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Polymer Scaffolds for Biomedical Applications 2020
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Polymer Scaffolds for Biomedical Applications 2020

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Macromolecular Chemistry".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 36299

Special Issue Editor

Dr. Matthias Schnabelrauch

E-Mail Website
Guest Editor
INNOVENT e. V., Department of Biomaterials, Pruessingstrasse 27B, D-07745 Jena, Germany
Interests: biomaterials; biopolymers; polymer synthesis; biodegradable polymers; polysaccharides; glycosaminoglycans; hydrogels; hybrid materials; tissue engineering; electrospinning; antibacterial polymers; material–cell interactions; surface modification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polymeric scaffolds derived from natural and synthetic sources play a crucial role in many clinical methods to repair or re-grow human tissue damaged by disease or trauma. Driven by medical progress to be able to regenerate even more complex tissues or organ components, the demands on polymer scaffold materials and manufacturing processes have also grown. Scaffolds with defined molecular structures, controlled degradation behavior, and mechanical properties that can be adapted to the respective tissue and the ability of materials to specifically interact with cells and bioactive molecules play an important role here. At the same time, powerful techniques for the production of complex and reproducible scaffold and carrier structures have been established and the surface properties of polymers adapted to the needs of the cells by means of efficient modification processes.

This Special Issue will focus on recent innovative developments with regard to the preparation of highly cytocompatible polymer materials and the establishment of high-performance manufacturing and modification processes for polymer and polymer composite scaffolds.

Topics are not limited to the above-mentioned studies but can cover all research areas concerning polymeric scaffolds for biomedical applications including transfer systems for therapeutic nucleic acids; release systems for bioactive molecules, such as growth factors to stimulate tissue regeneration; cell culture systems for organ-on-a-chip models; bio-imaging devices; or cell-based production systems for sera and vaccines.

Considering your prominent contribution in this interesting research field, I would like to cordially invite you to submit an article to this Special Issue. Full research papers, communications, and review articles are welcome.

Dr. Matthias Schnabelrauch
Guest Editor

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. Molecules 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

  • Polymeric scaffolds
  • Natural and synthetic polymers
  • Scaffold fabrication techniques
  • Regenerative medicine
  • Tissue engineering
  • Additive manufacturing processes
  • Hydrogels
  • Nano and micro fibers
  • Porous materials
  • Polymer–cell interactions

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Published Papers (21 papers)

