Journal of Functional Biomaterials

16 pages, 12385 KiB

Open AccessEditor’s ChoiceArticle

Development of Neovasculature in Axially Vascularized Calcium Phosphate Cement Scaffolds

by Yassine Ouhaddi, Baptiste Charbonnier, Juliette Porge, Yu-Ling Zhang, Isadora Garcia, Uwe Gbureck, Liam Grover, Mirko Gilardino, Edward Harvey, Nicholas Makhoul and Jake Barralet

J. Funct. Biomater. 2023, 14(2), 105; https://doi.org/10.3390/jfb14020105 - 14 Feb 2023

Viewed by 2415

Abstract

Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical [...] Read more.

Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7–3 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1β expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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24 pages, 15394 KiB

Open AccessEditor’s ChoiceArticle

Metal–Peptide Complexes with Antimicrobial Potential for Cotton Fiber Protection

by Stela Georgieva, Petar Todorov, Desislava Staneva, Petar Grozdanov, Ivanka Nikolova and Ivo Grabchev

J. Funct. Biomater. 2023, 14(2), 106; https://doi.org/10.3390/jfb14020106 - 14 Feb 2023

Cited by 6 | Viewed by 2409

Abstract

A study of the formation of copper (II) complexes with hemorphin peptide motifs in alkalic water solutions is presented. The effect of the peptide ligand on the complexing properties of the Cu (II) ion was quantified by giving the stoichiometry and stability of [...] Read more.

A study of the formation of copper (II) complexes with hemorphin peptide motifs in alkalic water solutions is presented. The effect of the peptide ligand on the complexing properties of the Cu (II) ion was quantified by giving the stoichiometry and stability of the complex compounds in the medium in which they are formed using voltammetric (cyclic) and spectral (UV-Vis and fluorimetric) analytical techniques. The resulting complexes were examined via IR spectroscopy to detect M-N and M-O oscillations and using the EPR approach in solution and in the solid phase to view the coordination and ligand binding regime. The possibility of the synergistic action of copper ions in the antivirus protection processes of cotton fibers coated in the same solvent with the newly obtained complex compounds was also investigated. One of the advantages is the formation of the complexes in an environment where the immobilization takes place, which contributes to increasing the efficiency of the process. The obtained results may serve as an aid for future more detailed biological studies of structure–activity relationships (SARs). Full article

(This article belongs to the Special Issue Antibacterial, Antimicrobial and Antioxidant Properties of Biomaterials Derived from Peptides and Peptoids)

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17 pages, 5009 KiB

Open AccessEditor’s ChoiceReview

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

by Aurelio Salerno and Paolo Antonio Netti

J. Funct. Biomater. 2023, 14(2), 101; https://doi.org/10.3390/jfb14020101 - 13 Feb 2023

Cited by 11 | Viewed by 3546

Abstract

Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among [...] Read more.

Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among these strategies, emerging computer aided design and manufacturing processes, such as modular tissue unit patterning, promise to provide unprecedented control over the generation of biologically and biomechanically competent tissue analogues. This review discusses recent studies and highlights the role of scaffold microstructural properties and their drug release capability in cell fate control and tissue morphogenesis. Furthermore, the work highlights recent advances in the bottom-up fabrication of porous scaffolds and hybrid constructs through the computer-aided assembly of cell-free and/or cell-laden micro-modules. The advantages, current limitations, and future challenges of these strategies are described and discussed. Full article

(This article belongs to the Special Issue Multifunctional Bio-Scaffolds for Cell Growth and Tissue Morphogenesis)

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27 pages, 7113 KiB

Open AccessEditor’s ChoiceArticle

The Local Release of Teriparatide Incorporated in 45S5 Bioglass Promotes a Beneficial Effect on Osteogenic Cells and Bone Repair in Calvarial Defects in Ovariectomized Rats

by Juliani Caroline Ribeiro de Araújo, Leonardo Alvares Sobral Silva, Vinicius Almeida de Barros Lima, Tiago Moreira Bastos Campos, Paulo Noronha Lisboa Filho, Roberta Okamoto and Luana Marotta Reis de Vasconcellos

J. Funct. Biomater. 2023, 14(2), 93; https://doi.org/10.3390/jfb14020093 - 9 Feb 2023

Cited by 5 | Viewed by 2683

Abstract

With the increase in the population’s life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. [...] Read more.

With the increase in the population’s life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups (p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide. Full article

(This article belongs to the Special Issue Bone Regeneration and Repair Materials)

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20 pages, 4165 KiB

Open AccessEditor’s ChoiceArticle

Surface Modified β-Ti-18Mo-6Nb-5Ta (wt%) Alloy for Bone Implant Applications: Composite Characterization and Cytocompatibility Assessment

by Michael Escobar, Oriol Careta, Nora Fernández Navas, Aleksandra Bartkowska, Ludovico Andrea Alberta, Jordina Fornell, Pau Solsona, Thomas Gemming, Annett Gebert, Elena Ibáñez, Andreu Blanquer, Carme Nogués, Jordi Sort and Eva Pellicer

J. Funct. Biomater. 2023, 14(2), 94; https://doi.org/10.3390/jfb14020094 - 9 Feb 2023

Cited by 4 | Viewed by 2528

Abstract

Commercially available titanium alloys such as Ti-6Al-4V are established in clinical use as load-bearing bone implant materials. However, concerns about the toxic effects of vanadium and aluminum have prompted the development of Al- and V-free β-Ti alloys. Herein, a new alloy composed of [...] Read more.

Commercially available titanium alloys such as Ti-6Al-4V are established in clinical use as load-bearing bone implant materials. However, concerns about the toxic effects of vanadium and aluminum have prompted the development of Al- and V-free β-Ti alloys. Herein, a new alloy composed of non-toxic elements, namely Ti-18Mo-6Nb-5Ta (wt%), has been fabricated by arc melting. The resulting single β-phase alloy shows improved mechanical properties (Young’s modulus and hardness) and similar corrosion behavior in simulated body fluid when compared with commercial Ti-6Al-4V. To increase the cell proliferation capability of the new biomaterial, the surface of Ti-18Mo-6Nb-5Ta was modified by electrodepositing calcium phosphate (CaP) ceramic layers. Coatings with a Ca/P ratio of 1.47 were obtained at pulse current densities, −j_c, of 1.8–8.2 mA/cm², followed by 48 h of NaOH post-treatment. The thickness of the coatings has been measured by scanning electron microscopy from an ion beam cut, resulting in an average thickness of about 5 μm. Finally, cytocompatibility and cell adhesion have been evaluated using the osteosarcoma cell line Saos-2, demonstrating good biocompatibility and enhanced cell proliferation on the CaP-modified Ti-18Mo-6Nb-5Ta material compared with the bare alloy, even outperforming their CaP-modified Ti-6-Al-4V counterparts. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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15 pages, 15642 KiB

Open AccessEditor’s ChoiceArticle

3D-Printed GelMA/PEGDA/F127DA Scaffolds for Bone Regeneration

by Jianpeng Gao, Ming Li, Junyao Cheng, Xiao Liu, Zhongyang Liu, Jianheng Liu and Peifu Tang

J. Funct. Biomater. 2023, 14(2), 96; https://doi.org/10.3390/jfb14020096 - 9 Feb 2023

Cited by 39 | Viewed by 6871

Abstract

Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution [...] Read more.

Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution and gentle printing process. As commonly used bioinks, synthetic polymers such as polyethylene glycol diacrylate (PEGDA) and Pluronic F127 diacrylate (F127DA) have satisfactory printability and mechanical properties but usually lack sufficient adhesion to cells and tissues. Here, a compound BTE scaffold based on PEGDA, F127DA, and gelatin methacrylate (GelMA) was successfully prepared using DLP printing technology. The scaffold not only facilitated the adhesion and proliferation of cells, but also effectively promoted the osteogenic differentiation of mesenchymal stem cells in an osteoinductive environment. Moreover, the bone tissue volume/total tissue volume (BV/TV) of the GelMA/PEGDA/F127DA (GPF) scaffold in vivo was 49.75 ± 8.50%, higher than the value of 37.10 ± 7.27% for the PEGDA/F127DA (PF) scaffold and 20.43 ± 2.08% for the blank group. Therefore, the GPF scaffold prepared using DLP printing technology provides a new approach to the treatment of bone defects. Full article

(This article belongs to the Special Issue Bone Regeneration and Repair Materials)

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14 pages, 1948 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Surface Treatments on Zirconia Bond Strength and Durability

by Dongni Shen, Huihua Wang, Ying Shi, Zhiwei Su, Matthias Hannig and Baiping Fu

J. Funct. Biomater. 2023, 14(2), 89; https://doi.org/10.3390/jfb14020089 - 7 Feb 2023

Cited by 18 | Viewed by 4966

Abstract

To evaluate the effects of airborne particle abrasion (APA) combined with MDP-containing resin cement, a glass-ceramic spray deposition (GCSD) method on the shear bond strengths (SBSs) and durability of 3 mol% yttrium oxide-stabilized zirconia ceramic (3Y-TZP) compared with lithium disilicate glass ceramics (LDGC). [...] Read more.

To evaluate the effects of airborne particle abrasion (APA) combined with MDP-containing resin cement, a glass-ceramic spray deposition (GCSD) method on the shear bond strengths (SBSs) and durability of 3 mol% yttrium oxide-stabilized zirconia ceramic (3Y-TZP) compared with lithium disilicate glass ceramics (LDGC). 3Y-TZP disks were randomly treated as follows: for Group APA+MDP, 3Y-TZP was abrased using 50 μm Al₂O₃ particles under 0.1 Mpa and bonded with MDP-containing resin cement; for Group GCSD, 3Y-TZP was treated with the GCSD method, etched by 5% HF for 90 s, silanized and bonded with resin cement without MDP. Group LDGC was bonded as the Group GCSD. X-ray diffraction (XRD), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive X-ray detector (EDX) were used to analyze the surface chemical and micro-morphological changes of the ceramics before bonding. The bonded ceramic specimens were randomly divided into subgroups, and the SBSs were determined before and after 10,000 thermocycling. The SBSs were analyzed with a one-way ANOVA analysis. Failure modes were determined with optical microscopy and SEM. The XRD, ATR-FTIR and XPS results identified the formation of lithium disilicate and zirconium silicate on 3Y-TZP after GCSD. The SEM micrographs revealed that 3Y-TZP surfaces were roughened by APA, while 3Y-TZP with GCSD and LDGC surfaces could be etched by HF to be porous. The APA treatment combined with MDP-containing resin cement produced the high immediate zirconia shear bond strengths (SBSs: 37.41 ± 13.51 Mpa) that was similar to the SBSs of the LDGC (34.87 ± 11.02 Mpa, p > 0.05), but, after thermocycling, the former dramatically decreased (24.00 ± 6.86 Mpa, maximum reduction by 35.85%) and the latter exhibited the highest SBSs (30.72 ± 7.97 Mpa, minimum reduction by 11.9%). The 3Y-TZP with GCSD treatment displayed the lower zirconia SBSs before thermocycling (27.03 ± 9.76 Mpa, p < 0.05), but it was similar to the 3Y-TZP treated with APA and MDP containing resin cement after thermocycling (21.84 ± 7.03 vs. 24.00 ± 6.86 Mpa, p > 0.05). The APA combined with MDP-containing resin cement could achieve the high immediate zirconia SBSs of those of the LDGC, but it decreased significantly after thermocycling. The GCSD technique could yield the immediate zirconia SBSs similar to those of LDGC before thermocycling, and long-term zirconia SBSs were similar to those of 3Y-TZP treated with APA followed by MDP-containing resin cement after thermocycling. Hence, the GCSD technique could enrich zirconia surface treatments and is an alternative to zirconia surface pretreatment for 3Y-TZP bond durability. Full article

(This article belongs to the Section Dental Biomaterials)

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18 pages, 3148 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Silk–Inorganic Nanoparticle Hybrid Hydrogel as an Injectable Bone Repairing Biomaterial

by Liangyan Sun, Minqi Lu, Ling Chen, Bingjiao Zhao, Jinrong Yao, Zhengzhong Shao, Xin Chen and Yuehua Liu

J. Funct. Biomater. 2023, 14(2), 86; https://doi.org/10.3390/jfb14020086 - 2 Feb 2023

Cited by 13 | Viewed by 3218

Abstract

Silk fibroin is regarded as a promising biomaterial in various areas, including bone tissue regeneration. Herein, Laponite^® (LAP), which can promote osteogenic differentiation, was introduced into regenerated silk fibroin (RSF) to prepare an RSF/LAP hybrid hydrogel. This thixotropic hydrogel is injectable during [...] Read more.

