Biomaterials for Tissue Engineering and Regeneration

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Biomacromolecules, Biobased and Biodegradable Polymers".

Deadline for manuscript submissions: closed (30 December 2022) | Viewed by 58393

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Guest Editor
Faculty of Engineering and Natural Sciences, Tampere University, P. O. Box 589, 33014 Tampere, Finland
Interests: biodegradable polymers; biomaterials; chitosan; hydroxyapatite; scaffolds; ionic substitution; stem cells; tissue engineering and regeneration
Special Issues, Collections and Topics in MDPI journals
Faculty of Science, University of Zagreb, Horvatovac 102a, 10 000 Zagreb, Croatia
Interests: cancer biology; stem cells; drug delivery; scaffolds; tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomaterials serve as an integral component of tissue engineering and their development is crucial for the further progress of new and efficient approaches in the regenerative medicine of bone, cartilage, tendons and ligaments, skin, soft tissue wounds, cardiac muscle, vascular tissues, and neural tissues. Polymer-based biomaterials are extensively studied in the field of tissue engineering due to their biocompatible and biodegradable properties. This Special Issue, entitled Biomaterials for Tissue Engineering and Regeneration, is devoted to recent advances in the development of synthetic and/or natural biomaterial scaffolds, hydrogels, polypeptides, polymer-based composites, and composites based on polymers and inorganic materials such as bioactive ceramics and glasses. New technologies (e.g., bioprinting, additive manufacturing) for forming biomaterials for tissue engineering of three-dimensional (3D) constructs are of great interest.

The scope of this Special Issue includes, but is not limited to, the following topics:

  • 3D polymer-based scaffolds;
  • Structure–property relationships of polymeric and composite biomaterials;
  • In vitro and in vivo biodegradability, biocompatibility, anticancer, and antibacterial properties;
  • Polymers for tissue engineering and regeneration;
  • Stem cell engineering;
  • Drug delivery (e.g., solid lipid nanoparticles, hydrogels);
  • New technologies for scaffold formation (3D fabrication).

Improvements in the field of tissue regeneration relies on bringing together experts from different fields, such as materials science, polymer science, mechanical engineering, biomaterials, cell biology, nanotechnology, immunology, etc. For this Special Issue, we invite scientists from different fields to contribute with recent original research and review articles.

Dr. Antonia Ressler
Dr. Inga Urlic
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biodegradable polymers
  • biomaterials
  • bioprinting
  • drug delivery
  • hydrogels
  • scaffolds
  • stem cells
  • tissue engineering

Published Papers (20 papers)

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20 pages, 5250 KiB  
Article
Physio-Chemical and Biological Characterization of Novel HPC (Hydroxypropylcellulose):HAP (Hydroxyapatite):PLA (Poly Lactic Acid) Electrospun Nanofibers as Implantable Material for Bone Regenerative Application
by S. Mary Stella, T. M. Sridhar, R. Ramprasath, Jolius Gimbun and U. Vijayalakshmi
Polymers 2023, 15(1), 155; https://doi.org/10.3390/polym15010155 - 29 Dec 2022
Cited by 5 | Viewed by 2162
Abstract
The research on extracellular matrix (ECM) is new and developing area that covers cell proliferation and differentiation and ensures improved cell viability for different biomedical applications. Extracellular matrix not only maintains biological functions but also exhibits properties such as tuned or natural material [...] Read more.
The research on extracellular matrix (ECM) is new and developing area that covers cell proliferation and differentiation and ensures improved cell viability for different biomedical applications. Extracellular matrix not only maintains biological functions but also exhibits properties such as tuned or natural material degradation within a given time period, active cell binding and cellular uptake for tissue engineering applications. The principal objective of this study is classified into two categories. The first phase is optimization of various electrospinning parameters with different concentrations of HAP-HPC/PLA(hydroxyapatite-hydroxypropylcellulose/poly lactic acid). The second phase is in vitro biological evaluation of the optimized mat using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay for bone regeneration applications. Conductivity and dielectric constant were optimized for the production of thin fiber and bead free nanofibrous mat. With this optimization, the mechanical strength of all compositions was found to be enhanced, of which the ratio of 70:30 hit a maximum of 9.53 MPa (megapascal). Cytotoxicity analysis was completed for all the compositions on MG63 cell lines for various durations and showed maximum cell viability on 70:30 composition for more than 48 hrs. Hence, this investigation concludes that the optimized nanofibrous mat can be deployed as an ideal material for bone regenerative applications. In vivo study confirms the HAP-HPC-PLA sample shows more cells and bone formation at 8 weeks than 4 weeks. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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14 pages, 3852 KiB  
Article
A Novel Approach for the Manufacturing of Gelatin-Methacryloyl
by David Grijalva Garces, Carsten Philipp Radtke and Jürgen Hubbuch
Polymers 2022, 14(24), 5424; https://doi.org/10.3390/polym14245424 - 11 Dec 2022
Cited by 2 | Viewed by 1742
Abstract
Gelatin and its derivatives contain cell adhesion moieties as well as sites that enable proteolytic degradation, thus allowing cellular proliferation and migration. The processing of gelatin to its derivatives and/or gelatin-containing products is challenged by its gelation below 30 C. In [...] Read more.
