Journal of Functional Biomaterials

3D-printed titanium (Ti) cages present an attractive alternative for addressing issues related to osteoporosis-induced fractures, accidental fractures, and spinal fusion surgery due to disc herniation. These Ti-based bone implants possess superior strength compared to other metals, allowing for versatile applications in orthopedic scenarios. However, when used as standalone solutions, certain considerations may arise, such as interaction with soft tissues. Therefore, to overcome these issues, the combination with hydrogel has been considered. In this study, to impart Ti with regenerative abilities a 3D-printed Ti cage was loaded with gelatin and hyaluronic acid (G-H) to improve the cell attachment ability of the Ti-based bone implants. The void spaces within the mesh structure of the 3D Ti cage were filled with G-H, creating a network of micro-sized pores. The filled G-H acted as the bridge for the cells to migrate toward the large inner pores of the 3D Ti cage. Due to the microporous surface and slow release of gelatin and hyaluronic acid, the biocompatibility of the coated Ti cage was increased with an elevation in osteoconduction as depicted by the up-regulation of bone-related gene expressions. The in vivo implantation in the rabbit femur model showed enhanced bone regeneration due to the coated G-H on the Ti cage compared to the pristine hollow Ti cage. The G-H filled the large holes of the 3D Ti cage that acted as a bridge for the cells to travel inside the implant and aided in the fast regeneration of bone. Full article

Ossiculoplasty is a surgical operation performed to restore auditory transmission through the reconstruction of the ossicular chain using prosthetics. Tissue bioengineering has assumed a pivotal role in implementing alternatives to conventional ossicular middle ear replacement prostheses, to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore, for the first time in current literature, the feasibility of a biohybrid middle ear prosthesis, composed of titanium surrounded by a bone extracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using an immunofluorescence assay to analyze osteoblasts’ gene expression profiles (Alp, Runx2, Col1a1, Osx, and Bglap), and we counted the presence of collagen as a marker of hASC’s ability to secrete an extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of an extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium’s ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, in order to obtain a biohybrid device. Our experience seems encouraging; thus, we advocate for further in vivo research to corroborate our results regarding bone transplantation. Full article

The current study reports the use of silver (Ag) and samarium (Sm) as dopants to improve the properties of standard bioglass in terms of biological performance. This experiment considers thin films of doped bioglass obtained by pulsed laser deposition (PLD) and spin coating (SC). For both methods, some parameters were gradually varied, as the main objective was to produce a bioglass that could be used in biomedical fields. In order to study the morphology, the phase composition and other properties, the samples obtained were subjected to multiple analyses, such as thermal analysis, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FT-IR), Raman spectroscopy, and x-ray diffraction (XRD). Furthermore, the in vitro bioactivity of the samples, as assessed through simulated body fluid (SBF) immersion, as well as immunocytochemistry and evaluation of actin filaments, assessed through fluorescence microscopy, are reported. The results confirmed the formation of the designed vitreous target employed as the source of material in the PLD experiments only at sintering temperatures below 800 °C; this vitreous nature was preserved in the grown film as well. The presence of Ag and Ce dopants in the parent glassy matrix was validated for all stages, from powder, to target, to PLD/SC-derived coatings. Additionally, it was demonstrated that the surface topography of the layers can be adjusted by using substrates with different roughness or by modulating the processing parameters, such as substrate temperature and working pressure in PLD, rotation speed, and number of layers in SC. The developed material was found to be highly bioactive after 28 days of immersion in SBF, but it was also found to be a potential candidate for inhibiting the growth of Gram-negative bacteria and a suitable support for cell growth and proliferation. Full article