Silk fibroin is regarded as a promising biomaterial in various areas, including bone tissue regeneration. Herein, Laponite^® (LAP), which can promote osteogenic differentiation, was introduced into regenerated silk fibroin (RSF) to prepare an RSF/LAP hybrid hydrogel. This thixotropic hydrogel is injectable during the operation process, which is favorable for repairing bone defects. Our previous work demonstrated that the RSF/LAP hydrogel greatly promoted the osteogenic differentiation of osteoblasts in vitro. In the present study, the RSF/LAP hydrogel was found to have excellent biocompatibility and significantly improved new bone formation in a standard rat calvarial defect model in vivo. Additionally, the underlying biological mechanism of the RSF/LAP hydrogel in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was extensively explored. The results indicate that the RSF/LAP hydrogels provide suitable conditions for the adhesion and proliferation of BMSCs, showing good biocompatibility in vitro. With the increase in LAP content, the alkaline phosphatase (ALP) activity and mRNA and protein expression of the osteogenic markers of BMSCs improved significantly. Protein kinase B (AKT) pathway activation was found to be responsible for the inherent osteogenic properties of the RSF/LAP hybrid hydrogel. Therefore, the results shown in this study firmly suggest such an injectable RSF/LAP hydrogel with good biocompatibility (both in vitro and in vivo) would have good application prospects in the field of bone regeneration. Full article

(This article belongs to the Section Bone Biomaterials)

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14 pages, 4532 KiB

Open AccessEditor’s ChoiceArticle

Thermal Behavior of Graphene Oxide Deposited on 3D-Printed Polylactic Acid for Photothermal Therapy: An Experimental–Numerical Analysis

by Jesús Vence, Christian Gil, Laura González-Rodríguez and Miriam López-Álvarez

J. Funct. Biomater. 2023, 14(2), 80; https://doi.org/10.3390/jfb14020080 - 31 Jan 2023

Cited by 5 | Viewed by 2350

Abstract

The present work evaluates the thermal behavior of graphene oxide (GO) when deposited on 3D-printed polylactic acid (PLA), in order to develop a medical device for photothermal therapy applications. An experimental–numerical analysis was performed to assess the photothermal conversion capacity, based on the [...] Read more.

The present work evaluates the thermal behavior of graphene oxide (GO) when deposited on 3D-printed polylactic acid (PLA), in order to develop a medical device for photothermal therapy applications. An experimental–numerical analysis was performed to assess the photothermal conversion capacity, based on the power emitted by a NIR (785 nm) laser, and the subsequent temperature distribution on the GO-PLA material. The influence of the deposited mass of GO and the PLA thickness was studied through 40 different scenarios. The results estimated a value of photothermal conversion efficiency of up to 32.6%, achieved for the lower laser power density that was tested (0.335 mW/mm²), and a high mass value of deposited GO (1.024 × 10⁻³ mg/mm²). In fact, an optimal mass of GO in the range of 1.024–2.048 × 10⁻³ mg/mm² is proposed, in terms of absorption capacity, since a higher mass of GO would not increase the conversion efficiency. Moreover, the study allowed for an estimation of the thermal conductivity of this specific biomaterial (0.064 W/m·K), and proved that a proper combination of GO mass, PLA thickness, and laser power can induce ablative (>60 °C, in a concentrated area), moderate (50 °C), and mild (43 °C) hyperthermia on the bottom face of the biomaterial. Full article

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14 pages, 1669 KiB

Open AccessEditor’s ChoiceArticle

Hyaluronic Acid Hydrogel Containing Resveratrol-Loaded Chitosan Nanoparticles as an Adjuvant in Atopic Dermatitis Treatment

by Raffaele Conte, Ilenia De Luca, Anna Valentino, Pierfrancesco Cerruti, Parisa Pedram, Gustavo Cabrera-Barjas, Arash Moeini and Anna Calarco

J. Funct. Biomater. 2023, 14(2), 82; https://doi.org/10.3390/jfb14020082 - 31 Jan 2023

Cited by 38 | Viewed by 5671

Abstract

Atopic dermatitis (AD) is a common disease-causing skin inflammation, redness, and irritation, which can eventually result in infection that drastically impacts patient quality of life. Resveratrol (Res) is a natural phytochemical famed for its excellent anti-inflammatory and antioxidant activities. However, it is poorly [...] Read more.

Atopic dermatitis (AD) is a common disease-causing skin inflammation, redness, and irritation, which can eventually result in infection that drastically impacts patient quality of life. Resveratrol (Res) is a natural phytochemical famed for its excellent anti-inflammatory and antioxidant activities. However, it is poorly bioavailable. Thus, a drug delivery system is needed to enhance in vivo bioactivity. Herein, we report the preparation of hyaluronic acid (HA) hydrogels containing resveratrol-loaded chitosan (CS) nanoparticles, their physicochemical analysis, and their potential therapeutic effects in the treatment of AD. Positively charged CS nanoparticles prepared by tripolyphosphate (TPP) gelation showed sizes ranging from 120 to around 500 nm and Res encapsulation efficiency as high as 80%. Embedding the nanoparticles in HA retarded their hydrolytic degradation and also slowed resveratrol release. Resveratrol released from nanoparticle-loaded hydrogel counteracted the oxidative damage induced by ROS generation in TNF-α/INF-γ-treated human keratinocytes (HaCaT) used as an AD in vitro model. Moreover, pre-treatment with Res@gel reduced secretion and gene expression of proinflammatory cytokines in HaCaT cells. The physicochemical analysis and in vitro assay confirmed that the formulated hydrogel could be considered an efficient and sustained resveratrol delivery vector in AD treatment. Full article

(This article belongs to the Special Issue High Performance Functional Bio-Based Polymers for Skin-Contact Products (Volume 2))

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20 pages, 3756 KiB

Open AccessEditor’s ChoiceArticle

Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography

by Paola Gomes Souza, Leticia Faustino Adolpho, Helena Bacha Lopes, Denise Weffort, Alann Thaffarell Portilho Souza, Fabiola Singaretti Oliveira, Adalberto Luiz Rosa and Marcio Mateus Beloti

J. Funct. Biomater. 2023, 14(2), 79; https://doi.org/10.3390/jfb14020079 - 30 Jan 2023

Cited by 8 | Viewed by 2432

Abstract

Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H₂ [...] Read more.

Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H₂SO₄/H₂O₂. Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. Results: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. Conclusion: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces. Full article

(This article belongs to the Special Issue Bone Regeneration and Repair Materials)

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23 pages, 4643 KiB

Open AccessEditor’s ChoiceArticle

Bioactive Synthetic Polymer-Based Polyelectrolyte LbL Coating Assembly on Surface Treated AZ31-Mg Alloys

by Sangeetha Kunjukunju, Abhijit Roy, John Ohodnicki, Boeun Lee, Joe E. Candiello, Mitali Patil and Prashant N. Kumta

J. Funct. Biomater. 2023, 14(2), 75; https://doi.org/10.3390/jfb14020075 - 29 Jan 2023

Cited by 2 | Viewed by 2750

Abstract

Polyelectrolyte layer-by-layer (LbL) films on pretreated Mg containing 3 wt.% Al and 1 wt.% Zn (MgAZ31) alloy surfaces were prepared under physiological conditions offering improved bioresponse and corrosive protection. Pretreatments of the model MgAZ31 substrate surfaces were performed by alkaline and fluoride coating [...] Read more.

Polyelectrolyte layer-by-layer (LbL) films on pretreated Mg containing 3 wt.% Al and 1 wt.% Zn (MgAZ31) alloy surfaces were prepared under physiological conditions offering improved bioresponse and corrosive protection. Pretreatments of the model MgAZ31 substrate surfaces were performed by alkaline and fluoride coating methods. The anti-corrosion and cytocompatibility behavior of pretreated substrates were evaluated. The LbL film assembly consisted of an initial layer of polyethyleneimine (PEI), followed by alternate layers of poly (lactic-co-glycolic acid) (PLGA) and poly (allylamine hydrochloride) (PAH), which self-arrange via electrostatic interactions on the pretreated MgAZ31 alloy substrate surface. The physicochemical characterization, surface morphologies, and microstructures of the LbL films were investigated using Fourier-transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The in vitro stability studies related to the LbL coatings confirmed that the surface treatments are imperative to achieve the lasting stability of PLGA/PAH layers. Electrochemical impedance spectroscopy measurements demonstrated that pretreated and LbL multilayered coated substrates enhanced the corrosion resistance of the bare MgAZ31 alloy. Cytocompatibility studies using human mesenchymal stem cells seeded directly over the substrates showed that the pretreated and LbL-generated surfaces were more cytocompatible, displaying reduced cytotoxicity than the bare MgAZ31. The release of bovine serum albumin protein from the LbL films was also studied. The initial data presented cooperatively demonstrate the promise of creating LbL layers on Mg-related bioresorbable scaffolds to obtain improved surface bio-related activity. Full article

(This article belongs to the Special Issue Women in Science: Functional Biomaterials)

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15 pages, 6576 KiB

Open AccessEditor’s ChoiceArticle

Developing a Novel Enamel Adhesive with Amorphous Calcium Phosphate and Silver Nanoparticles to Prevent Demineralization during Orthodontic Treatment

by Ao Jia, Pei Wang, Fei Tong, Ziqiang Chen, Yunyun Deng, Haiyan Yao, Lianguo Wang, Yifan Liu and Hongshan Ge

J. Funct. Biomater. 2023, 14(2), 77; https://doi.org/10.3390/jfb14020077 - 29 Jan 2023

Cited by 9 | Viewed by 2761

Abstract

During fixed orthodontic treatment, white spot lesions are prevalent issues associated with cariogenic bacteria. This study aims to construct an orthodontic adhesive containing nanoparticles of amorphous calcium phosphate-polydopamine-Ag (NPA) fillers to combat white spot lesions. The NPA fillers were prepared and characterized by [...] Read more.

During fixed orthodontic treatment, white spot lesions are prevalent issues associated with cariogenic bacteria. This study aims to construct an orthodontic adhesive containing nanoparticles of amorphous calcium phosphate-polydopamine-Ag (NPA) fillers to combat white spot lesions. The NPA fillers were prepared and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The biocompatibility of the fillers was evaluated. A colony counting test evaluated the antibacterial property of the fillers against Streptococcus mutans (S. mutans). NPA fillers were mixed with orthodontic adhesive (Transbond XT) at different weight ratios (0, 0.1, 0.2, 0.3, and 0.5 wt.%). The shear bond strength and antibacterial properties were then further investigated. The results showed that NPA was prepared successfully, with good antibacterial properties. The cell survival rate of all groups of fillers was higher than 70%, showing good biocompatibility. Moreover, the shear bond strength of the orthodontic adhesive with 0.2 wt.% NPA fillers was 11.89 ± 1.27 MPa, meeting the minimal clinical bond strength requirements of 7.8 MPa. Furthermore, the orthodontic adhesive resin blocks and the extract displayed good antibacterial properties, with the number of colonies decreasing significantly (p < 0.001). Taken together, we think that an orthodontic adhesive with NPA may have a good application potential for the prevention and treatment of white spot lesions. Full article

(This article belongs to the Special Issue Bioactive Coatings and Surfaces for Medical Applications)

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10 pages, 1380 KiB

Open AccessEditor’s ChoiceArticle

Magnetic Response of Nano/Microparticles into Elastomeric Electrospun Fibers

by Vincenzo Iannotti, Giovanni Ausanio, Anna M. Ferretti, Zaheer Ud Din Babar, Vincenzo Guarino, Luigi Ambrosio and Luciano Lanotte

J. Funct. Biomater. 2023, 14(2), 78; https://doi.org/10.3390/jfb14020078 - 29 Jan 2023

Cited by 5 | Viewed by 2306

Abstract

Combining magnetic nanoparticles (MNPs) with high-voltage processes to produce ultra-thin magnetic nanofibers (MNFs) fosters the development of next-generation technologies. In this study, polycarbonate urethane nanofibers incorporating magnetic particles were produced via the electrospinning technique. Two distinct types of magnetic payload were used: (a) [...] Read more.