Gelatin and its derivatives contain cell adhesion moieties as well as sites that enable proteolytic degradation, thus allowing cellular proliferation and migration. The processing of gelatin to its derivatives and/or gelatin-containing products is challenged by its gelation below 30 C. In this study, a novel strategy was developed for the dissolution and subsequent modification of gelatin to its derivative gelatin-methacryloyl (GelMA). This approach was based on the presence of urea in the buffer media, which enabled the processing at room temperature, i.e., lower than the sol–gel transition point of the gelatin solutions. The degree of functionalization was controlled by the ratio of reactant volume to the gelatin concentration. Hydrogels with tailored mechanical properties were produced by variations of the GelMA concentration and its degree of functionalization. Moreover, the biocompatibility of hydrogels was assessed and compared to hydrogels formulated with GelMA produced by the conventional method. NIH 3T3 fibroblasts were seeded onto hydrogels and the viability showed no difference from the control after a three-day incubation period. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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26 pages, 19785 KiB  
Article
Bone Formation on Murine Cranial Bone by Injectable Cross-Linked Hyaluronic Acid Containing Nano-Hydroxyapatite and Bone Morphogenetic Protein
by Yuki Hachinohe, Masayuki Taira, Miki Hoshi, Wataru Hatakeyama, Tomofumi Sawada and Hisatomo Kondo
Polymers 2022, 14(24), 5368; https://doi.org/10.3390/polym14245368 - 8 Dec 2022
Cited by 3 | Viewed by 1770
Abstract
New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) [...] Read more.
New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) was changed to a gel (x-tHyA) by mixing with a cross-linker. We prepared two sol–gel (SG) material series, that is, x-tHyA + BMP with and without nHAp (SG I) and x-tHyA + nHAp with and without BMP (SG II). SG I materials in the sol stage were injected into the cranial subcutaneous connective tissues of mice, followed by in vivo gelation, while SG II materials gelled in Teflon rings were surgically placed directly on the cranial bones of rats. The animals were sacrificed 8 weeks after implantation, followed by X-ray analysis and histological examination. The results revealed that bone formation occurred at a high rate (>70%), mainly as ectopic bone in the SG I tests in mouse cranial connective tissues, and largely as bone augmentation in rat cranial bones in the SG II experiments when x-tHyA contained both nHAp and BMP. The prepared x-tHyA + nHAp + BMP SG material can be used as an injection-type osteoinductive bone-forming material. Sub-periosteum injection was expected. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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17 pages, 2802 KiB  
Article
Acceleration of Bone Fracture Healing through the Use of Bovine Hydroxyapatite or Calcium Lactate Oral and Implant Bovine Hydroxyapatite–Gelatin on Bone Defect Animal Model
by Aniek Setiya Budiatin, Junaidi Khotib, Samirah Samirah, Chrismawan Ardianto, Maria Apriliani Gani, Bulan Rhea Kaulika Hadinar Putri, Huzaifah Arofik, Rizka Nanda Sadiwa, Indri Lestari, Yusuf Alif Pratama, Erreza Rahadiansyah and Imam Susilo
Polymers 2022, 14(22), 4812; https://doi.org/10.3390/polym14224812 - 9 Nov 2022
Cited by 2 | Viewed by 2824
Abstract
Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA–GEL (bovine hydroxyapatite–gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, [...] Read more.
Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA–GEL (bovine hydroxyapatite–gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA–GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA–GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA–GEL pellet implants. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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24 pages, 3929 KiB  
Article
In Vitro and In Vivo Cell-Interactions with Electrospun Poly (Lactic-Co-Glycolic Acid) (PLGA): Morphological and Immune Response Analysis
by Ana Chor, Christina Maeda Takiya, Marcos Lopes Dias, Raquel Pires Gonçalves, Tatiana Petithory, Jefferson Cypriano, Leonardo Rodrigues de Andrade, Marcos Farina and Karine Anselme
Polymers 2022, 14(20), 4460; https://doi.org/10.3390/polym14204460 - 21 Oct 2022
Cited by 5 | Viewed by 1930
Abstract
Random electrospun three-dimensional fiber membranes mimic the extracellular matrix and the interfibrillar spaces promotes the flow of nutrients for cells. Electrospun PLGA membranes were analyzed in vitro and in vivo after being sterilized with gamma radiation and bioactivated with fibronectin or collagen. Madin-Darby [...] Read more.