The unique physical properties of heavy ion beams, particularly their distinctive depth–dose distribution and sharp lateral dose reduction profiles, have led to their widespread adoption in tumor therapy worldwide. However, the physical properties of heavy ion beams must be investigated to deliver a sufficient dose to tumors without damaging organs at risk. These studies should be performed on phantoms made of biomaterials that closely mimic human tissue. Polymers can serve as soft tissue substitutes and are suitable materials for building radiological phantoms due to their physical, mechanical, biological, and chemical properties. Extensive research, development, and applications of polymeric biomaterials have been encouraged due to these properties. In this study, we investigated the ionization, recoils, phonon release, collision events, and lateral straggle properties of polymeric biomaterials that closely resemble soft tissue using lithium-ion beams and Monte Carlo Transport of Ions in Matter simulation. The results indicated that the Bragg peak position closest to soft tissue was achieved with a 7.3% difference in polymethylmethacrylate, with an average recoils value of 10.5%. Additionally, average values of 33% were observed in collision events and 22.6% in lateral straggle. A significant contribution of this study to the existing literature lies in the exploration of secondary interactions alongside the assessment of linear energy transfer induced by the ⁷Li beam used for treatment. Furthermore, we analyzed the tissue-equivalent properties of polymer biomaterials using heavy ion beams, taking into account phonon release resulting from ionization, recoils, lateral straggle, and all other interactions. This approach allows for the evaluation of the most suitable polymeric biomaterials for heavy ion therapy while considering the full range of interactions involved. Full article

The synthesis of graphene-based materials for drug delivery represents an area of active research, and the use of graphene in drug delivery systems is promising due to its unique properties. Thus, in the present work, we discuss the potential of few-layer graphene in a hydrogel system for dopamine release. The hydrogels are frequently used for these systems for their special physico-chemical properties, which can ensure that the drug is effectively released in time. However, the release from such structures is mostly determined by diffusion alone, and to overcome this restriction, the hydrogel can be “improved” with nanoscale fillers like graphene. The release kinetics of the composite obtained were analyzed to better understand how the use of graphene, instead of the more common graphene oxide (GO) and reduced graphene oxide (rGO), affects the characteristics of the system. Thus, the systems developed in this study consist of three main components: biopolymer, graphene, and dopamine. The hydrogels with graphene were prepared by combining two different solutions, one with polyacrylic acid and agarose and one with graphene prepared by the exfoliation method with microwave irradiation. The drug delivery systems were developed by adding dopamine to the obtained hydrogels. After 24 h of release, the presence of dopamine was observed, demonstrating that the system developed can slow down the drug’s degradation because of the interactions with the graphene nanoplates and the polymer matrix. Full article

The porous structure can reduce the elastic modulus of a dental implant and better approximate the elastic characteristics of the material to the alveolar bone. Therefore, it has the potential to alleviate bone stress shielding around the implant. However, natural bone is heterogeneous, and, thus, introducing a porous structure may produce pathological bone stress. Herein, we designed a porous implant with axial gradient variation in porosity to alleviate stress shielding in the cancellous bone while controlling the peak stress value in the cortical bone margin region. The biomechanical distribution characteristics of axial gradient porous implants were studied using a finite element method. The analysis showed that a porous implant with an axial gradient variation in porosity ranging from 55% to 75% was the best structure. Under vertical and oblique loads, the proportion of the area with a stress value within the optimal stress interval at the bone–implant interface (BII) was 40.34% and 34.57%, respectively, which was 99% and 65% higher compared with that of the non-porous implant in the control group. Moreover, the maximum equivalent stress value in the implant with this pore parameter was 64.4 MPa, which was less than 1/7 of its theoretical yield strength. Axial gradient porous implants meet the strength requirements for bone implant applications. They can alleviate stress shielding in cancellous bone without increasing the stress concentration in the cortical bone margin, thereby optimizing the stress distribution pattern at the BII. Full article