Combining magnetic nanoparticles (MNPs) with high-voltage processes to produce ultra-thin magnetic nanofibers (MNFs) fosters the development of next-generation technologies. In this study, polycarbonate urethane nanofibers incorporating magnetic particles were produced via the electrospinning technique. Two distinct types of magnetic payload were used: (a) iron oxide nanoparticles (IONPs) with an average size and polydispersity index of 7.2 nm and 3.3%, respectively; (b) nickel particles (NiPs) exhibiting a bimodal size distribution with average sizes of 129 nanometers and 600 nanometers, respectively, and corresponding polydispersity indexes of 27.8% and 3.9%. Due to varying particle sizes, significant differences were observed in their aggregation and distribution within the nanofibers. Further, the magnetic response of the IONP and/or NiP-loaded fiber mats was consistent with their morphology and polydispersity index. In the case of IONPs, the remanence ratio (M_r/M_s) and the coercive field (H_c) were found to be zero, which agrees with their superparamagnetic behavior when the average size is smaller than 20–30 nm. However, the NiPs show M_r/M_s = 22% with a coercive field of 0.2kOe as expected for particles in a single or pseudo-single domain state interacting with each other via dipolar interaction. We conclude that magnetic properties can be modulated by controlling the average size and polydispersity index of the magnetic particles embedded in fiber mats to design magneto-active systems suitable for different applications (i.e., wound healing and drug delivery). Full article

(This article belongs to the Special Issue State-of-the-Art Functional Biomaterials in Italy)

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14 pages, 4070 KiB

Open AccessEditor’s ChoiceArticle

Chitosan/Phenolic Compounds Scaffolds for Connective Tissue Regeneration

by Beata Kaczmarek-Szczepańska, Izabela Polkowska, Katarzyna Paździor-Czapula, Beata Nowicka, Magdalena Gierszewska, Marta Michalska-Sionkowska and Iwona Otrocka-Domagała

J. Funct. Biomater. 2023, 14(2), 69; https://doi.org/10.3390/jfb14020069 - 28 Jan 2023

Cited by 7 | Viewed by 2938

Abstract

Chitosan-based scaffolds modified by gallic acid, ferulic acid, and tannic acid were fabricated. The aim of the experiment was to compare the compatibility of scaffolds based on chitosan with gallic acid, ferulic acid, or tannic acid using the in vivo method. For this [...] Read more.

Chitosan-based scaffolds modified by gallic acid, ferulic acid, and tannic acid were fabricated. The aim of the experiment was to compare the compatibility of scaffolds based on chitosan with gallic acid, ferulic acid, or tannic acid using the in vivo method. For this purpose, materials were implanted into rabbits in the middle of the latissimus dorsi muscle length. A scaffold based on unmodified chitosan was implanted by the same method as a control. Moreover, the Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) spectra and scanning electron microscope (SEM) observations were made to study the interactions between chitosan and phenolic acids. Additionally, antioxidant properties and blood compatibility were investigated. The results showed that all studied materials were safe and non-toxic. However, chitosan scaffolds modified by gallic acid and tannic acid were resorbed faster and, as a result, tissues were organized faster than those modified by ferulic acid or unmodified. Full article

(This article belongs to the Special Issue Tannins and Other Polyphenols as Functional Biomaterials)

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16 pages, 5413 KiB

Open AccessEditor’s ChoiceArticle

Effect of the Combination of Torsional and Tensile Stress on Corrosion Behaviors of Biodegradable WE43 Alloy in Simulated Body Fluid

by Bowen Wang, Wei Gao, Chao Pan, Debao Liu and Xiaohao Sun

J. Funct. Biomater. 2023, 14(2), 71; https://doi.org/10.3390/jfb14020071 - 28 Jan 2023

Cited by 10 | Viewed by 2640

Abstract

The real physiological environment of the human body is complicated, with different degrees and forms of loads applied to biomedical implants caused by the daily life of the patients, which will definitely influence the degradation behaviors of Mg-based biodegradable implants. In the present [...] Read more.

The real physiological environment of the human body is complicated, with different degrees and forms of loads applied to biomedical implants caused by the daily life of the patients, which will definitely influence the degradation behaviors of Mg-based biodegradable implants. In the present study, the degradation behaviors of modified WE43 alloys under the combination of torsional and tensile stress were systematically investigated. Slow strain rate tensile tests revealed that the simulated body fluid (SBF) solution could deteriorate the ultimate tensile stress of WE43 alloy from 210.1 MPa to 169.2 MPa. In the meantime, the fracture surface of the specimens tested in the SBF showed an intergranular corrosion morphology in the marginal region, while the central area appeared not to have been affected by the corrosive media. The bio-degradation performances under the combination of torsional and tensile stressed conditions were much more severe than those under unstressed conditions or single tensile stressed situations. The combination of 40 MPa tensile and 40 MPa torsional stress resulted in a degradation rate over 20 mm/y, which was much higher than those under 80 MPa single tensile stress (4.5 mm/y) or 80 MPa single torsional stress (13.1 mm/y). The dynamic formation and destruction mechanism of the protective corrosion products film on the modified WE43 alloy could attribute to the exacerbated degradation performance and the unique corrosion morphology. The dynamic environment and multi-directional loading could severely accelerate the degradation process of modified WE43 alloy. Therefore, the SCC susceptibility derived from a single directional test may be not suitable for practical purposes. Complex external stress was necessary to simulate the in vivo environment for the development of biodegradable Mg-based implants for clinical applications. Full article

(This article belongs to the Special Issue Corrosion Science in Biodegradable Implants)

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14 pages, 8010 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Differences between the Fittings of Dental Prostheses Produced by CAD-CAM and Laser Sintering Processes

by Mariano Herrero-Climent, Miquel Punset, Meritxell Molmeneu, Aritza Brizuela and Javier Gil

J. Funct. Biomater. 2023, 14(2), 67; https://doi.org/10.3390/jfb14020067 - 26 Jan 2023

Cited by 2 | Viewed by 2283

Abstract

Digital dentistry and new techniques for the dental protheses’ suprastructure fabrication have undergone a great evolution in recent years, revolutionizing the quality of dental prostheses. The aim of this work is to determine whether the best horizontal marginal fit is provided by the [...] Read more.

Digital dentistry and new techniques for the dental protheses’ suprastructure fabrication have undergone a great evolution in recent years, revolutionizing the quality of dental prostheses. The aim of this work is to determine whether the best horizontal marginal fit is provided by the CAD-CAM technique or by laser sintering. These values have been compared with the traditional casting technique. A total of 30 CAD-CAM models, 30 laser sintering models, and 10 casting models (as control) were fabricated. The structures realized with chromium–cobalt (CrCo) have been made by six different companies, always with the same model. Scanning electron microscopy with a high-precision image analysis system was used, and 10,000 measurements were taken for each model on the gingival (external) and palatal (internal) side. Thus, a total of 1,400,000 images were measured. It was determined that the CAD-CAM technique is the one that allows the best adjustments in the manufacturing methods studied. The laser sintering technique presents less adjustment, showing the presence of porosities and volume contraction defects due to solidification processes and heterogeneities in the chemical composition (coring). The technique with the worst adjustments is the casting technique, containing numerous defects in the suprastructure. The statistical analysis of results reflected the presence of statistically significant gap differences between the three manufacturing methods analyzed (p < 0.05), with the samples manufactured by CAD-CAM and by traditional casting processes being the ones that showed lower and higher values, respectively. No statistically significant differences in fit were observed between the palatal and gingival fit values, regardless of the manufacturing method used. No statistically significant differences in adjustment between the different manufacturing centers were found, regardless of the process used. Full article

(This article belongs to the Special Issue Biomaterials in Restorative Dentistry and Endodontics)

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17 pages, 7346 KiB

Open AccessEditor’s ChoiceArticle

Ciprofloxacin Release and Corrosion Behaviour of a Hybrid PEO/PCL Coating on Mg3Zn0.4Ca Alloy

by Lara Moreno, Cheng Wang, Sviatlana V. Lamaka, Mikhail L. Zheludkevich, Juan Rodríguez-Hernández, Raul Arrabal and Endzhe Matykina

J. Funct. Biomater. 2023, 14(2), 65; https://doi.org/10.3390/jfb14020065 - 25 Jan 2023

Cited by 17 | Viewed by 2639

Abstract

In the present work, a hybrid hierarchical coating (HHC) system comprising a plasma electrolytic oxidation (PEO) coating and a homogeneously porous structured polycaprolactone (PCL) top-coat layer, loaded with ciprofloxacin (CIP), was developed on Mg3Zn0.4Ca alloy. According to the findings, the HHC system avoided [...] Read more.

In the present work, a hybrid hierarchical coating (HHC) system comprising a plasma electrolytic oxidation (PEO) coating and a homogeneously porous structured polycaprolactone (PCL) top-coat layer, loaded with ciprofloxacin (CIP), was developed on Mg3Zn0.4Ca alloy. According to the findings, the HHC system avoided burst release and ensured gradual drug elution (64% over 240 h). The multi-level protection of the magnesium alloy is achieved through sealing of the PEO coating pores by the polymer layer and the inhibiting effect of CIP (up to 74%). The corrosion inhibition effect of HHC and the eluted drug is associated with the formation of insoluble CIP-Me (Mg/Ca) chelates that repair the defects in the HHC and impede the access of corrosive species as corroborated by FTIR spectra, EIS and SEM images after 24 h of immersion. Therefore, CIP participates in an active protection mechanism by interacting with cations coming through the damaged coating. Full article

(This article belongs to the Special Issue Advances in Biomaterials Engineering)

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19 pages, 12463 KiB

Open AccessEditor’s ChoiceArticle

Effect of Heat Treatment on Osteoblast Performance and Bactericidal Behavior of Ti6Al4V(ELI)-3at.%Cu Fabricated by Laser Powder Bed Fusion

by Anna Martín Vilardell, Vanesa Cantillo Alzamora, Luana Vittoria Bauso, Cristina Madrid, Pavel Krakhmalev, Mihaela Albu, Ina Yadroitsava, Igor Yadroitsev and Natalia Garcia-Giralt

J. Funct. Biomater. 2023, 14(2), 63; https://doi.org/10.3390/jfb14020063 - 23 Jan 2023

Cited by 6 | Viewed by 2535

Abstract

Cu addition to alloys for biomedical applications has been of great interest to reduce bacterial growth. In situ-alloyed Ti6Al4V(ELI)-3at.%Cu was successfully manufactured by laser powder bed fusion (L-PBF). Even so, post-heat treatments are required to avoid distortions and/or achieve required/desired mechanical and fatigue [...] Read more.