Random electrospun three-dimensional fiber membranes mimic the extracellular matrix and the interfibrillar spaces promotes the flow of nutrients for cells. Electrospun PLGA membranes were analyzed in vitro and in vivo after being sterilized with gamma radiation and bioactivated with fibronectin or collagen. Madin-Darby Canine Kidney (MDCK) epithelial cells and primary fibroblast-like cells from hamster’s cheek paunch proliferated over time on these membranes, evidencing their good biocompatibility. Cell-free irradiated PLGA membranes implanted on the back of hamsters resulted in a chronic granulomatous inflammatory response, observed after 7, 15, 30 and 90 days. Morphological analysis of implanted PLGA using light microscopy revealed epithelioid cells, Langhans type of multinucleate giant cells (LCs) and multinucleated giant cells (MNGCs) with internalized biomaterial. Lymphocytes increased along time due to undegraded polymer fragments, inducing the accumulation of cells of the phagocytic lineage, and decreased after 90 days post implantation. Myeloperoxidase+ cells increased after 15 days and decreased after 90 days. LCs, MNGCs and capillaries decreased after 90 days. Analysis of implanted PLGA after 7, 15, 30 and 90 days using transmission electron microscope (TEM) showed cells exhibiting internalized PLGA fragments and filopodia surrounding PLGA fragments. Over time, TEM analysis showed less PLGA fragments surrounded by cells without fibrous tissue formation. Accordingly, MNGC constituted a granulomatous reaction around the polymer, which resolves with time, probably preventing a fibrous capsule formation. Finally, this study confirms the biocompatibility of electrospun PLGA membranes and their potential to accelerate the healing process of oral ulcerations in hamsters’ model in association with autologous cells. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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13 pages, 8482 KiB  
Article
Injectable Cell-Laden Polysaccharide Hydrogels: In Vivo Evaluation of Cartilage Regeneration
by Yao Fu, Sanne K. Both, Jacqueline R. M. Plass, Pieter J. Dijkstra, Bram Zoetebier and Marcel Karperien
Polymers 2022, 14(20), 4292; https://doi.org/10.3390/polym14204292 - 12 Oct 2022
Cited by 2 | Viewed by 1954
Abstract
Previously, 5% w/v hyaluronic acid-tyramine (HA-TA) and dextran-tyramine (Dex-TA) enzymatically cross-linked hybrid hydrogels were demonstrated to provide a mechanically stable environment, maintain cell viability, and promote cartilaginous-specific matrix deposition in vitro. In this study, 5% w/v hybrid hydrogels were [...] Read more.
Previously, 5% w/v hyaluronic acid-tyramine (HA-TA) and dextran-tyramine (Dex-TA) enzymatically cross-linked hybrid hydrogels were demonstrated to provide a mechanically stable environment, maintain cell viability, and promote cartilaginous-specific matrix deposition in vitro. In this study, 5% w/v hybrid hydrogels were combined with human mesenchymal stem cells (hMSCs), bovine chondrocytes (bCHs), or a combination of both in a 4:1 ratio and subcutaneously implanted in the backs of male and female nude rats to assess the performance of cell-laden hydrogels in tissue formation. Subcutaneous implantation of these biomaterials showed signs of integration of the gels within the host tissue. Histological analysis showed residual fibrotic capsules four weeks after implantation. However, enhanced tissue invasion and some giant cell infiltration were observed in the HA-TA/Dex-TA hydrogels laden with either hMSCs or bCHs but not with the co-culture. Moreover, hMSC-bCH co-cultures showed beneficial interaction with the hydrogels, for instance, in enhanced cell proliferation and matrix deposition. In addition, we provide evidence that host gender has an impact on the performance of bCHs encapsulated in HA-TA/Dex-TA hydrogels. This study revealed that hydrogels laden with different types of cells result in distinct host responses. It can be concluded that 5% w/v hydrogels with a higher concentration of Dex-TA (≥50%) laden with bCH-hMSC co-cultures are adequate for injectable applications and in situ cell delivery in cartilage regeneration approaches. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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15 pages, 5908 KiB  
Article
Bone Healing in Rat Segmental Femur Defects with Graphene-PCL-Coated Borate-Based Bioactive Glass Scaffolds
by Ozgur Basal, Ozlem Ozmen and Aylin M. Deliormanlı
Polymers 2022, 14(18), 3898; https://doi.org/10.3390/polym14183898 - 18 Sep 2022
Cited by 3 | Viewed by 1781
Abstract
Bone is a continually regenerating tissue with the ability to heal after fractures, though healing significant damage requires intensive surgical treatment. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared though polymer foam replication and coated with a graphene-containing poly (ε-caprolactone) (PCL) [...] Read more.