Male survivors of childhood cancer have been known to be afflicted with azoospermia. To combat this, the isolation and purification of spermatogonial stem cells (SSCs) are crucial. Implementing scaffolds that emulate the extracellular matrix environment is vital for promoting the regeneration and proliferation of SSCs. This research aimed to evaluate the efficiency of nanocomposite scaffolds based on alginate, chitosan, and graphene oxide (GO) in facilitating SSCs proliferation. To analyze the cytotoxicity of the scaffolds, an MTT assay was conducted at 1, 3, and 7 days, and the sample containing 30 µg/mL of GO (ALGCS/GO30) exhibited the most favorable results, indicating its optimal performance. The identity of the cells was confirmed using flow cytometry with C-Kit and GFRα1 markers. The scaffolds were subjected to various analyses to characterize their properties. FTIR was employed to assess the chemical structure, XRD to examine crystallinity, and SEM to visualize the morphology of the scaffolds. To evaluate the proliferation of SSCs, qRT-PCR was used. The study’s results demonstrated that the ALGCS/GO30 nanocomposite scaffold exhibited biocompatibility and facilitated the attachment and proliferation of SSCs. Notably, the scaffold displayed a significant increase in proliferation markers compared to the control group, indicating its ability to support SSC growth. The expression level of the PLZF protein was assessed using the Immunocytochemistry method. The observations confirmed the qRT-PCR results, which indicated that the nanocomposite scaffolds had higher levels of PLZF protein expression than scaffolds without GO. The biocompatible ALGCS/GO30 is a promising alternative for promoting SSC proliferation in in vitro applications. Full article

Bone critical-size defects and non-union fractures have no intrinsic capacity for self-healing. In this context, the emergence of bone engineering has allowed the development of functional alternatives. The aim of this study was to evaluate the capacity of ASC spheroids in bone regeneration using a synergic strategy with 3D-printed scaffolds made from poly (lactic acid) (PLA) and nanostructured hydroxyapatite doped with carbonate ions (CHA) in a rat model of cranial critical-size defect. In summary, a set of results suggests that ASC spheroidal constructs promoted bone regeneration. In vitro results showed that ASC spheroids were able to spread and interact with the 3D-printed scaffold, synthesizing crucial growth factors and cytokines for bone regeneration, such as VEGF. Histological results after 3 and 6 months of implantation showed the formation of new bone tissue in the PLA/CHA scaffolds that were seeded with ASC spheroids. In conclusion, the presence of ASC spheroids in the PLA/CHA 3D-printed scaffolds seems to successfully promote bone formation, which can be crucial for a significant clinical improvement in critical bone defect regeneration. Full article

Bacterial infections are a common mode of failure for medical implants. This study aims to develop antibacterial polyelectrolyte multilayer (PEM) coatings that contain a plant-derived condensed tannin polymer (Tanfloc, TAN) with inherent antimicrobial activity. Tanfloc is amphoteric, and herein we show that it can be used as either a polyanion or a polycation in PEMs, thereby expanding the possibility of its use in PEM coatings. PEMs are ordinarily formed using a polycation and a polyanion, in which the functional (ionic) groups of the two polymers are complexed to each other. However, using the amphoteric polymer Tanfloc with weakly basic amine and weakly acidic catechol and pyrogallol groups enables PEM formation using only one or the other of its functional groups, leaving the other functional group available to impart antibacterial activity. This work demonstrates Tanfloc-containing PEMs using multiple counter-polyelectrolytes including three polyanionic glycosaminoglycans of varying charge density, and the polycations N,N,N-trimethyl chitosan and polyethyleneimine. The layer-by-layer (LbL) assembly of PEMs was monitored using in situ Fourier-transform surface plasmon resonance (FT-SPR), confirming a stable LbL assembly. X-ray photoelectron spectroscopy (XPS) was used to evaluate surface chemistry, and atomic force microscopy (AFM) was used to determine the surface roughness. The LDH release levels from cells cultured on the Tanfloc-containing PEMs were not statistically different from those on the negative control (p > 0.05), confirming their non-cytotoxicity, while exhibiting remarkable antiadhesive and bactericidal properties against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus), respectively. The antibacterial effects were attributed to electrostatic interactions and Tanfloc’s polyphenolic nature. This work underscores the potential of Tanfloc as a versatile biomaterial for combating infections on surfaces. Full article