Cu addition to alloys for biomedical applications has been of great interest to reduce bacterial growth. In situ-alloyed Ti6Al4V(ELI)-3at.%Cu was successfully manufactured by laser powder bed fusion (L-PBF). Even so, post-heat treatments are required to avoid distortions and/or achieve required/desired mechanical and fatigue properties. The present study is focused on the investigation of microstructural changes in L-PBF Ti6Al4V(ELI)-3at.%Cu after stress relieving and annealing treatments, as well as their influence on osteoblast and bactericidal behavior. After the stress relieving treatment, a homogenously distributed β phase and CuTi₂ intermetallic precipitates were observed over the αʹ matrix. The annealing treatment led to the increase in amount and size of both types of precipitates, but also to phase redistribution along α lamellas. Although microstructural changes were not statistically significant, such increase in β and CuTi₂ content resulted in an increase in osteoblast proliferation after 14 days of cell culture. A significant bactericidal behavior of L-PBF Ti6Al4V(ELI)-3at.%Cu by means of ion release was found after the annealing treatment, provably due to the easier release of Cu ions from β phase. Biofilm formation was inhibited in all on Cu-alloyed specimens with stress relieving but also annealing treatment. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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16 pages, 3289 KiB

Open AccessEditor’s ChoiceArticle

Amelogenin-Derived Peptide (ADP-5) Hydrogel for Periodontal Regeneration: An In Vitro Study on Periodontal Cells Cytocompatibility, Remineralization and Inflammatory Profile

by Nina Attik, Xavier Garric, Audrey Bethry, Gilles Subra, Charlène Chevalier, Brahim Bouzouma, Pascal Verdié, Brigitte Grosgogeat and Kerstin Gritsch

J. Funct. Biomater. 2023, 14(2), 53; https://doi.org/10.3390/jfb14020053 - 18 Jan 2023

Cited by 6 | Viewed by 3084

Abstract

A relevant alternative to enamel matrix derivatives from animal origin could be the use of synthetic amelogenin-derived peptides. This study aimed to assess the effect of a synthetic amelogenin-derived peptide (ADP-5), alone or included in an experimental gellan–xanthan hydrogel, on periodontal cell behavior [...] Read more.

A relevant alternative to enamel matrix derivatives from animal origin could be the use of synthetic amelogenin-derived peptides. This study aimed to assess the effect of a synthetic amelogenin-derived peptide (ADP-5), alone or included in an experimental gellan–xanthan hydrogel, on periodontal cell behavior (gingival fibroblasts, periodontal ligament cells, osteoblasts and cementoblasts). The effect of ADP-5 (50, 100, and 200 µg/mL) on cell metabolic activity was examined using Alamar blue assay, and cell morphology was assessed by confocal imaging. An experimental gellan–xanthan hydrogel was then designed as carrier for ADP-5 and compared to the commercial gel Emdogain^®. Alizarin Red was used to determine the periodontal ligament and cementoblasts cell mineralization. The inflammatory profile of these two cells was also quantified using ELISA (vascular endothelial growth factor A, tumor necrosis factor α, and interleukin 11) mediators. ADP-5 enhanced cell proliferation and remineralization; the 100 µg/mL concentration was more efficient than 50 and 200 µg/mL. The ADP-5 experimental hydrogel exhibited equivalent good biological behavior compared to Emdogain^® in terms of cell colonization, mineralization, and inflammatory profile. These findings revealed relevant insights regarding the ADP-5 biological behavior. From a clinical perspective, these outcomes could instigate the development of novel functionalized scaffold for periodontal regeneration. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Periodontal Regeneration)

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15 pages, 3998 KiB

Open AccessEditor’s ChoiceArticle

Gallium-Doped Hydroxyapatite Shows Antibacterial Activity against Pseudomonas aeruginosa without Affecting Cell Metabolic Activity

by Marika Mosina, Claudia Siverino, Liga Stipniece, Artemijs Sceglovs, Renats Vasiljevs, T. Fintan Moriarty and Janis Locs

J. Funct. Biomater. 2023, 14(2), 51; https://doi.org/10.3390/jfb14020051 - 17 Jan 2023

Cited by 12 | Viewed by 3198

Abstract

Calcium phosphates (CaPs) have been used in bone regeneration for decades. Among the described CaPs, synthetic hydroxyapatite (HAp) has a chemical composition similar to that of natural bone. Gallium-containing compounds have been studied since the 1970s for the treatment of autoimmune diseases and [...] Read more.

Calcium phosphates (CaPs) have been used in bone regeneration for decades. Among the described CaPs, synthetic hydroxyapatite (HAp) has a chemical composition similar to that of natural bone. Gallium-containing compounds have been studied since the 1970s for the treatment of autoimmune diseases and have shown beneficial properties, such as antibacterial activity and inhibition of osteoclast activity. In this study, we synthesized hydroxyapatite (HAp) powder with Ga doping ratios up to 6.9 ± 0.5 wt% using the wet chemical precipitation method. The obtained products were characterized using XRD, BET, FTIR, and ICP-MS. Ga³⁺ ion release was determined in the cell culture media for up to 30 days. Antibacterial activity was assessed against five bacterial species: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. The biocompatibility of the GaHAp samples was determined in human fibroblasts (hTERT-BJ1) through direct and indirect tests. The structure of the synthesized products was characteristic of HAp, as revealed with XRD and FTIR, although the addition of Ga caused a decrease in the crystallite size. Ga³⁺ was released from GaHAp paste in a steady manner, with approximately 40% being released within 21 days. GaHAp with the highest gallium contents, 5.5 ± 0.1 wt% and 6.9 ± 0.5 wt%, inhibited the growth of all five bacterial species, with the greatest activity being against Pseudomonas aeruginosa. Biocompatibility assays showed maintained cell viability (~80%) after seven days of indirect exposure to GaHAp. However, when GaHAp with Ga content above 3.3 ± 0.4 wt% was directly applied on the cells, a decrease in metabolic activity was observed on the seventh day. Overall, these results show that GaHAp with Ga content below 3.3 ± 0.4 wt% has attractive antimicrobial properties, without affecting the cell metabolic activity, creating a material that could be used for bone regeneration and prevention of infection. Full article

(This article belongs to the Special Issue Advances in Biomaterials Engineering)

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23 pages, 4995 KiB

Open AccessEditor’s ChoiceArticle

Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application

by Michael R. Arul, Changli Zhang, Ibtihal Alahmadi, Isaac L. Moss, Yeshavanth Kumar Banasavadi-Siddegowda, Sama Abdulmalik, Svenja Illien-Junger and Sangamesh G. Kumbar

J. Funct. Biomater. 2023, 14(2), 52; https://doi.org/10.3390/jfb14020052 - 17 Jan 2023

Cited by 7 | Viewed by 3350

Abstract

Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In [...] Read more.

Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150–162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections. Full article

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13 pages, 14495 KiB

Open AccessEditor’s ChoiceArticle

Acid-Triggered Release of Eugenol and Fluoride by Desensitizing Macro- and Nanoparticles

by Grigoriy Sereda, Abu Ahammadullah, Nisitha Wijewantha and Yulia Almiron Solano

J. Funct. Biomater. 2023, 14(1), 42; https://doi.org/10.3390/jfb14010042 - 11 Jan 2023

Cited by 2 | Viewed by 2908

Abstract

The modern dentifrice industry needs non-toxic materials able to adhere to dentin, occlude dentinal tubules, hold pharmacons at the surface of dentin, and release them on demand to the location the tooth needs them most. Novel dental materials loaded with eugenol or fluoride-ions [...] Read more.

The modern dentifrice industry needs non-toxic materials able to adhere to dentin, occlude dentinal tubules, hold pharmacons at the surface of dentin, and release them on demand to the location the tooth needs them most. Novel dental materials loaded with eugenol or fluoride-ions examined for the release of the pharmacon in an aqueous suspension efficiently adhere to the surface of human dentin and occlude dentinal tubules as evidenced by Scanning Electron Microscopy (SEM). Ultraviolet-visible (UV-vis) absorption spectroscopy and a fluoride-selective electrode quantified the release of pharmacons. The surface modification with casein stabilizes micro- and nanoparticles of calcium carbonate in aqueous suspensions, enabling their application in dentifrices. The ability of particles to hold and release eugenol depends on their morphology and composition, with the casein-coated calcium carbonate microspheres being the most acid-sensitive and most promising for dentifrice applications. The novel material releases fluoride under physiologically low pH, regardless of the presence of other ingredients of the artificial saliva, which sustains the bulk fluoride concentration comparable with most fluorinated toothpastes. Low pH-triggered release mechanisms selectively supply the drug to the areas that need it most, reducing the overall dose and ushering in a new type of targeted dentifrices. Full article

(This article belongs to the Special Issue State of the Art in Dental Materials)

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16 pages, 3046 KiB

Open AccessEditor’s ChoiceArticle

BMSCs-Seeded Interpenetrating Network GelMA/SF Composite Hydrogel for Articular Cartilage Repair

by Kaiwen Zheng, Xu Zheng, Mingzhao Yu, Yu He and Di Wu

J. Funct. Biomater. 2023, 14(1), 39; https://doi.org/10.3390/jfb14010039 - 10 Jan 2023

Cited by 17 | Viewed by 3452

Abstract

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel [...] Read more.

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration. Full article

(This article belongs to the Special Issue Advanced Functional Hydrogels for Tissue Engineering and Regenerative Medicine)

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39 pages, 74149 KiB

Open AccessEditor’s ChoiceArticle

Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices

by David Alexander Gregory, Annabelle T. R. Fricker, Peter Mitrev, Meghna Ray, Emmanuel Asare, Daniel Sim, Soponvit Larpnimitchai, Zixuan Zhang, Jinge Ma, Santosh S. V. Tetali and Ipsita Roy

J. Funct. Biomater. 2023, 14(1), 40; https://doi.org/10.3390/jfb14010040 - 10 Jan 2023

Cited by 27 | Viewed by 5227

Abstract

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits [...] Read more.

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used. Full article

(This article belongs to the Special Issue Biomaterials Sourced from Nature)

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14 pages, 3145 KiB

Open AccessEditor’s ChoiceArticle

Full Skin Equivalent Models for Simulation of Burn Wound Healing, Exploring Skin Regeneration and Cytokine Response

by Patrick P. G. Mulder, Rajiv S. Raktoe, Marcel Vlig, Anouk Elgersma, Esther Middelkoop and Bouke K. H. L. Boekema

J. Funct. Biomater. 2023, 14(1), 29; https://doi.org/10.3390/jfb14010029 - 4 Jan 2023

Cited by 4 | Viewed by 5100

Abstract

Healing of burn injury is a complex process that often leads to the development of functional and aesthetic complications. To study skin regeneration in more detail, organotypic skin models, such as full skin equivalents (FSEs) generated from dermal matrices, can be used. Here, [...] Read more.

Healing of burn injury is a complex process that often leads to the development of functional and aesthetic complications. To study skin regeneration in more detail, organotypic skin models, such as full skin equivalents (FSEs) generated from dermal matrices, can be used. Here, FSEs were generated using de-epidermalized dermis (DED) and collagen matrices MatriDerm^® and Mucomaix^®. Our aim was to validate the MatriDerm- and Mucomaix-based FSEs for the use as in vitro models of wound healing. Therefore, we first characterized the FSEs in terms of skin development and cell proliferation. Proper dermal and epidermal morphogenesis was established in all FSEs and was comparable to ex vivo human skin models. Extension of culture time improved the organization of the epidermal layers and the basement membrane in MatriDerm-based FSE but resulted in rapid degradation of the Mucomaix-based FSE. After applying a standardized burn injury to the models, re-epithelization occurred in the DED- and MatriDerm-based FSEs at 2 weeks after injury, similar to ex vivo human skin. High levels of pro-inflammatory cytokines were present in the culture media of all models, but no significant differences were observed between models. We anticipate that these animal-free in vitro models can facilitate research on skin regeneration and can be used to test therapeutic interventions in a preclinical setting to improve wound healing. Full article

(This article belongs to the Special Issue Functional Biomaterials and Skin Wound Healing)

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16 pages, 14250 KiB

Open AccessEditor’s ChoiceArticle

Sequential Release of Panax Notoginseng Saponins and Osteopractic Total Flavone from Poly (_L-Lactic Acid) Scaffold for Treating Glucocorticoid-Associated Osteonecrosis of Femoral Head

by Guiyu Feng, Pingxin Zhang, Jian Huang, Yao Yu, Fenghe Yang, Xueqian Zhao, Wei Wang, Dongyang Li, Song Sun, Xufeng Niu, Limin Chai and Jinyu Li

J. Funct. Biomater. 2023, 14(1), 31; https://doi.org/10.3390/jfb14010031 - 4 Jan 2023

Cited by 5 | Viewed by 2125

Abstract

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (_L-lactic acid) (PLLA) is commonly used in the [...] Read more.