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20 pages, 2706 KiB  
Article
TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid
by Junwen Shan, Thomas Böck, Thorsten Keller, Leonard Forster, Torsten Blunk, Jürgen Groll and Jörg Teßmar
Molecules 2021, 26(19), 5963; https://doi.org/10.3390/molecules26195963 - 01 Oct 2021
Cited by 4 | Viewed by 3028
Abstract
Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different [...] Read more.
Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer’s backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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18 pages, 10363 KiB  
Article
Fabrication and Evaluation of Alginate/Bacterial Cellulose Nanocrystals–Chitosan–Gelatin Composite Scaffolds
by Zhengyue Li, Xiuqiong Chen, Chaoling Bao, Chang Liu, Chunyang Liu, Dongze Li, Huiqiong Yan and Qiang Lin
Molecules 2021, 26(16), 5003; https://doi.org/10.3390/molecules26165003 - 18 Aug 2021
Cited by 22 | Viewed by 2855
Abstract
It is common knowledge that pure alginate hydrogel is more likely to have weak mechanical strength, a lack of cell recognition sites, extensive swelling and uncontrolled degradation, and thus be unable to satisfy the demands of the ideal scaffold. To address these problems, [...] Read more.
It is common knowledge that pure alginate hydrogel is more likely to have weak mechanical strength, a lack of cell recognition sites, extensive swelling and uncontrolled degradation, and thus be unable to satisfy the demands of the ideal scaffold. To address these problems, we attempted to fabricate alginate/bacterial cellulose nanocrystals-chitosan-gelatin (Alg/BCNs-CS-GT) composite scaffolds using the combined method involving the incorporation of BCNs in the alginate matrix, internal gelation through the hydroxyapatite-d-glucono-δ-lactone (HAP-GDL) complex, and layer-by-layer (LBL) electrostatic assembly of polyelectrolytes. Meanwhile, the effect of various contents of BCNs on the scaffold morphology, porosity, mechanical properties, and swelling and degradation behavior was investigated. The experimental results showed that the fabricated Alg/BCNs-CS-GT composite scaffolds exhibited regular 3D morphologies and well-developed pore structures. With the increase in BCNs content, the pore size of Alg/BCNs-CS-GT composite scaffolds was gradually reduced from 200 μm to 70 μm. Furthermore, BCNs were fully embedded in the alginate matrix through the intermolecular hydrogen bond with alginate. Moreover, the addition of BCNs could effectively control the swelling and biodegradation of the Alg/BCNs-CS-GT composite scaffolds. Furthermore, the in vitro cytotoxicity studies indicated that the porous fiber network of BCNs could fully mimic the extracellular matrix structure, which promoted the adhesion and spreading of MG63 cells and MC3T3-E1 cells on the Alg/BCNs-CS-GT composite scaffolds. In addition, these cells could grow in the 3D-porous structure of composite scaffolds, which exhibited good proliferative viability. Based on the effect of BCNs on the cytocompatibility of composite scaffolds, the optimum BCNs content for the Alg/BCNs-CS-GT composite scaffolds was 0.2% (w/v). On the basis of good merits, such as regular 3D morphology, well-developed pore structure, controlled swelling and biodegradation behavior, and good cytocompatibility, the Alg/BCNs-CS-GT composite scaffolds may exhibit great potential as the ideal scaffold in the bone tissue engineering field. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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13 pages, 5110 KiB  
Article
Oxygen Plasma Technology-Assisted Preparation of Three-Dimensional Reduced Graphene Oxide/Polypyrrole/Strontium Composite Scaffold for Repair of Bone Defects Caused by Osteoporosis
by Xiaoxue Mai, Zebiao Kang, Na Wang, Xiaoli Qin, Weibo Xie and Fuxiang Song
Molecules 2021, 26(15), 4451; https://doi.org/10.3390/molecules26154451 - 23 Jul 2021
Cited by 2 | Viewed by 1941
Abstract
Repairs of bone defects caused by osteoporosis have always relied on bone tissue engineering. However, the preparation of composite tissue engineering scaffolds with a three-dimensional (3D) macroporous structure poses huge challenges in achieving osteoconduction and osteoinduction for repairing bone defects caused by osteoporosis. [...] Read more.