The intricate microenvironment at the wound site, coupled with the multi-phase nature of the healing process, pose significant challenges to the development of wound repair treatments. In recent years, applying the distinctive benefits of hydrogels to the development of wound repair strategies has yielded some promising results. Multifunctional hydrogels, by meeting the different requirements of wound healing stages, have greatly improved the healing effectiveness of chronic wounds, offering immense potential in wound repair applications. This review summarized the recent research and applications of multifunctional hydrogels in wound repair. The focus was placed on the research progress of diverse multifunctional hydrogels, and their mechanisms of action at different stages of wound repair were discussed in detail. Through a comprehensive analysis, we found that multifunctional hydrogels play an indispensable role in the process of wound repair by providing a moist environment, controlling inflammation, promoting angiogenesis, and effectively preventing infection. However, further implementation of multifunctional hydrogel-based therapeutic strategies also faces various challenges, such as the contradiction between the complexity of multifunctionality and the simplicity required for clinical translation and application. In the future, we should work to address these challenges, further optimize the design and preparation of multifunctional hydrogels, enhance their effectiveness in wound repair, and promote their widespread application in clinical practice. Full article

Silicon nitride is a bioceramic with great potential, and multiple studies have demonstrated its biocompatibility and antibacterial properties. In this study, silicon nitride was prepared by a microwave sintering technique that was different from common production methods. SEM and pore distribution analysis revealed the microstructure of microwave-sintered silicon nitride with obvious pores. Mechanical performance analysis shows that microwave sintering can improve the mechanical properties of silicon nitride. The CCK-8 method was used to demonstrate that microwave-sintered silicon nitride has no cytotoxicity and good cytocompatibility. From SEM and CLSM observations, it was observed that there was good adhesion and cross-linking of cells during microwave-sintered silicon nitride, and the morphology of the cytoskeleton was good. Microwave-sintered silicon nitride has been proven to be non-cytotoxic. In addition, the antibacterial ability of microwave-sintered silicon nitride against Staphylococcus aureus and Escherichia coli was tested, proving that it has a good antibacterial ability similar to the silicon nitride prepared by commonly used processes. Compared with silicon nitride prepared by gas pressure sintering technology, microwave-sintered silicon nitride has excellent performance in mechanical properties, cell compatibility, and antibacterial properties. This indicates its enormous potential as a substitute material for manufacturing bone implants. Full article

Previous research has reported on hidden damage within the dentin introduced by cryopreservation, but the effect on the mechanical properties of the hard tissues at tooth level remains unclear. The main objective of this study is to investigate the effect of cryopreservation on the mechanical properties of teeth. A matched sample of 234 premolars of 117 children (9 ≤ age ≤ 16 years), bilaterally extracted for orthodontic reasons, were included. For each child, one tooth was randomly allocated to the cryopreservation group and the contralateral tooth was assigned to the control group. Static compression tests were performed to determine load to failure, stiffness, and toughness. In a subgroup of 20 teeth, a cyclic preloading or chewing simulation was performed. Additionally, the fracture mode was determined, and the microstructure of the fractured surfaces was examined using a scanning electron microscope (SEM). Linear mixed model analyses could not detect a statistical difference in the mean load to failure (p = 0.549), mean toughness (p = 0.968), or mean stiffness (p = 0.150) between cryopreserved and non-cryopreserved teeth. No significant difference in load to failure after cyclic preloading was detected between groups (p = 0.734). SEM analysis revealed comparable fracture characteristics between groups. It is concluded that cryopreservation does not affect the mean load to failure, stiffness, or toughness of teeth, indicating that hidden damage in the dentin is not critical at tooth level. Full article