Bone is a continually regenerating tissue with the ability to heal after fractures, though healing significant damage requires intensive surgical treatment. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared though polymer foam replication and coated with a graphene-containing poly (ε-caprolactone) (PCL) layer to support bone repair and regeneration. The effects of graphene concentration (1, 3, 5, 10 wt%) on the healing of rat segmental femur defects were investigated in vivo using male Sprague–Dawley rats. Radiographic imaging, histopathological and immuno-histochemical (bone morphogenetic protein (BMP-2), smooth muscle actin (SMA), and alkaline phosphatase (ALP) examinations were performed 4 and 8 weeks after implantation. Results showed that after 8 weeks, both cartilage and bone formation were observed in all animal groups. Bone growth was significant starting from the 1 wt% graphene-coated bioactive glass-implanted group, and the highest amount of bone formation was seen in the group containing 10 wt% graphene (p < 0.001). Additionally, the presence of graphene nanoplatelets enhanced BMP-2, SMA and ALP levels compared to bare bioactive glass scaffolds. It was concluded that pristine graphene-coated bioactive glass scaffolds improve bone formation in rat femur defects. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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20 pages, 4262 KiB  
Article
Sodium Alginate/Chitosan Scaffolds for Cardiac Tissue Engineering: The Influence of Its Three-Dimensional Material Preparation and the Use of Gold Nanoparticles
by Nohra E. Beltran-Vargas, Eduardo Peña-Mercado, Concepción Sánchez-Gómez, Mario Garcia-Lorenzana, Juan-Carlos Ruiz, Izlia Arroyo-Maya, Sara Huerta-Yepez and José Campos-Terán
Polymers 2022, 14(16), 3233; https://doi.org/10.3390/polym14163233 - 9 Aug 2022
Cited by 12 | Viewed by 3328
Abstract
Natural biopolymer scaffolds and conductive nanomaterials have been widely used in cardiac tissue engineering; however, there are still challenges in the scaffold fabrication, which include enhancing nutrient delivery, biocompatibility and properties that favor the growth, maturation and functionality of the generated tissue for [...] Read more.
Natural biopolymer scaffolds and conductive nanomaterials have been widely used in cardiac tissue engineering; however, there are still challenges in the scaffold fabrication, which include enhancing nutrient delivery, biocompatibility and properties that favor the growth, maturation and functionality of the generated tissue for therapeutic application. In the present work, different scaffolds prepared with sodium alginate and chitosan (alginate/chitosan) were fabricated with and without the addition of metal nanoparticles and how their fabrication affects cardiomyocyte growth was evaluated. The scaffolds (hydrogels) were dried by freeze drying using calcium gluconate as a crosslinking agent, and two types of metal nanoparticles were incorporated, gold (AuNp) and gold plus sodium alginate (AuNp+Alg). A physicochemical characterization of the scaffolds was carried out by swelling, degradation, permeability and infrared spectroscopy studies. The results show that the scaffolds obtained were highly porous (>90%) and hydrophilic, with swelling percentages of around 3000% and permeability of the order of 1 × 10−8 m2. In addition, the scaffolds proposed favored adhesion and spheroid formation, with cardiac markers expression such as tropomyosin, troponin I and cardiac myosin. The incorporation of AuNp+Alg increased cardiac protein expression and cell proliferation, thus demonstrating their potential use in cardiac tissue engineering. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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14 pages, 6034 KiB  
Article
Impact of Three Different Processing Techniques on the Strength and Structure of Juvenile Ovine Pulmonary Homografts
by Johannes J van den Heever, Christiaan J Jordaan, Angélique Lewies, Jacqueline Goedhals, Dreyer Bester, Lezelle Botes, Pascal M Dohmen and Francis E Smit
Polymers 2022, 14(15), 3036; https://doi.org/10.3390/polym14153036 - 27 Jul 2022
Cited by 1 | Viewed by 1741
Abstract
Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on [...] Read more.
Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on the strength and structure of ovine pulmonary homografts harvested 48 h post-mortem. Cells and cellular remnants were present for the cryopreserved group, while the decellularized groups were acellular. The decellularized group had large interfibrillar spaces in the extracellular matrix with uniform collagen distribution, while the additional fixation led to the collagen network becoming dense and compacted. The collagen of the cryopreserved group was collapsed and appeared disrupted and fractured. There were no significant differences in strength and elasticity between the groups. Compared to cryopreservation, decellularization without fixation can be considered an alternative processing technique to maintain a well-organized collagen matrix and tissue strength of homografts. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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22 pages, 10013 KiB  
Article
Characterization and Evaluation of Composite Biomaterial Bioactive Glass–Polylactic Acid for Bone Tissue Engineering Applications
by Georgina Carbajal-De la Torre, Nancy N. Zurita-Méndez, María de Lourdes Ballesteros-Almanza, Javier Ortiz-Ortiz, Miriam Estévez and Marco A. Espinosa-Medina
Polymers 2022, 14(15), 3034; https://doi.org/10.3390/polym14153034 - 27 Jul 2022
Cited by 6 | Viewed by 2346
Abstract
The limitations associated with the clinical use of autographs and allografts are driving efforts to develop relevant and applicable biomaterial substitutes. In this research, 3D porous scaffolds composed of bioactive glass (BG) obtained through the sol-gel technique and polylactic acid (PLA) synthesized via [...] Read more.