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (_L-lactic acid) (PLLA) is commonly used in the bone tissue engineering field. Panax notoginseng saponins (PNS) and osteopractic total flavone (OTF) promote angiogenesis and osteogenesis, respectively. We designed a sequentially releasing PLLA scaffold including PLLA loaded with OTF (inner layer) and PLLA loaded with PNS (outer layer). We assessed the osteogenic effect of angiogenesis in this scaffold by comparing it with the one-layered scaffold (PLLA embedded with OTF and PNS) in vivo. Results from the micro-CT showed that the data of bone mineral density (BMD), bone volume (BV), and percent bone volume (BV/TV) in the PO-PP group were significantly higher than those in the POP group (p < 0.01). Histological analyses show that the PO-PP scaffold exhibits better angiogenic and osteogenic effects compared with the one-layered scaffold. These might result from the different structures between them, where the sequential release of a bi-layer scaffold achieves the osteogenic effect of vascularization by initially releasing PNS in the outer layer. We further explored the possible mechanism by an immunohistochemistry analysis and an immunofluorescence assay. The results showed that the protein expressions of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1(CD31) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.01); the protein expressions of osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.05). Upregulating the expressions of angiogenic and osteogenic proteins might be the possible mechanism. Full article

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29 pages, 2378 KiB

Open AccessEditor’s ChoiceReview

Updated Perspectives on Direct Vascular Cellular Reprogramming and Their Potential Applications in Tissue Engineered Vascular Grafts

by Saneth Gavishka Sellahewa, Jojo Yijiao Li and Qingzhong Xiao

J. Funct. Biomater. 2023, 14(1), 21; https://doi.org/10.3390/jfb14010021 - 30 Dec 2022

Cited by 6 | Viewed by 3198

Abstract

Cardiovascular disease is a globally prevalent disease with far-reaching medical and socio-economic consequences. Although improvements in treatment pathways and revascularisation therapies have slowed disease progression, contemporary management fails to modulate the underlying atherosclerotic process and sustainably replace damaged arterial tissue. Direct cellular reprogramming [...] Read more.

Cardiovascular disease is a globally prevalent disease with far-reaching medical and socio-economic consequences. Although improvements in treatment pathways and revascularisation therapies have slowed disease progression, contemporary management fails to modulate the underlying atherosclerotic process and sustainably replace damaged arterial tissue. Direct cellular reprogramming is a rapidly evolving and innovative tissue regenerative approach that holds promise to restore functional vasculature and restore blood perfusion. The approach utilises cell plasticity to directly convert somatic cells to another cell fate without a pluripotent stage. In this narrative literature review, we comprehensively analyse and compare direct reprogramming protocols to generate endothelial cells, vascular smooth muscle cells and vascular progenitors. Specifically, we carefully examine the reprogramming factors, their molecular mechanisms, conversion efficacies and therapeutic benefits for each induced vascular cell. Attention is given to the application of these novel approaches with tissue engineered vascular grafts as a therapeutic and disease-modelling platform for cardiovascular diseases. We conclude with a discussion on the ethics of direct reprogramming, its current challenges, and future perspectives. Full article

(This article belongs to the Special Issue Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices)

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27 pages, 2979 KiB

Open AccessEditor’s ChoiceReview

Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review

by Yingkun Hu, Jinghuan Huang, Chunying Chen, Yi Wang, Zhuowen Hao, Tianhong Chen, Junwu Wang and Jingfeng Li

J. Funct. Biomater. 2023, 14(1), 18; https://doi.org/10.3390/jfb14010018 - 29 Dec 2022

Cited by 19 | Viewed by 6266

Abstract

Bone homeostasis (a healthy bone mass) is regulated by maintaining a delicate balance between bone resorption and bone formation. The regulation of physiological bone remodeling by a complex system that involves multiple cells in the skeleton is closely related to bone homeostasis. Loss [...] Read more.

Bone homeostasis (a healthy bone mass) is regulated by maintaining a delicate balance between bone resorption and bone formation. The regulation of physiological bone remodeling by a complex system that involves multiple cells in the skeleton is closely related to bone homeostasis. Loss of bone mass or repair of bone is always accompanied by changes in bone homeostasis. However, due to the complexity of bone homeostasis, we are currently unable to identify all the mechanisms that affect bone homeostasis. To date, bone macrophages have been considered a third cellular component in addition to osteogenic spectrum cells and osteoclasts. As confirmed by co-culture models or in vivo experiments, polarized or unpolarized macrophages interact with multiple components within the bone to ensure bone homeostasis. Different macrophage phenotypes are prone to resorption and formation of bone differently. This review comprehensively summarizes the mechanisms by which macrophages regulate bone homeostasis and concludes that macrophages can control bone homeostasis from osteoclasts, mesenchymal cells, osteoblasts, osteocytes, and the blood/vasculature system. The elaboration of these mechanisms in this narrative review facilitates the development of macrophage-based strategies for the treatment of bone metabolic diseases and bone defects. Full article

(This article belongs to the Special Issue Biomaterials Applications in Bone and Wound Repair)

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23 pages, 5590 KiB

Open AccessEditor’s ChoiceArticle

Antibacterial Electrodeposited Copper-Doped Calcium Phosphate Coatings for Dental Implants

by Camille Pierre, Ghislaine Bertrand, Iltaf Pavy, Olivier Benhamou, Christian Rey, Christine Roques and Christèle Combes

J. Funct. Biomater. 2023, 14(1), 20; https://doi.org/10.3390/jfb14010020 - 29 Dec 2022

Cited by 10 | Viewed by 3754

Abstract

Dental implants provide a good solution for the replacement of tooth roots. However, the full restoration of tooth functions relies on the bone-healing period before positioning the abutment and the crown on the implant, with the associated risk of post-operative infection. This study [...] Read more.

Dental implants provide a good solution for the replacement of tooth roots. However, the full restoration of tooth functions relies on the bone-healing period before positioning the abutment and the crown on the implant, with the associated risk of post-operative infection. This study aimed at developing a homogeneous and adherent thin calcium phosphate antibacterial coating on titanium dental implants by electrodeposition to favor both implant osseointegration and to limit peri-implantitis. By combining global (XRD, FTIR-ATR, elemental titration) and local (SEM, Raman spectroscopy on the coating surface and thickness) characterization techniques, we determined the effect of electrodeposition time on the characteristics and phases content of the coating and the associated mechanism of its formation. The 1-min-electrodeposited CaP coating (thickness: 2 ± 1 μm) was mainly composed of nano-needles of octacalcium phosphate. We demonstrated its mechanical stability after screwing and unscrewing the dental implant in an artificial jawbone. Then, we showed that we can reach a high copper incorporation rate (up to a 27% Cu/(Cu+Ca) molar ratio) in this CaP coating by using an ionic exchange post-treatment with copper nitrate solution at different concentrations. The biological properties (antibiofilm activity and cytotoxicity) were tested in vitro using a model of mixed bacteria biofilm mimicking peri-implantitis and the EN 10993-5 standard (direct contact), respectively. An efficient copper-doping dose was determined, providing an antibiofilm property to the coating without cytotoxic side effects. By combining the electrodeposition and copper ionic exchange processes, we can develop an antibiofilm calcium phosphate coating on dental implants with a tunable thickness and phases content. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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13 pages, 1935 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of the Cytotoxicity of Cationic Polymers on Glioblastoma Cancer Stem Cells

by Conor McCartin, Juliette Blumberger, Candice Dussouillez, Patricia Fernandez de Larrinoa, Monique Dontenwill, Christel Herold-Mende, Philippe Lavalle, Béatrice Heurtault, Stéphane Bellemin-Laponnaz, Sylvie Fournel and Antoine Kichler

J. Funct. Biomater. 2023, 14(1), 17; https://doi.org/10.3390/jfb14010017 - 28 Dec 2022

Cited by 6 | Viewed by 3327

Abstract

Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug [...] Read more.

Cationic polymers such as polyethylenimine (PEI) have found a pervasive place in laboratories across the world as gene delivery agents. However, their applications are not limited to this role, having found a place as delivery agents for drugs, in complexes known as polymer-drug conjugates (PDCs). Yet a potentially underexplored domain of research is in their inherent potential as anti-cancer therapeutic agents, which has been indicated by several studies. Even more interesting is the recent observation that certain polycations may present a significantly greater toxicity towards the clinically important cancer stem cell (CSC) niche than towards more differentiated bulk tumour cells. These cells, which possess the stem-like characteristics of self-renewal and differentiation, are highly implicated in cancer drug resistance, tumour recurrence and poor clinical prognosis. The search for compounds which may target and eliminate these cells is thus of great research interest. As such, the observation in our previous study on a PEI-based PDC which showed a considerably higher toxicity of PEI towards glioblastoma CSCs (GSCs) than on more differentiated glioma (U87) cells led us to investigate other cationic polymers for a similar effect. The evaluation of the toxicity of a range of different types of polycations, and an investigation into the potential source of GSC’s sensitivity to such compounds is thus described. Full article

(This article belongs to the Special Issue Functionalized Polymeric Biomaterials: Design and Applications)

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15 pages, 1981 KiB

Open AccessEditor’s ChoiceArticle

Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge

by Andrey Romanyuk, Ruixue Wang, Alexander Marin, Benjamin M. Janus, Eric I. Felner, Dengning Xia, Yenny Goez-Gazi, Kendra J. Alfson, Abdul S. Yunus, Eric A. Toth, Gilad Ofek, Ricardo Carrion, Jr., Mark R. Prausnitz, Thomas R. Fuerst and Alexander K. Andrianov

J. Funct. Biomater. 2023, 14(1), 16; https://doi.org/10.3390/jfb14010016 - 27 Dec 2022

Cited by 11 | Viewed by 4290

Abstract

Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in [...] Read more.

Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease. Full article

(This article belongs to the Special Issue Synthetic Polymers for the Delivery of Vaccines and Therapeutics)

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21 pages, 5096 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Degradation and Photoactivated Antibacterial Activity of a Hemin-CaP Microsphere-Loaded Coating on Pure Magnesium

by Lixin Long, Yang Song, Xiaoyi Tian, Lanyue Cui, Chengbao Liu, Shuoqi Li, Yu Wang and Rongchang Zeng

J. Funct. Biomater. 2023, 14(1), 15; https://doi.org/10.3390/jfb14010015 - 26 Dec 2022

Cited by 4 | Viewed by 3229

Abstract

Photoactivated sterilization has received more attention in dealing with implant-associated infections due to its advantages of rapid and effective bacteriostasis and broad-spectrum antibacterial activity. Herein, a micro-arc oxidation (MAO)/polymethyltrimethoxysilane (PMTMS)@hemin-induced calcium-bearing phosphate microsphere (Hemin-CaP) coating was prepared on pure magnesium (Mg) via MAO [...] Read more.