This laboratory experiment was conducted with the objective of augmenting the mechanical properties of glass ionomer cement (GIC) via altering the composition of GIC luting powder through the introduction of micron-sized silanized glass fibres (GFs). Experimental GICs were prepared through the addition of two concentrations of GFs (0.5% and 1.0% by weight) to the powder of commercially available GIC luting materials. The effect of GF in set GIC was internally evaluated using micro-CT while the mechanical attributes such as nano hardness (nH), elastic modulus (EM), compressive strength (CS), and diametral tensile strength (DTS) were gauged. Additionally, the physical properties such as water solubility and sorption, contact angle (CA), and film thickness were evaluated. Reinforced Ketac Cem Radiopaque (KCR) GIC with 0.5 wt.% GF achieved improved nH, EM, CS, and DTS without affecting the film thickness, CA or internal porosity of the set GIC cement. In contrast, both GF-GIC formulations of Medicem (MC) GIC showed the detrimental effect of the GF incorporation. Reinforcing KCR GIC with 0.5 wt.% silanized GFs could improve the physical and mechanical attributes of luting material. Silanized GF, with optimal concentration within the GIC powder, can be used as a functional additive in KCR GIC with promising results. Full article

In this study, we have developed innovative polymer nanocomposites by integrating magnesium-aluminum layered double hydroxide (LDH)-based nanocarriers modified with functional molecules into a fully biobased poly(lactic acid)/poly(butylene succinate-co-adipate) (PLA/PBSA) matrix. These LDH-based hybrid host-guest systems contain bioactive compounds like rosmarinic acid, ferulic acid, and glycyrrhetinic acid, known for their antioxidant, antimicrobial, and anti-inflammatory properties. The bioactive molecules can be gradually released from the nanocarriers over time, allowing for sustained and controlled delivery in various applications, such as active packaging or cosmetics. The morphological analysis of the polymer composites, prepared using a discontinuous mechanical mixer, revealed the presence of macroaggregates and nano-lamellae at the polymer interface. This resulted in an enhanced water vapor permeability compared to the original blend. Furthermore, the migration kinetics of active molecules from the thin films confirmed a controlled release mechanism based on their immobilization within the lamellar system. Scaling-up experiments evaluated the materials’ morphology and mechanical and thermal properties. Remarkably, stretching deformation and a higher shear rate during the mixing process enhanced the dispersion and distribution of the nanocarriers, as confirmed by the favorable mechanical properties of the materials. Full article

Ulcerative colitis (UC) is a refractory chronic inflammatory disease involving the colon and rectum, falling under the category of inflammatory bowel disease (IBD). The accumulation of reactive oxygen species (ROS) in local tissues has been identified as a crucial contributor to the escalation of inflammatory responses. Therefore, eliminating ROS in the inflamed colon is a promising approach to treating UC. Nanomaterials with intrinsic enzyme-like activities (nanozymes) have shown significant therapeutic potential in UC. In this study, we found that platinum nanoparticles (Pt NPs) exhibited remarkable superoxide dismutase (SOD) and catalase (CAT) cascade catalytic activities, as well as effective hydroxyl radical (•OH) scavenging ability. The in vitro experiments showed that Pt NPs could eliminate excessive ROS to protect cells against oxidative stress. In the colitis model, oral administration of Pt NPs (loaded in chitosan/alginate hydrogel) could significantly alleviate UC, including reducing the colon length, the damaged epithelium, and the infiltration of inflammatory cells. Without appreciable systemic toxicity, Pt NPs represent a novel therapeutic approach to UC and are expected to achieve long-term inflammatory remission. Full article

Current research on the fatigue properties of degradable zinc alloy stents has not yet considered the issue of the fatigue life changing with material properties during the dynamic degradation process. Therefore, in this paper, we established a fatigue damage algorithm to study the fatigue problem affected by the changing of material properties during the dynamic degradation process of the stent under the action of pulsating cyclic loading. Three models: the dynamic degradation model, the dynamic degradation model under pulsating cyclic loading, and the coupled model of fatigue damage and dynamic degradation, were developed to verify the effect of fatigue damage on stent life. The results show that fatigue damage leads to a deeper degree of inhomogeneous degradation of the stent, which affects the service life of the stent. Fatigue damage is a factor that cannot be ignored. Therefore, when studying the mechanical properties and lifetime of degradable stents, incorporating fatigue damage into the study can help more accurately assess the lifetime of the stents. Full article