The limitations associated with the clinical use of autographs and allografts are driving efforts to develop relevant and applicable biomaterial substitutes. In this research, 3D porous scaffolds composed of bioactive glass (BG) obtained through the sol-gel technique and polylactic acid (PLA) synthesized via lactic acid (LA) ring-opening polymerization were prepared by the gel-pressing technique. Two different weight compositions were evaluated, namely, BG70-PLA30 and BG30-PLA70. The structure and morphology of the resulting scaffolds were analysed by FTIR, XRD, SEM, and under ASTM F1635 standard characterizations. The results confirmed that BG promotes the formation of a hydroxy-carbonated apatite (HAp) layer on composites when immersed in simulated body fluid (SBF). Biodegradability evaluations were carried out according to the ISO 10993-13:2010 standard. In addition, electrochemical evaluations were performed in both Hank’s and SBF solutions at 37 °C in order to analyse the degradation of the material. This evaluation allowed us to observe that both samples showed an activation mechanism in the early stages followed by pseudo-passivation due to physical bioactive glass characteristics, suggesting an improvement in the formation of the HAp nucleation. The described composites showed excellent resistance to degradation and outstanding suitability for bone tissue engineering applications. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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11 pages, 5562 KiB  
Article
In Vitro Tissue Reconstruction Using Decellularized Pericardium Cultured with Cells for Ligament Regeneration
by Mika Suzuki, Tsuyoshi Kimura, Yukina Yoshida, Mako Kobayashi, Yoshihide Hashimoto, Hironobu Takahashi, Tatsuya Shimizu, Shota Anzai, Naoko Nakamura and Akio Kishida
Polymers 2022, 14(12), 2351; https://doi.org/10.3390/polym14122351 - 10 Jun 2022
Cited by 5 | Viewed by 2252
Abstract
Recent applications of decellularized tissues have included the ectopic use of their sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are fabricated with the desired functions to employ them to a target tissue. The aim of this study was to develop [...] Read more.
Recent applications of decellularized tissues have included the ectopic use of their sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are fabricated with the desired functions to employ them to a target tissue. The aim of this study was to develop a 3D reconstruction method using a recellularized pericardium to overcome the difficulties in cell infiltration into tight and dense tissues, such as ligament and tendon tissues. Decellularized pericardial tissues were prepared using the high hydrostatic pressurization (HHP) and surfactant methods. The pericardium consisted of bundles of aligned fibers. The bundles were slightly disordered in the surfactant decellularization method compared to the HHP decellularization method. The mechanical properties of the pericardium were maintained after the HHP and surfactant decellularizations. The HHP-decellularized pericardium was rolled up into a cylindrical formation. Its mechanical behavior was similar to that of a porcine anterior cruciate ligament in tensile testing. NIH3T3, C2C12, and mesenchymal stem cells were adhered with elongation and alignment on the HHP- and surfactant-decellularized pericardia, with dependences on the cell type and decellularization method. When the recellularized pericardium was rolled up into a cylinder formation and cultured by hanging circulation for 2 days, the cylinder formation and cellular elongation and alignment were maintained on the decellularized pericardium, resulting in a layer structure of cells in a cross-section. According to these results, the 3D-reconstructed decellularized pericardium with cells has the potential to be an attractive alternative to living tissues, such as ligament and tendon tissues. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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10 pages, 1211 KiB  
Article
In-Vitro Endothelialization Assessment of Heparinized Bovine Pericardial Scaffold for Cardiovascular Application
by My Thi Ngoc Nguyen and Ha Le Bao Tran
Polymers 2022, 14(11), 2156; https://doi.org/10.3390/polym14112156 - 26 May 2022
Cited by 2 | Viewed by 1898
Abstract
(1) Background: Hemocompatibility is a critical challenge for tissue-derived biomaterial when directly contacting the bloodstream. In addition to surface modification with heparin, endothelialization of the grafted material is suggested to improve long-term clinical efficacy. This study aimed to evaluate the ability to endothelialize [...] Read more.
(1) Background: Hemocompatibility is a critical challenge for tissue-derived biomaterial when directly contacting the bloodstream. In addition to surface modification with heparin, endothelialization of the grafted material is suggested to improve long-term clinical efficacy. This study aimed to evaluate the ability to endothelialize in vitro of heparinized bovine pericardial scaffolds. (2) Methods: bovine pericardial scaffolds were fabricated and heparinized using a layer-by-layer assembly technique. The heparinized scaffolds were characterized for heparin content, surface morphology, and blood compatibility. Liquid extraction of the samples was prepared for cytotoxicity testing on human endothelial cells. The in-vitro endothelialization was determined via human endothelial cell attachment and proliferation on the scaffold. (3) Results: The heparinized bovine pericardial scaffold exhibited a heparin coating within its microfiber network. The scaffold surface immobilized with heparin performed good anti-thrombosis and prevented platelet adherence. The proper cytotoxicity impact was observed for a freshly used heparinized sample. After 24 h washing in PBS 1X, the cell compatibility of the heparinized scaffolds was improved. In-vitro examination results exhibited human endothelial cell attachment and proliferation for 7 days of culture. (4) Conclusions: Our in-vitro analysis provided evidence for the scaffold’s ability to support endothelialization, which benefits long-term thromboresistance. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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13 pages, 3601 KiB  
Article
In Vitro Biocompatibility and Degradation Analysis of Mass-Produced Collagen Fibers
by Kiran M. Ali, Yihan Huang, Alaowei Y. Amanah, Nasif Mahmood, Taylor C. Suh and Jessica M. Gluck
Polymers 2022, 14(10), 2100; https://doi.org/10.3390/polym14102100 - 21 May 2022
Cited by 4 | Viewed by 2676
Abstract
Automation and mass-production are two of the many limitations in the tissue engineering industry. Textile fabrication methods such as electrospinning are used extensively in this field because of the resemblance of the extracellular matrix to the fiber structure. However, electrospinning has many limitations, [...] Read more.