Photoactivated sterilization has received more attention in dealing with implant-associated infections due to its advantages of rapid and effective bacteriostasis and broad-spectrum antibacterial activity. Herein, a micro-arc oxidation (MAO)/polymethyltrimethoxysilane (PMTMS)@hemin-induced calcium-bearing phosphate microsphere (Hemin-CaP) coating was prepared on pure magnesium (Mg) via MAO processing and dipping treatments. The morphology and composition of the coating were characterized via scanning electron microscopy, Fourier transform infrared spectrometer, X-ray diffractometer and X-ray photoelectron spectrometer. Corrosion behavior was evaluated through electrochemical and hydrogen evolution tests. The release of Fe³⁺ ions at different immersion times was measured with an atomic absorption spectrophotometer. Antibacterial performance and cytotoxicity were assessed using the spread plate method, MTT assay and live/dead staining experiment. The results showed that the corrosion current density of the MAO/PMTMS@(Hemin-CaP) coating (4.41 × 10⁻⁸ A·cm⁻²) was decreased by two orders of magnitude compared to that of pure Mg (3.12 × 10⁻⁶ A·cm⁻²). Photoactivated antibacterial efficiencies of the Hemin-CaP microspheres and MAO/PMTMS@(Hemin-CaP) coating reached about 99% and 92%, respectively, which we attributed to the photothermal and photodynamic properties of hemin with a porphyrin ring. Moreover, based on the release of Fe³⁺ ions, the MC3T3-E1 pre-osteoblasts’ viability reached up to 125% after a 72 h culture, indicating a positive effect of the coating in promoting cell growth. Thus, this novel composite coating holds a promising application as bone implants. Full article

(This article belongs to the Special Issue Corrosion Science in Biodegradable Implants)

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27 pages, 4268 KiB

Open AccessEditor’s ChoiceReview

Polyethyleneimine-Based Drug Delivery Systems for Cancer Theranostics

by Chong Zhao and Benqing Zhou

J. Funct. Biomater. 2023, 14(1), 12; https://doi.org/10.3390/jfb14010012 - 23 Dec 2022

Cited by 33 | Viewed by 7386

Abstract

With the development of nanotechnology, various types of polymer-based drug delivery systems have been designed for biomedical applications. Polymer-based drug delivery systems with desirable biocompatibility can be efficiently delivered to tumor sites with passive or targeted effects and combined with other therapeutic and [...] Read more.

With the development of nanotechnology, various types of polymer-based drug delivery systems have been designed for biomedical applications. Polymer-based drug delivery systems with desirable biocompatibility can be efficiently delivered to tumor sites with passive or targeted effects and combined with other therapeutic and imaging agents for cancer theranostics. As an effective vehicle for drug and gene delivery, polyethyleneimine (PEI) has been extensively studied due to its rich surface amines and excellent water solubility. In this work, we summarize the surface modifications of PEI to enhance biocompatibility and functionalization. Additionally, the synthesis of PEI-based nanoparticles is discussed. We further review the applications of PEI-based drug delivery systems in cancer treatment, cancer imaging, and cancer theranostics. Finally, we thoroughly consider the outlook and challenges relating to PEI-based drug delivery systems. Full article

(This article belongs to the Special Issue Hydrogels for Biointerface Application)

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14 pages, 2127 KiB

Open AccessEditor’s ChoiceArticle

Mechanical Properties and Biocompatibility of 3D Printing Acrylic Material with Bioactive Components

by Zbigniew Raszewski, Katarzyna Chojnacka, Julita Kulbacka and Marcin Mikulewicz

J. Funct. Biomater. 2023, 14(1), 13; https://doi.org/10.3390/jfb14010013 - 23 Dec 2022

Cited by 14 | Viewed by 3715

Abstract

The aim of this study was to create a 3D printing material with bioactive properties that potentially could be used for a transparent removable orthodontic appliance. Materials and methods. To acrylic monomers, four bioactive glasses at 10% concentration were added, which release Ca, [...] Read more.

The aim of this study was to create a 3D printing material with bioactive properties that potentially could be used for a transparent removable orthodontic appliance. Materials and methods. To acrylic monomers, four bioactive glasses at 10% concentration were added, which release Ca, P, Si and F ions. The materials were printed on a 3D printer and tested for flexural strength (24 h and 30 days), sorption and solubility (7 days), ion release to artificial saliva pH = 4 and 7 (42 days) and cytotoxicity in the human fibroblast model. The released ions were determined by plasma spectrometry (Ca, P and Si ions) and ion-selective electrode (F measurement)s. Results: The material obtained released Ca²⁺ and PO₄³⁻ ions for a period of 42 days when using glass Biomin C at pH 4. The flexural strength depended on the direction in which the sample was printed relative to the 3D printer platform. Vertically printed samples had a resistance greater than 20%. The 10% Biomin C samples post-cured for 30 min with light had a survival rate of the cells after 72 h of 85%.Conclusions. Material for 3D printing with bioactive glass in its composition, which releases ions, can be used in the production of orthodontic aligners. Full article

(This article belongs to the Special Issue Advanced Materials and Technologies in Orthodontics)

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15 pages, 3118 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Polydopamine-Coated Alginate Microgels: Process Optimization and In Vitro Validation

by Iriczalli Cruz-Maya, Simona Zuppolini, Mauro Zarrelli, Elisabetta Mazzotta, Anna Borriello, Cosimino Malitesta and Vincenzo Guarino

J. Funct. Biomater. 2023, 14(1), 2; https://doi.org/10.3390/jfb14010002 - 20 Dec 2022

Cited by 5 | Viewed by 3189

Abstract

In the last decade, alginate-based microgels have gained relevant interest as three-dimensional analogues of extracellular matrix, being able to support cell growth and functions. In this study, core-shell microgels were fabricated by self-polymerization of dopamine (DA) molecules under mild oxidation and in situ [...] Read more.

In the last decade, alginate-based microgels have gained relevant interest as three-dimensional analogues of extracellular matrix, being able to support cell growth and functions. In this study, core-shell microgels were fabricated by self-polymerization of dopamine (DA) molecules under mild oxidation and in situ precipitation of polydopamine (PDA) onto alginate microbeads, processed by electro fluid dynamic atomization. Morphological (optical, SEM) and chemical analyses (ATR-FTIR, XPS) confirmed the presence of PDA macromolecules, distributed onto the microgel surface. Nanoindentation tests also indicated that the PDA coating can influence the biomechanical properties of the microgel surfaces—i.e., σmaxALG = 0.45 mN vs. σmaxALG@PDA = 0.30 mN—thus improving the interface with hMSCs as confirmed by in vitro tests; in particular, protein adsorption and viability tests show a significant increase in adhesion and cell proliferation, strictly related to the presence of PDA. Hence, we concluded that PDA coating contributes to the formation of a friendly interface able to efficiently support cells’ activities. In this perspective, core-shell microgels may be suggested as a novel symmetric 3D model to study in vitro cell interactions. Full article

(This article belongs to the Special Issue State-of-the-Art Functional Biomaterials in Italy)

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16 pages, 3802 KiB

Open AccessEditor’s ChoiceArticle

Degradable Pure Magnesium Used as a Barrier Film for Oral Bone Regeneration

by Xianfeng Shan, Yu Xu, Sharafadeen Kunle Kolawole, Ling Wen, Zhenwei Qi, Weiwei Xu and Junxiu Chen

J. Funct. Biomater. 2022, 13(4), 298; https://doi.org/10.3390/jfb13040298 - 15 Dec 2022

Cited by 17 | Viewed by 2618

Abstract

The barrier membrane plays an extremely critical role in guided bone regeneration (GBR), which determines the success or failure of GBR technology. In order to obtain barrier membranes with high mechanical strength and degradability, some researchers have focused on degradable magnesium alloys. However, [...] Read more.

The barrier membrane plays an extremely critical role in guided bone regeneration (GBR), which determines the success or failure of GBR technology. In order to obtain barrier membranes with high mechanical strength and degradability, some researchers have focused on degradable magnesium alloys. However, the degradation rate of pure Mg-based materials in body fluids is rather fast, thus posing an urgent problem to be solved in oral clinics. In this study, a novel micro-arc oxidation (MAO) surface-treated pure Mg membrane was prepared. Electrochemical tests, immersion experiments and in vivo experiments were carried out to investigate its potential use as a barrier membrane. The experimental results showed that the corrosion resistance of a pure Mg membrane treated by MAO is better than that of the uncoated pure Mg. The results of cell experiments showed no obvious cytotoxicity, which suggests the enhanced differentiation of osteoblasts. At the same time, the MAO-Mg membrane showed better biological activity than the pure Ti membrane in the early stage of implantation, exhibiting relatively good bone regeneration ability. Consequently, the MAO membrane has been proven to possess good application prospects for guided bone regeneration. Full article

(This article belongs to the Special Issue Advanced Biodegradable Biomaterials)

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16 pages, 3482 KiB

Open AccessEditor’s ChoiceArticle

Corrosion Behavior and Biocompatibility of Hot-Extruded Mg–Zn–Ga–(Y) Biodegradable Alloys

by Viacheslav Bazhenov, Anna Li, Artem Iliasov, Vasily Bautin, Sofia Plegunova, Andrey Koltygin, Alexander Komissarov, Maxim Abakumov, Nikolay Redko and Kwang Seon Shin

J. Funct. Biomater. 2022, 13(4), 294; https://doi.org/10.3390/jfb13040294 - 12 Dec 2022

Cited by 11 | Viewed by 2579

Abstract

Fixation screws and other temporary magnesium alloy fixation devices are used in orthopedic practice because of their biodegradability, biocompatibility and acceptable biodegradation rates. The substitution of dissolving implant by tissues during the healing process is one of the main requirements for biodegradable implants. [...] Read more.

Fixation screws and other temporary magnesium alloy fixation devices are used in orthopedic practice because of their biodegradability, biocompatibility and acceptable biodegradation rates. The substitution of dissolving implant by tissues during the healing process is one of the main requirements for biodegradable implants. Previously, clinical tests showed the effectiveness of Ga ions on bone tissue regeneration. This work is the first systematic study on the corrosion rate and biocompatibility of Mg–Zn–Ga–(Y) alloys prepared by hot extrusion, where Ga is an additional major alloying element, efficient as a bone-resorption inhibitor. Most investigated alloys have a low corrosion rate in Hanks’ solution close to ~0.2 mm/year. No cytotoxic effects of Mg–2Zn–2Ga (wt.%) alloy on MG63 cells were observed. Thus, considering the high corrosion resistance and good biocompatibility, the Mg–2Zn–2Ga alloy is possible for applications in osteosynthesis implants with improved bone tissue regeneration ability. Full article

(This article belongs to the Special Issue Metallic Biomaterials for Medical Applications)

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12 pages, 1962 KiB

Open AccessEditor’s ChoiceArticle

Differential Foreign Body Reactions between Branched and Linear Glucomannan Scaffolds

by Yuwei Li, Yu Liu, Senio Campos de Souza, Tzuwei Chao, Lei Dong, Guoxing Sun, Chunming Wang and Yiming Niu

J. Funct. Biomater. 2022, 13(4), 293; https://doi.org/10.3390/jfb13040293 - 11 Dec 2022

Cited by 2 | Viewed by 2159

Abstract

The extent and patterns of foreign body reaction (FBR) influence the function and feasibility of biomaterials. Polysaccharides, as an important biomaterial category, have received increasing attention in diverse biomaterials design and biomedical applications due to their excellent polymeric and biocompatible characteristics. Their biological [...] Read more.