Repairs of bone defects caused by osteoporosis have always relied on bone tissue engineering. However, the preparation of composite tissue engineering scaffolds with a three-dimensional (3D) macroporous structure poses huge challenges in achieving osteoconduction and osteoinduction for repairing bone defects caused by osteoporosis. In the current study, a three-dimensional macroporous (150–300 μm) reduced graphene oxide/polypyrrole composite scaffold modified by strontium (Sr) (3D rGO/PPY/Sr) was successfully prepared using the oxygen plasma technology-assisted method, which is simple, safe, and inexpensive. The findings of the MTT assay and AO/EB fluorescence double staining showed that 3D rGO/PPY/Sr has a good biocompatibility and effectively promoted MC3T3-E1 cell proliferation. Furthermore, the ALP assay and alizarin red staining showed that 3D rGO/PPY/Sr increased the expression levels of ALP activity and the formation of calcified nodules. The desirable biocompatibility, osteoconduction, and osteoinduction abilities, assure that the 3D macroporous rGO/PPY/Sr composite scaffold offers promising potential for use in the repair of bone defects caused by osteoporosis in bone tissue engineering. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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14 pages, 3731 KiB  
Article
Crosslinked Silk Fibroin/Gelatin/Hyaluronan Blends as Scaffolds for Cell-Based Tissue Engineering
by Anongnart Duangpakdee, Chavee Laomeephol, Depicha Jindatip, Peerapat Thongnuek, Juthamas Ratanavaraporn and Siriporn Damrongsakkul
Molecules 2021, 26(11), 3191; https://doi.org/10.3390/molecules26113191 - 26 May 2021
Cited by 9 | Viewed by 2978
Abstract
3D porous scaffolds fabricated from binary and ternary blends of silk fibroin (SF), gelatin (G), and hyaluronan (HA) and crosslinked by the carbodiimide coupling reaction were developed. Water-stable scaffolds can be obtained after crosslinking, and the SFG and SFGHA samples were stable in [...] Read more.
3D porous scaffolds fabricated from binary and ternary blends of silk fibroin (SF), gelatin (G), and hyaluronan (HA) and crosslinked by the carbodiimide coupling reaction were developed. Water-stable scaffolds can be obtained after crosslinking, and the SFG and SFGHA samples were stable in cell culture medium up to 10 days. The presence of HA in the scaffolds with appropriate crosslinking conditions greatly enhanced the swellability. The microarchitecture of the freeze-dried scaffolds showed high porosity and interconnectivity. In particular, the pore size was significantly larger with an addition of HA. Biological activities of NIH/3T3 fibroblasts seeded on SFG and SFGHA scaffolds revealed that both scaffolds were able to support cell adhesion and proliferation of a 7-day culture. Furthermore, cell penetration into the scaffolds can be observed due to the interconnected porous structure of the scaffolds and the presence of bioactive materials which could attract the cells and support cell functions. The higher cell number was noticed in the SFGHA samples, possibly due to the HA component and the larger pore size which could improve the microenvironment for fibroblast adhesion, proliferation, and motility. The developed scaffolds from ternary blends showed potential in their application as 3D cell culture substrates in fibroblast-based tissue engineering. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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16 pages, 17701 KiB  
Article
Bacteriostatic Behavior of PLA-BaTiO3 Composite Fibers Synthesized by Centrifugal Spinning and Subjected to Aging Test
by Francesco Boschetto, Hoan Ngoc Doan, Phu Phong Vo, Matteo Zanocco, Kenta Yamamoto, Wenliang Zhu, Tetsuya Adachi, Kenji Kinashi, Elia Marin and Giuseppe Pezzotti
Molecules 2021, 26(10), 2918; https://doi.org/10.3390/molecules26102918 - 14 May 2021
Cited by 16 | Viewed by 2824
Abstract
The present work investigated the effect of Polylactic acid (PLA) fibers produced by centrifugal spinning with incorporated BaTiO3 particles to improve their bacteriostatic behavior. The PLA matrix and three composites, presenting three different amounts of fillers, were subjected to UV/O3 treatment [...] Read more.
The present work investigated the effect of Polylactic acid (PLA) fibers produced by centrifugal spinning with incorporated BaTiO3 particles to improve their bacteriostatic behavior. The PLA matrix and three composites, presenting three different amounts of fillers, were subjected to UV/O3 treatment monitoring the possible modifications that occurred over time. The morphological and physical properties of the surfaces were characterized by different microscopic techniques, contact angle, and surface potential measurements. Subsequently, the samples were tested in vitro with human dermal fibroblasts (HDF) to verify the cytotoxicity of the substrates. No significant differences between the PLA matrix and composites emerged; the high hydrophobicity of the fibers, derived by the polymer structure, represented an obstacle limiting the fibroblast attachment. Samples underwent bacterial exposure (Staphylococcus epidermidis) for 12 and 24 h. Increasing the concentration of BT, the number of living bacteria and their distribution decreased in comparison with the PLA matrix suggesting an effect of the inorganic filler, which generates a neutralization effect leading to reactive oxygen species (ROS) generation and subsequently to bacterial damages. These results suggest that the barium titanate (BT) fillers clearly improve the antibacterial properties of PLA fibers after aging tests made before bacterial exposure, representing a potential candidate in the creation of composites for medical applications. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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17 pages, 5024 KiB  