Automation and mass-production are two of the many limitations in the tissue engineering industry. Textile fabrication methods such as electrospinning are used extensively in this field because of the resemblance of the extracellular matrix to the fiber structure. However, electrospinning has many limitations, including the ability to mass-produce, automate, and reproduce products. For this reason, this study evaluates the potential use of a traditional textile method such as spinning. Apart from mass production, these methods are also easy, efficient, and cost-effective. This study uses bovine-derived collagen fibers to create yarns using the traditional ring spinning method. The collagen yarns are proven to be biocompatible. Enzymatic biodegradability was also confirmed for its potential use in vivo. The results of this study prove the safety and efficacy of the material and the fabrication method. The material encourages higher cell proliferation and migration compared to tissue culture-treated plastic plates. The process is not only simple but is also streamlined and replicable, resulting in standardized products that can be reproduced. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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11 pages, 3168 KiB  
Article
Synthesis and In Vitro Characterization of Ascorbyl Palmitate-Loaded Solid Lipid Nanoparticles
by Maja Ledinski, Ivan Marić, Petra Peharec Štefanić, Iva Ladan, Katarina Caput Mihalić, Tanja Jurkin, Marijan Gotić and Inga Urlić
Polymers 2022, 14(9), 1751; https://doi.org/10.3390/polym14091751 - 26 Apr 2022
Cited by 5 | Viewed by 2409
Abstract
Antitumor applications of ascorbic acid (AA) and its oxidized form dehydroascorbic acid (DHA) can be quite challenging due to their instability and sensitivity to degradation in aqueous media. To overcome this obstacle, we have synthesized solid lipid nanoparticles loaded with ascorbyl palmitate (SLN-AP) [...] Read more.
Antitumor applications of ascorbic acid (AA) and its oxidized form dehydroascorbic acid (DHA) can be quite challenging due to their instability and sensitivity to degradation in aqueous media. To overcome this obstacle, we have synthesized solid lipid nanoparticles loaded with ascorbyl palmitate (SLN-AP) with variations in proportions of the polymer Pluronic F-68. SLNs were synthesized using the hot homogenization method, characterized by measuring the particle size, polydispersity, zeta potential and visualized by TEM. To investigate the cellular uptake of the SLN, we have incorporated coumarin-6 into the same SLN formulation and followed their successful uptake for 48 h. We have tested the cytotoxicity of the SLN formulations and free ascorbate forms, AA and DHA, on HEK 293 and U2OS cell lines by MTT assay. The SLN-AP in both formulations have a cytotoxic effect at lower concentrations when compared to ascorbate applied the form of AA or DHA. Better selectivity for targeting tumor cell line was observed with 3% Pluronic F-68. The antioxidative effect of the SLN-AP was observed as early as 1 h after the treatment with a small dose of ascorbate applied (5 µM). SLN-AP formulation with 3% Pluronic F-68 needs to be further optimized as an ascorbate carrier due to its intrinsic cytotoxicity. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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15 pages, 4089 KiB  
Article
A Study on the Correlation between the Oxidation Degree of Oxidized Sodium Alginate on Its Degradability and Gelation
by Hongcai Wang, Xiuqiong Chen, Yanshi Wen, Dongze Li, Xiuying Sun, Zhaowen Liu, Huiqiong Yan and Qiang Lin
Polymers 2022, 14(9), 1679; https://doi.org/10.3390/polym14091679 - 21 Apr 2022
Cited by 35 | Viewed by 4969
Abstract
Oxidized sodium alginate (OSA) is selected as an appropriate material to be extensively applied in regenerative medicine, 3D-printed/composite scaffolds, and tissue engineering for its excellent physicochemical properties and biodegradability. However, few literatures have systematically investigated the structure and properties of the resultant OSA [...] Read more.