The extent and patterns of foreign body reaction (FBR) influence the function and feasibility of biomaterials. Polysaccharides, as an important biomaterial category, have received increasing attention in diverse biomaterials design and biomedical applications due to their excellent polymeric and biocompatible characteristics. Their biological effects are usually associated with their monosaccharide composition or functional groups, yet the contribution of their glycan structure is still unknown. Herein, two glucomannans, similar in composition and molecular weight with differences in glycan structure, linear-chain (Konjac glucomannan, KGM), and branched-chain (Bletilla striata polysaccharide, BSP), were adopted to explore the host–biomaterials interaction. After acetyl modification, these polysaccharides were fabricated into electrospun scaffolds to reduce the impacts derived from the physical properties and surface morphology. According to a systematic study of their biological effects on immune cells and host response in a subcutaneous implantation model in vivo, it was revealed that acetyl KGM (acKGM) scaffolds caused a stronger FBR than acetyl BSP materials. Additionally, acKGM could stimulate macrophages to release pro-inflammatory cytokines, suggesting the influence of sugar chain arrangement on FBR and providing clues for the fine regulation of immune response and novel biomaterials design. Full article

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22 pages, 15639 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Surface Modification of Additively Fabricated Titanium-Based Implants by Means of Bioactive Micro-Arc Oxidation Coatings for Bone Replacement

by Anna I. Kozelskaya, Sven Rutkowski, Johannes Frueh, Aleksey S. Gogolev, Sergei G. Chistyakov, Sergey V. Gnedenkov, Sergey L. Sinebryukhov, Andreas Frueh, Vladimir S. Egorkin, Evgeny L. Choynzonov, Mikhail Buldakov, Denis E. Kulbakin, Evgeny N. Bolbasov, Anton P. Gryaznov, Ksenia N. Verzunova, Margarita D. Apostolova and Sergei I. Tverdokhlebov

J. Funct. Biomater. 2022, 13(4), 285; https://doi.org/10.3390/jfb13040285 - 8 Dec 2022

Cited by 30 | Viewed by 3852

Abstract

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them—oxide, another two—calcium phosphates) were obtained, [...] Read more.

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them—oxide, another two—calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings. Full article

(This article belongs to the Special Issue Biomaterials for Drug Release and Tissue Engineering)

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13 pages, 2786 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Biomechanical Testing of Two-Unit Bridges and a Comparison of Replacement Retention Depending on a Cementation Medium, Replacement Position, and Gap Size

by Alena Findrik Balogová, Viktória Rajťúková, Ľuboš Chromý, Andrej Somoš, Gabriela Ižaríková and Radovan Hudák

J. Funct. Biomater. 2022, 13(4), 286; https://doi.org/10.3390/jfb13040286 - 8 Dec 2022

Cited by 1 | Viewed by 1750

Abstract

Dental replacements are placed between the abutment teeth. The exceptions are two-unit bridges, as they are supported by a single tooth prepared only on one side of the missing tooth. The presented study deals with an analysis of a pressure force action on [...] Read more.

Dental replacements are placed between the abutment teeth. The exceptions are two-unit bridges, as they are supported by a single tooth prepared only on one side of the missing tooth. The presented study deals with an analysis of a pressure force action on two-unit bridges placed in the frontal part (20 samples), where the pressure action is lower, and in the distal part (20 samples), where the pressure action is higher. A CAD program by 3Shape was used for digital designing with two different gap settings, 10 μm (20 samples) and 30 μm (20 samples). Two-unit bridges were attached to the prepared tooth using two types of dental cement (20/20 samples), which were selected for their physical and bioactive properties. All two-unit bridges (a total of 80 samples) were fabricated from CoCr alloys on Mlab cusing R by applying the Selective Laser Melting (SLM) technology. Mechanical testing was performed using the Inspekt5 table blue. The obtained data were used to verify the hypotheses—a difference between both types of cement (A ≠ B), a difference between the frontal and distal two-unit bridges (F ≠ D) and a difference between the gap sizes (10 ≠ 30). To confirm the given theories, data were statistically evaluated using the F-test and subsequent t-tests. The resulting p-value was compared with the level of significance (α = 0.05). A statistical evaluation revealed a significant difference between the compared groups; however, no explicit correlation between the individual groups of specimens was identified. Full article

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15 pages, 3339 KiB

Open AccessEditor’s ChoiceArticle

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens

by Zi-Jian Chen, Jia-Cheng Lv, Zhi-Guo Wang, Fei-Yu Wang, Ren-Huan Huang, Zi-Li Zheng, Jia-Zhuang Xu and Jing Wang

J. Funct. Biomater. 2022, 13(4), 280; https://doi.org/10.3390/jfb13040280 - 7 Dec 2022

Cited by 12 | Viewed by 2690

Abstract

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine [...] Read more.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria. Full article

(This article belongs to the Section Dental Biomaterials)

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47 pages, 3376 KiB

Open AccessEditor’s ChoiceReview

Metal Oxide Nanoparticles: Review of Synthesis, Characterization and Biological Effects

by Andreea Mariana Negrescu, Manuela S. Killian, Swathi N. V. Raghu, Patrik Schmuki, Anca Mazare and Anisoara Cimpean

J. Funct. Biomater. 2022, 13(4), 274; https://doi.org/10.3390/jfb13040274 - 5 Dec 2022

Cited by 103 | Viewed by 18384

Abstract

In the last few years, the progress made in the field of nanotechnology has allowed researchers to develop and synthesize nanosized materials with unique physicochemical characteristics, suitable for various biomedical applications. Amongst these nanomaterials, metal oxide nanoparticles (MONPs) have gained increasing interest due [...] Read more.

In the last few years, the progress made in the field of nanotechnology has allowed researchers to develop and synthesize nanosized materials with unique physicochemical characteristics, suitable for various biomedical applications. Amongst these nanomaterials, metal oxide nanoparticles (MONPs) have gained increasing interest due to their excellent properties, which to a great extent differ from their bulk counterpart. However, despite such positive advantages, a substantial body of literature reports on their cytotoxic effects, which are directly correlated to the nanoparticles’ physicochemical properties, therefore, better control over the synthetic parameters will not only lead to favorable surface characteristics but may also increase biocompatibility and consequently lower cytotoxicity. Taking into consideration the enormous biomedical potential of MONPs, the present review will discuss the most recent developments in this field referring mainly to synthesis methods, physical and chemical characterization and biological effects, including the pro-regenerative and antitumor potentials as well as antibacterial activity. Moreover, the last section of the review will tackle the pressing issue of the toxic effects of MONPs on various tissues/organs and cell lines. Full article

(This article belongs to the Special Issue Women in Science: Functional Biomaterials)

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25 pages, 5435 KiB

Open AccessEditor’s ChoiceArticle

Adsorption and Release Properties of Drug Delivery System Naproxen-SBA-15: Effect of Surface Polarity, Sodium/Acid Drug Form and pH

by Ľuboš Zauška, Eva Beňová, Martina Urbanová, Jiří Brus, Vladimír Zeleňák, Virginie Hornebecq and Miroslav Almáši

J. Funct. Biomater. 2022, 13(4), 275; https://doi.org/10.3390/jfb13040275 - 5 Dec 2022

Cited by 30 | Viewed by 3162

Abstract

Mesoporous silica SBA-15 was prepared via sol-gel synthesis and functionalized with different types of organosilanes containing various organic functional groups: (3-aminopropyl)triethoxysilane (SBA-15-NH₂), (3-mercaptopropyl)triethoxysilane (SBA-15-SH), triethoxymethylsilane (SBA-15-CH₃), triethoxyphenylsilane (SBA-15-Ph), and (3-isocynatopropyl)triethoxysilane (SBA-15-NCO). The prepared materials were investigated as drug delivery [...] Read more.

Mesoporous silica SBA-15 was prepared via sol-gel synthesis and functionalized with different types of organosilanes containing various organic functional groups: (3-aminopropyl)triethoxysilane (SBA-15-NH₂), (3-mercaptopropyl)triethoxysilane (SBA-15-SH), triethoxymethylsilane (SBA-15-CH₃), triethoxyphenylsilane (SBA-15-Ph), and (3-isocynatopropyl)triethoxysilane (SBA-15-NCO). The prepared materials were investigated as drug delivery systems for naproxen. As model drugs, naproxen acid (HNAP) and its sodium salt (NaNAP) were used. Mentioned medicaments belong to the group of non-steroidal anti-inflammatory drugs (NSAIDs). The prepared materials were characterized by different analytical methods such as transmission electron microscopy (TEM), infrared spectroscopy (IR), nitrogen adsorption/desorption analysis (N₂), thermogravimetric analysis (TG), ¹H, ¹³C and ²³Na solid-state nuclear magnetic resonance spectroscopy (¹H, ¹³C and ²³Na ss-NMR). The abovementioned analytical techniques confirmed the successful grafting of functional groups to the SBA-15 surface and the adsorption of drugs after the impregnation process. The BET area values decreased from 927 m² g⁻¹ for SBA-15 to 408 m² g⁻¹ for SBA-15-NCO. After drug encapsulation, a more significant decrease in surface area was observed due to the filling of pores with drug molecules, while the most significant decrease was observed for the SBA-15-NH₂ material (115 m² g⁻¹ for NaNAP and 101 m² g⁻¹ for HNAP). By combining TG and nitrogen adsorption results, the occurrence of functional groups and the affinity of drugs to the carriers’ surface were calculated. The dominant factor was the volume of functional groups and intermolecular interactions. The highest drug affinity values were observed for phenyl and amine-modified materials (SBA-15-Ph = 1.379 μmol m⁻² mmol⁻¹ for NaNAP, 1.761 μmol m⁻² mmol⁻¹ for HNAP and SBA-15-NH₂ = 1.343 μmol m⁻² mmol⁻¹ for NaNAP, 1.302 μmol m⁻² mmol⁻¹ for HNAP) due to the formation of hydrogen bonds and π-π interactions, respectively. Drug release properties and kinetic studies were performed at t = 37 °C (normal human body temperature) in different media with pH = 2 as simulated human gastric fluid and pH = 7.4, which simulated a physiological environment. Determination of drug release quantity was performed with UV-VIS spectroscopy. The surface polarity, pH and naproxen form influenced the total released amount of drug. In general, naproxen sodium salt has a higher solubility than its acid form, thus significantly affecting drug release from surface-modified SBA-15 materials. Different pH conditions involved surface protonation and formation/disruption of intermolecular interactions, influencing both the release rate and the total released amount of naproxen. Different kinetic models, zero-order, first-order, Higuchi and Hixson–Crowell models, were used to fit the drug release data. According to the obtained experimental results, the drug release rates and mechanisms were determined. Full article

(This article belongs to the Special Issue Biomedical Applications of Mixed-Charge Nanomaterials)

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17 pages, 3976 KiB

Open AccessEditor’s ChoiceArticle

Healing Patterns of Non-Collagenated Bovine and Collagenated Porcine Xenografts Used for Sinus Floor Elevation: A Histological Study in Rabbits

by Yuhei Miyauchi, Takayuki Izutani, Yuki Teranishi, Takahisa Iida, Yasushi Nakajima, Samuel Porfirio Xavier and Shunsuke Baba

J. Funct. Biomater. 2022, 13(4), 276; https://doi.org/10.3390/jfb13040276 - 5 Dec 2022

Cited by 8 | Viewed by 2002

Abstract

Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 [...] Read more.

Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 weeks. The loss of dimensions of the elevated area and the percentages of new bone, xenograft remnants, osteoclastic zones, vessels, inflammatory infiltrates, and soft tissues were analyzed. Three regions were evaluated: close to the bone walls (bone wall region), subjacent the sinus mucosa (submucosa region), and the center of the elevated area (middle region). The primary variables were the percentage of new bone and xenograft remnants. Results: Between 2 and 8 weeks, the elevated areas showed a reduction of 16.3% and 52.2% in the DBBM and collagenated groups, respectively (p < 0.01 between the two areas after 8 weeks). After 8 weeks, the highest content of new bone was observed in the bone wall region, which was higher in the collagenated group than in the DBBM group (41.6% and 28.6%, respectively; p < 0.01). A similar quantity of new bone was found between the two groups in other regions. A higher percentage of vessels in all regions evaluated (p < 0.01) and soft tissue in the sub-mucosa region (p < 0.05) was found in the collagenated group than in the DBBM group. Conclusions: The present study showed that both xenografts allowed new bone formation. In comparison with the non-collagenated xenograft, the collagenated xenograft underwent higher resorption, resulting in greater shrinkage of the elevated space after sinus lifting and a higher content of new bone in the regions close to the bone walls. Clinical relevance: In this study, the region adjacent to the bone wall showed the highest new bone content. This region resembles the base of the sinus, closest to the sinus floor and walls, and is the most important region from a clinical point of view because it is where the implant will be installed. Residues of the biomaterial remained after 8 weeks of healing. Other reports have shown that these biomaterial residues may interfere with the integration of implants. Full article

(This article belongs to the Special Issue Bone Regeneration and Repair Materials)

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15 pages, 3929 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of an Injectable Biphasic Calcium Sulfate/Hydroxyapatite Cement for the Augmentation of Fenestrated Pedicle Screws in Osteoporotic Vertebrae: A Biomechanical Cadaver Study

by Xinggui Tian, Deepak B. Raina, Corina Vater, David Kilian, Tilman Ahlfeld, Ivan Platzek, Ute Nimtschke, Magnus Tägil, Lars Lidgren, Alexander Thomas, Uwe Platz, Klaus-Dieter Schaser, Alexander C. Disch and Stefan Zwingenberger

J. Funct. Biomater. 2022, 13(4), 269; https://doi.org/10.3390/jfb13040269 - 1 Dec 2022

Cited by 7 | Viewed by 3252

Abstract

Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an [...] Read more.

Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an injectable, bioactive, and degradable calcium sulfate/hydroxyapatite (CaS/HA) cement could increase the maximum pull-out force of pedicle screws in osteoporotic vertebrae. Herein, 17 osteoporotic thoracic and lumbar vertebrae were obtained from a single fresh-frozen human cadaver and instrumented with fenestrated pedicle screws. The right screw in each vertebra was augmented with CaS/HA cement and the un-augmented left side served as a paired control. The cement distribution, interdigitation ability, and cement leakage were evaluated using radiographs. Furthermore, pull-out testing was used to evaluate the immediate mechanical effect of CaS/HA augmentation on the pedicle screws. The CaS/HA cement presented good distribution and interdigitation ability without leakage into the spinal canal. Augmentation significantly enhanced the maximum pull-out force of the pedicle screw in which the augmented side was 39.0% higher than the pedicle-screw-alone side. Therefore, the novel biodegradable biphasic CaS/HA cement could be a promising material for pedicle screw augmentation in the osteoporotic spine. Full article

(This article belongs to the Special Issue Active Biomedical Materials and Their Applications)

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22 pages, 12629 KiB

Open AccessEditor’s ChoiceArticle

TiO₂/HA and Titanate/HA Double-Layer Coatings on Ti6Al4V Surface and Their Influence on In Vitro Cell Growth and Osteogenic Potential

by Michalina Ehlert, Aleksandra Radtke, Natalia Forbot, Tomasz Jędrzejewski, Katarzyna Roszek, Patrycja Golińska, Grzegorz Trykowski and Piotr Piszczek

J. Funct. Biomater. 2022, 13(4), 271; https://doi.org/10.3390/jfb13040271 - 1 Dec 2022

Cited by 6 | Viewed by 2794

Abstract

Hydroxyapatite (HA) layers are appropriate biomaterials for use in the modification of the surface of implants produced inter alia from a Ti6Al4V alloy. The issue that must be solved is to provide implants with appropriate biointegration properties, enabling the permanent link between them [...] Read more.

Hydroxyapatite (HA) layers are appropriate biomaterials for use in the modification of the surface of implants produced inter alia from a Ti6Al4V alloy. The issue that must be solved is to provide implants with appropriate biointegration properties, enabling the permanent link between them and bone tissues, which is not so easy with the HA layer. Our proposition is the use of the intermediate layer ((IL) = TiO₂, and titanate layers) to successfully link the HA coating to a metal substrate (Ti6Al4V). The morphology, structure, and chemical composition of Ti6Al4V/IL/HA systems were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectrometry (EDS). We evaluated the apatite-forming ability on the surface of the layer in simulated body fluid. We investigated the effects of the obtained systems on the viability and growth of human MG-63 osteoblast-like cells, mouse L929 fibroblasts, and adipose-derived human mesenchymal stem cells (ADSCs) in vitro, as well as on their osteogenic properties. Based on the obtained results, we can conclude that both investigated systems reflect the physiological environment of bone tissue and create a biocompatible surface supporting cell growth. However, the nanoporous TiO₂ intermediate layer with osteogenesis-supportive activity seems most promising for the practical application of Ti6Al4V/TiO₂/HA as a system of bone tissue regeneration. Full article

(This article belongs to the Special Issue Biocompatibility of Functional Biomaterials)

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23 pages, 3177 KiB

Open AccessEditor’s ChoiceReview

Performance of PEO/Polymer Coatings on the Biodegradability, Antibacterial Effect and Biocompatibility of Mg-Based Materials

by Arash Fattah-alhosseini, Razieh Chaharmahali, Armin Rajabi, Kazem Babaei and Mosab Kaseem

J. Funct. Biomater. 2022, 13(4), 267; https://doi.org/10.3390/jfb13040267 - 30 Nov 2022

Cited by 44 | Viewed by 4106

Abstract

Magnesium (Mg) alloys have recently attracted attention in biomedicine as biodegradable materials with non-toxic degradable products. Such compounds have become a frontier in the study of biodegradable materials because of their remarkable biomechanical compatibility and superior biocompatibility. The use of Mg-based implants reduces [...] Read more.

Magnesium (Mg) alloys have recently attracted attention in biomedicine as biodegradable materials with non-toxic degradable products. Such compounds have become a frontier in the study of biodegradable materials because of their remarkable biomechanical compatibility and superior biocompatibility. The use of Mg-based implants reduces the negative consequences of permanent biological implants by eliminating the necessity for biomaterial surgery following the healing process. However, the quick deterioration, formation of considerable gas of hydrogen volumes and a rise in the body environment pH are obstacles in the application of Mg as an implant material. Hence, compelling advances for erosion resistance and biocompatibility of magnesium and its alloys are noteworthy. Surface modification may be a practical approach because it improves the erosion resistance compared with extensive preparation of a treated surface for progressed bone recovery and cell attachment. Coating produced by plasma electrolytic oxidation (PEO) seems a compelling method in order to enhance magnesium and the properties of its alloys. PEO-formed coatings cannot provide long-term protection in the physiological environment due to their porous nature. Thus, a polymer coating is applied on the porous PEO-formed coating, which is steadily applied on the surface. Polymer coatings improve the biocompatibility properties of Mg and its alloys and increase corrosion resistance. In this article, the most recent advancements in PEO/polymer composite coatings are reviewed, and the biocompatibility of such coatings is examined. Full article

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14 pages, 3511 KiB

Open AccessEditor’s ChoiceArticle

Formulation and Process Optimization of Rauvolfia serpentina Nanosuspension by HPMC and In Vitro Evaluation of ACE Inhibitory Potential

by Syeeda Iram Touqeer, Nazish Jahan, Naseem Abbas and Ahsan Ali

J. Funct. Biomater. 2022, 13(4), 268; https://doi.org/10.3390/jfb13040268 - 30 Nov 2022

Cited by 12 | Viewed by 3843

Abstract

Angiotensin converting enzyme (ACE) overactivation is one of the primary causes of hypertension, which leads to cardiovascular disorders all over the world. In the scientific world, nanosuspension is a novel area of study that could offer an alternative treatment for active pharmaceuticals that [...] Read more.

Angiotensin converting enzyme (ACE) overactivation is one of the primary causes of hypertension, which leads to cardiovascular disorders all over the world. In the scientific world, nanosuspension is a novel area of study that could offer an alternative treatment for active pharmaceuticals that are not well soluble in water. Since active compounds’ bioavailability is reduced by their poor solubility, there are eventually fewer applications. Drug solubility, dissolving rate, and bioavailability are improved by nanosuspension, which shrinks medication particle size into the nanoscale range and boosts the surface area to volume ratio of the drug. There is a need to prepare Rauvolfia serpentina’s nanosuspension in order to get around some of the major challenges that it faces because of its poor solubility and wide range of biological activities. Using the antisolvent precipitation approach, a nanosuspension of Rauvolfia serpentina was created with hydroxy propyl methyl cellulose (HPMC). Rouvolfia serpentina nanosuspensions were prepared using a design of expert (DOE) approach, which allowed for the evaluation of key process parameters. To get an optimal sample, the effects of stabilizer concentration and anti-solvent volume on particle size, zeta potential, and PdI using CCD-RSM were investigated. Using the substrate Hippuryl-histidyl-leucine, the in vitro ACE inhibitory potential was assessed. On human erythrocytes, the safety of nanosuspension was evaluated in vitro. The ideal value of independent variables was discovered to be 0.25% w/v in order to achieve the desired response. Using scanning electron microscopy, the morphology of optimized nanosuspension was discovered to be rod-shaped (SEM). Compared to nanoformulation, crude extract had higher ACE inhibitory potential (83.11%). Human erythrocytes were found to be unaffected by nano-sized particles. Full article

(This article belongs to the Special Issue Biocompatibility of Functional Biomaterials)

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13 pages, 2471 KiB

Open AccessEditor’s ChoiceArticle

Positive Effects of UV-Photofunctionalization of Titanium Oxide Surfaces on the Survival and Differentiation of Osteogenic Precursor Cells—An In Vitro Study

by Marco Roy, Alessandro Corti, Barbara Dorocka-Bobkowska and Alfonso Pompella

J. Funct. Biomater. 2022, 13(4), 265; https://doi.org/10.3390/jfb13040265 - 25 Nov 2022

Cited by 8 | Viewed by 2337

Abstract

Introduction: The UVC-irradiation (“UV-photofunctionalization”) of titanium dental implants has proved to be capable of removing carbon contamination and restoring the ability of titanium surfaces to attract cells involved in the process of osteointegration, thus significantly enhancing the biocompatibility of implants and favoring the [...] Read more.

Introduction: The UVC-irradiation (“UV-photofunctionalization”) of titanium dental implants has proved to be capable of removing carbon contamination and restoring the ability of titanium surfaces to attract cells involved in the process of osteointegration, thus significantly enhancing the biocompatibility of implants and favoring the post-operative healing process. To what extent the effect of UVC irradiation is dependent on the type or the topography of titanium used, is still not sufficiently established. Objective: The present study was aimed at analyzing the effects of UV-photofunctionalization on the TiO₂ topography, as well as on the gene expression patterns and the biological activity of osteogenic cells, i.e., osteogenic precursors cultured in vitro in the presence of different titanium specimens. Methodology: The analysis of the surface roughness was performed by atomic force microscopy (AFM) on machined surface grade 2, and sand-blasted/acid-etched surface grades 2 and 4 titanium specimens. The expression of the genes related with the process of healing and osteogenesis was studied in the MC3T3-E1 pre-osteoblastic murine cells, as well as in MSC murine stem cells, before and after exposure to differently treated TiO₂ surfaces. Results: The AFM determinations showed that the surface topographies of titanium after the sand-blasting and acid-etching procedures, look very similar, independently of the grade of titanium. The UVC-irradiation of the TiO₂ surface was found to induce an increase in the cell survival, attachment and proliferation, which was positively correlated with an increased expression of the osteogenesis-related genes Runx2 and alkaline phosphatase (ALP). Conclusion: Overall, our findings expand and further support the current view that UV-photofunctionalization can indeed restore biocompatibility and osteointegration of TiO₂ implants, and suggest that this at least in part occurs through a stimulation of the osteogenic differentiation of the precursor cells. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Biotechnology: Applications in Dental Medicine)

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