Multidrug resistance (MDR) is a key factor in chemotherapy failure and tumor recurrence. The inhibition of drug efflux and autophagy play important roles in MDR therapy. Herein, a multifunctional delivery system (HA-MIL-125@DVMA) was prepared for synergistically reverse tumor MDR. Tumor-targeted hollow MIL-125-Ti nanoparticles were used to load the doxorubicin–vitamin E succinate (DV) prodrug and 3-methyladenine (3-MA) to enhance reverse MDR effects. The pH-sensitive DV can kill tumor cells and inhibit P-gp-mediated drug efflux, and 3-MA can inhibit autophagy. HA-MIL-125@DVMA had uniformly distributed particle size and high drug-load content. The nanoparticles could effectively release the drugs into tumor microenvironment due to the rapid hydrazone bond-breaking under low pH conditions, resulting in a high cumulative release rate. In in vitro cellular experiments, the accumulation of HA-MIL-125@DVMA and HA-MIL-125@DV in MCF-7/ADR cells was significantly higher than that in the control groups. Moreover, the nanoparticles significantly inhibited drug efflux in the cells, ensuring the accumulation of the drugs in cell cytoplasm and causing drug-resistant cells’ death. Importantly, HA-MIL-125@DVMA effectively inhibited tumor growth without changes in body weight in tumor-bearing mice. In summary, the combination of the acid-sensitive prodrug DV and autophagy inhibitor 3-MA in a HA-MIL-125 nanocarrier can enhance the antitumor effect and reverse tumor MDR. Full article

Periodontitis is a destructive inflammatory disease characterized by microbial infection that damages the tissues supporting the tooth (alveolar bone, gingiva, periodontal ligament, and cementum), ultimately resulting in the loss of teeth. The ultimate goal of periodontal therapy is to achieve the regeneration of all of the periodontal tissues. Thus, tissue engineering approaches have been evolving from simple membranes or grafts to more complex constructs. Hydrogels are highly hydrophilic polymeric networks with the ability to simulate the natural microenvironment of cells. In particular, hydrogels offer several advantages when compared to other forms of scaffolds, such as tissue mimicry and sustained drug delivery. Moreover, hydrogels can maintain a moist environment similar to the oral cavity. Hydrogels allow for precise placement and retention of regenerative materials at the defect site, minimizing the potential for off-target effects and ensuring that the treatment is focused on the specific defect site. As a mechanism of action, the sustained release of drugs presented by hydrogels allows for control of the disease by reducing the inflammation and attracting host cells to the defect site. Several therapeutic agents, such as antibiotics, anti-inflammatory and osteogenic drugs, have been loaded into hydrogels, presenting effective benefits in periodontal health and allowing for sustained drug release. This review discusses the causes and consequences of periodontal disease, as well as the advantages and limitations of current treatments applied in clinics. The main components of hydrogels for periodontal regeneration are discussed focusing on their different characteristics, outcomes, and strategies for drug delivery. Novel methods for the fabrication of hydrogels are highlighted, and clinical studies regarding the periodontal applications of hydrogels are reviewed. Finally, limitations in current research are discussed, and potential future directions are proposed. Full article

Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct, called a stent, inside arteries to restore blood flow. However, due to lack of patient-specific design, the commercial products cannot be used with different vessel anatomies. In this review, we have summarized the drawbacks in existing commercial metal stents which face problems of restenosis and inflammatory responses, owing to the development of neointimal hyperplasia. Further, we have highlighted the fabrication of stents using biodegradable polymers, which can circumvent most of the existing limitations. In this regard, we elaborated on the utilization of new fabrication methodologies based on additive manufacturing such as three-dimensional printing to design patient-specific stents. Finally, we have discussed the functionalization of these stent surfaces with suitable bioactive molecules which can prove to enhance their properties in preventing thrombosis and better healing of injured blood vessel lining. Full article