Oxidized sodium alginate (OSA) is selected as an appropriate material to be extensively applied in regenerative medicine, 3D-printed/composite scaffolds, and tissue engineering for its excellent physicochemical properties and biodegradability. However, few literatures have systematically investigated the structure and properties of the resultant OSA and the effect of the oxidation degree (OD) of alginate on its biodegradability and gelation ability. Herein, we used NaIO4 as the oxidant to oxidize adjacent hydroxyl groups at the C-2 and C-3 positions on alginate uronic acid monomer to obtain OSA with various ODs. The structure and physicochemical properties of OSA were evaluated by Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H NMR), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), and thermogravimetric analysis (TGA). At the same time, gel permeation chromatography (GPC) and a rheometer were used to determine the hydrogel-forming ability and biodegradation performance of OSA. The results showed that the two adjacent hydroxyl groups of alginate uronic acid units were successfully oxidized to form the aldehyde groups; as the amount of NaIO4 increased, the OD of OSA gradually increased, the molecular weight decreased, the gelation ability continued to weaken, and degradation performance obviously rose. It is shown that OSA with various ODs could be prepared by regulating the molar ratio of NaIO4 and sodium alginate (SA), which could greatly broaden the application of OSA-based hydrogel in tissue engineering, controlled drug release, 3D printing, and the biomedical field. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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18 pages, 3683 KiB  
Article
A New Decellularization Protocol of Porcine Aortic Valves Using Tergitol to Characterize the Scaffold with the Biocompatibility Profile Using Human Bone Marrow Mesenchymal Stem Cells
by Marika Faggioli, Arianna Moro, Salman Butt, Martina Todesco, Deborah Sandrin, Giulia Borile, Andrea Bagno, Assunta Fabozzo, Filippo Romanato, Massimo Marchesan, Saima Imran and Gino Gerosa
Polymers 2022, 14(6), 1226; https://doi.org/10.3390/polym14061226 - 17 Mar 2022
Cited by 6 | Viewed by 3239
Abstract
The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has [...] Read more.
The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has a limited durability. In particular, current bioprosthetic valves have to be replaced after approximately 10 years; mechanical prostheses are more durable but require the administration of permanent anticoagulant therapy. With regard to pediatric patients, both mechanical and biological prosthetic valves have to be replaced due to their inability to follow patients’ growth. An alternative surgical substitute can be represented by the acellular porcine aortic valve that exhibits less immunogenic risk and a longer lifespan. In the present study, an efficient protocol for the removal of cells by using detergents, enzyme inhibitors, and hyper- and hypotonic shocks is reported. A new detergent (Tergitol) was applied to replace TX-100 with the aim to reduce toxicity and maximize ECM preservation. The structural integrity and efficient removal of cells and nuclear components were assessed by means of histology, immunofluorescence, and protein quantification; biomechanical properties were also checked by tensile tests. After decellularization, the acellular scaffold was sterilized with a standard protocol and repopulated with bone marrow mesenchymal stem cells to analyze its biocompatibility profile. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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17 pages, 10937 KiB  
Article
Bioactive Low Molecular Weight Keratin Hydrolysates for Improving Skin Wound Healing
by Laura Olariu, Brindusa Georgiana Dumitriu, Carmen Gaidau, Maria Stanca, Luiza Mariana Tanase, Manuela Diana Ene, Ioana-Rodica Stanculescu and Cristina Tablet
Polymers 2022, 14(6), 1125; https://doi.org/10.3390/polym14061125 - 11 Mar 2022
Cited by 7 | Viewed by 2673
Abstract
Keratin biomaterials with high molecular weights were intensively investigated but few are marketed due to complex methods of extraction and preparation and limited understanding of their influence on cells behavior. In this context the aim of this research was to elucidate decisive molecular [...] Read more.
Keratin biomaterials with high molecular weights were intensively investigated but few are marketed due to complex methods of extraction and preparation and limited understanding of their influence on cells behavior. In this context the aim of this research was to elucidate decisive molecular factors for skin homeostasis restoration induced by two low molecular weight keratin hydrolysates extracted and conditioned through a simple and green method. Two keratin hydrolysates with molecular weights of 3758 and 12,400 Da were physico-chemically characterized and their structure was assessed by circular dichroism (CD) and FTIR spectroscopy in view of bioactive potential identification. Other investigations were focused on several molecular factors: α1, α2 and β1 integrin mediated signals, cell cycle progression in pro-inflammatory conditions (TNFα/LPS stimulated keratinocytes and fibroblasts) and ICAM-1/VCAM-1 inhibition in human vascular endothelial cells. Flow cytometry techniques demonstrated a distinctive pattern of efficacy: keratin hydrolysates over-expressed α1 and α2 subunits, responsible for tight bounds between fibroblasts and collagen or laminin 1; both actives stimulated the epidermal turn-over and inhibited VCAM over-expression in pro-inflammatory conditions associated with bacterial infections. Our results offer mechanistic insights in wound healing signaling factors modulated by the two low molecular weight keratin hydrolysates which still preserve bioactive secondary structure. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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Review

Jump to: Research

25 pages, 2908 KiB  
Review
Poly(caprolactone)-b-poly(ethylene glycol)-Based Polymeric Micelles as Drug Carriers for Efficient Breast Cancer Therapy: A Systematic Review
by Siti Hajar Ahmad Shariff, Wan Khartini Wan Abdul Khodir, Shafida Abd Hamid, Muhammad Salahuddin Haris and Mohamad Wafiuddin Ismail
Polymers 2022, 14(22), 4847; https://doi.org/10.3390/polym14224847 - 10 Nov 2022
Cited by 8 | Viewed by 1950
Abstract
Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anti-cancer drugs due to the lack of tumour-targeting activity in conventional pharmaceuticals. Poly(caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles [...] Read more.
Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anti-cancer drugs due to the lack of tumour-targeting activity in conventional pharmaceuticals. Poly(caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles have attracted significant attention as a potential drug carrier intended for human use. Since their first discovery, the Food and Drug Administration (FDA)-approved polymers have been studied extensively for various biomedical applications, specifically cancer therapy. The application of PCL-PEG micelles in different cancer therapies has been recorded in countless research studies for their efficacy as drug cargos. However, systematic studies on the effectiveness of PCL-PEG micelles of specific cancers for pharmaceutical applications are still lacking. As breast cancer is reported as the most prevalent cancer worldwide, we aim to systematically review all available literature that has published research findings on the PCL-PEG-based micelles as drug cargo for therapy. We further discussed the preparation method and the anti-tumour efficacy of the micelles. Using a prearranged search string, Scopus and Science Direct were selected as the databases for the systematic searching strategy. Only eight of the 314 articles met the inclusion requirements and were used for data synthesis. From the review, all studies reported the efficiency of PCL-PEG-based micelles, which act as drug cargo for breast cancer therapy. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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18 pages, 3558 KiB  
Review
Chitosan-Based Biomaterials for Bone Tissue Engineering Applications: A Short Review
by Antonia Ressler
Polymers 2022, 14(16), 3430; https://doi.org/10.3390/polym14163430 - 22 Aug 2022
Cited by 50 | Viewed by 5649
Abstract
Natural bone tissue is composed of calcium-deficient carbonated hydroxyapatite as the inorganic phase and collagen type I as the main organic phase. The biomimetic approach of scaffold development for bone tissue engineering application is focused on mimicking complex bone characteristics. Calcium phosphates are [...] Read more.
Natural bone tissue is composed of calcium-deficient carbonated hydroxyapatite as the inorganic phase and collagen type I as the main organic phase. The biomimetic approach of scaffold development for bone tissue engineering application is focused on mimicking complex bone characteristics. Calcium phosphates are used in numerous studies as bioactive phases to mimic natural bone mineral. In order to mimic the organic phase, synthetic (e.g., poly(ε-caprolactone), polylactic acid, poly(lactide-co-glycolide acid)) and natural (e.g., alginate, chitosan, collagen, gelatin, silk) biodegradable polymers are used. However, as materials obtained from natural sources are accepted better by the human organism, natural polymers have attracted increasing attention. Over the last three decades, chitosan was extensively studied as a natural polymer suitable for biomimetic scaffold development for bone tissue engineering applications. Different types of chitosan-based biomaterials (e.g., molded macroporous, fiber-based, hydrogel, microspheres and 3D-printed) with specific properties for different regenerative applications were developed due to chitosan’s unique properties. This review summarizes the state-of-the-art of biomaterials for bone regeneration and relevant studies on chitosan-based materials and composites. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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25 pages, 2174 KiB  
Review
Current Advances in the Development of Hydrogel-Based Wound Dressings for Diabetic Foot Ulcer Treatment
by Viviana R. Güiza-Argüello, Víctor A. Solarte-David, Angie V. Pinzón-Mora, Jhair E. Ávila-Quiroga and Silvia M. Becerra-Bayona
Polymers 2022, 14(14), 2764; https://doi.org/10.3390/polym14142764 - 6 Jul 2022
Cited by 28 | Viewed by 6174
Abstract
Diabetic foot ulcers (DFUs) are one of the most prevalent complications associated with diabetes mellitus. DFUs are chronic injuries that often lead to non-traumatic lower extremity amputations, due to persistent infection and other ulcer-related side effects. Moreover, these complications represent a significant economic [...] Read more.
Diabetic foot ulcers (DFUs) are one of the most prevalent complications associated with diabetes mellitus. DFUs are chronic injuries that often lead to non-traumatic lower extremity amputations, due to persistent infection and other ulcer-related side effects. Moreover, these complications represent a significant economic burden for the healthcare system, as expensive medical interventions are required. In addition to this, the clinical treatments that are currently available have only proven moderately effective, evidencing a great need to develop novel strategies for the improved treatment of DFUs. Hydrogels are three-dimensional systems that can be fabricated from natural and/or synthetic polymers. Due to their unique versatility, tunability, and hydrophilic properties, these materials have been extensively studied for different types of biomedical applications, including drug delivery and tissue engineering applications. Therefore, this review paper addresses the most recent advances in hydrogel wound dressings for effective DFU treatment, providing an overview of current perspectives and challenges in this research field. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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