Article
Mineralization of Phosphorylated Fish Skin Collagen/Mangosteen Scaffolds as Potential Materials for Bone Tissue Regeneration
by Eduardo P. Milan, Murilo Á. V. Rodrigues, Virginia C. A. Martins, Ana M. G. Plepis, Thomas Fuhrmann-Lieker and Marilia M. Horn
Molecules 2021, 26(10), 2899; https://doi.org/10.3390/molecules26102899 - 13 May 2021
Cited by 11 | Viewed by 2678
Abstract
In this study, a potential hard tissue substitute was mimicked using collagen/mangosteen porous scaffolds. Collagen was extracted from Tilapia fish skin and mangosteen from the waste peel of the respective fruit. Sodium trimetaphosphate was used for the phosphorylation of these scaffolds to improve [...] Read more.
In this study, a potential hard tissue substitute was mimicked using collagen/mangosteen porous scaffolds. Collagen was extracted from Tilapia fish skin and mangosteen from the waste peel of the respective fruit. Sodium trimetaphosphate was used for the phosphorylation of these scaffolds to improve the nucleation sites for the mineralization process. Phosphate groups were incorporated in the collagen structure as confirmed by their attenuated total reflection Fourier transform infrared (ATR-FTIR) bands. The phosphorylation and mangosteen addition increased the thermal stability of the collagen triple helix structure, as demonstrated by differential scanning calorimetry (DSC) and thermogravimetry (TGA) characterizations. Mineralization was successfully achieved, and the presence of calcium phosphate was visualized by scanning electron microscopy (SEM). Nevertheless, the porous structure was maintained, which is an essential characteristic for the desired application. The deposited mineral was amorphous calcium phosphate, as confirmed by energy dispersive X-ray spectroscopy (EDX) results. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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22 pages, 6468 KiB  
Article
Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds
by Arie Wibowo, Gusti U. N. Tajalla, Maradhana A. Marsudi, Glen Cooper, Lia A.T.W. Asri, Fengyuan Liu, Husaini Ardy and Paulo J.D.S. Bartolo
Molecules 2021, 26(7), 2042; https://doi.org/10.3390/molecules26072042 - 02 Apr 2021
Cited by 20 | Viewed by 3728
Abstract
Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability [...] Read more.
Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs’ properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO3. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10−3 S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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16 pages, 7048 KiB  
Article
In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process
by Fernando Bento Cunha, Karina Torres Pomini, Ana Maria de Guzzi Plepis, Virgínia da Conceição Amaro Martins, Eduardo Gomes Machado, Renato de Moraes, Marcelo de Azevedo e Souza Munhoz, Michela Vanessa Ribeiro Machado, Marco Antonio Hungaro Duarte, Murilo Priori Alcalde, Daniela Vieira Buchaim, Rogério Leone Buchaim, Victor Augusto Ramos Fernandes, Eliana de Souza Bastos Mazuqueli Pereira, André Antonio Pelegrine and Marcelo Rodrigues da Cunha
Molecules 2021, 26(6), 1598; https://doi.org/10.3390/molecules26061598 - 13 Mar 2021
Cited by 7 | Viewed by 2341
Abstract
Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages [...] Read more.
Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25). Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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17 pages, 4858 KiB  
Article
Change in Collagen Fibril Diameter Distribution of Bovine Anterior Cruciate Ligament upon Injury Can Be Mimicked in a Nanostructured Scaffold
by Zhuldyz Beisbayeva, Ainur Zhanbassynova, Gulzada Kulzhanova, Fariza Mukasheva and Cevat Erisken
Molecules 2021, 26(5), 1204; https://doi.org/10.3390/molecules26051204 - 24 Feb 2021
Cited by 6 | Viewed by 2750
Abstract
More than 200,000 people are suffering from Anterior Cruciate Ligament (ACL) related injuries each year in the US. There is an unmet clinical demand for improving biological attachment between grafts and the host tissue in addition to providing mechanical support. For biological graft [...] Read more.
More than 200,000 people are suffering from Anterior Cruciate Ligament (ACL) related injuries each year in the US. There is an unmet clinical demand for improving biological attachment between grafts and the host tissue in addition to providing mechanical support. For biological graft integration, it is important to provide a physiologically feasible environment for the host cells to enable them to perform their duties. However, behavior of cells during ACL healing and the mechanism of ACL healing is not fully understood partly due to the absence of appropriate environment to test cell behavior both in vitro and in vivo. This study aims at (i) investigating the change in fibril diameter of bovine ACL tissue upon injury and (ii) fabricating nanofiber-based scaffolds to represent the morphology and structure of healthy and injured ACL tissues. We hypothesized that distribution and mean diameter of ACL fibrils will be altered upon injury. Findings revealed that the collagen fibril diameter distribution of bovine ACL changed from bimodal to unimodal upon injury with subsequent decrease in mean diameter. Polycaprolactone (PCL) scaffold fiber diameter distribution exhibited similar bimodal and unimodal distribution behavior to qualitatively represent the cases of healthy and injured ACL, respectively. The native ACL tissue demonstrated comparable modulus values only with the aligned bimodal PCL scaffolds. There was significant difference between mechanical properties of aligned bimodal and unaligned unimodal PCL scaffolds. We believe that the results obtained from measurements of diameter of collagen fibrils of native bovine ACL tissue can serve as a benchmark for scaffold design. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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21 pages, 6706 KiB  
Article
A Tuneable, Photocurable, Poly(Caprolactone)-Based Resin for Tissue Engineering—Synthesis, Characterisation and Use in Stereolithography
by Jonathan Field, John W. Haycock, Fiona M. Boissonade and Frederik Claeyssens
Molecules 2021, 26(5), 1199; https://doi.org/10.3390/molecules26051199 - 24 Feb 2021
Cited by 24 | Viewed by 3974
Abstract
Stereolithography is a useful additive manufacturing technique for the production of scaffolds for tissue engineering. Here we present a tuneable, easy-to-manufacture, photocurable resin for use in stereolithography, based on the widely used biomaterial, poly(caprolactone) (PCL). PCL triol was methacrylated to varying degrees and [...] Read more.
Stereolithography is a useful additive manufacturing technique for the production of scaffolds for tissue engineering. Here we present a tuneable, easy-to-manufacture, photocurable resin for use in stereolithography, based on the widely used biomaterial, poly(caprolactone) (PCL). PCL triol was methacrylated to varying degrees and mixed with photoinitiator to produce a photocurable prepolymer resin, which cured under UV light to produce a cytocompatible material. This study demonstrates that poly(caprolactone) methacrylate (PCLMA) can be produced with a range of mechanical properties and degradation rates. By increasing the degree of methacrylation (DM) of the prepolymer, the Young’s modulus of the crosslinked PCLMA could be varied from 0.12–3.51 MPa. The accelerated degradation rate was also reduced from complete degradation in 17 days to non-significant degradation in 21 days. The additive manufacturing capabilities of the resin were demonstrated by the production of a variety of different 3D structures using micro-stereolithography. Here, β-carotene was used as a novel, cytocompatible photoabsorber and enabled the production of complex geometries by giving control over cure depth. The PCLMA presented here offers an attractive, tuneable biomaterial for the production of tissue engineering scaffolds for a wide range of applications. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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17 pages, 6291 KiB  
Article
Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer
by Bruna Botteon Della Coletta, Thiago Borges Jacob, Luana Aparecida de Carvalho Moreira, Karina Torres Pomini, Daniela Vieira Buchaim, Rachel Gomes Eleutério, Eliana de Souza Bastos Mazuqueli Pereira, Domingos Donizeti Roque, Marcelie Priscila de Oliveira Rosso, João Vitor Tadashi Cosin Shindo, Marco Antônio Húngaro Duarte, Murilo Priori Alcalde, Rui Seabra Ferreira Júnior, Benedito Barraviera, Jefferson Aparecido Dias, Jesus Carlos Andreo and Rogério Leone Buchaim
Molecules 2021, 26(4), 847; https://doi.org/10.3390/molecules26040847 - 05 Feb 2021
Cited by 20 | Viewed by 2704
Abstract
The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG ( [...] Read more.
The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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20 pages, 4813 KiB  
Article
A Novel Resorbable Composite Material Containing Poly(ester-co-urethane) and Precipitated Calcium Carbonate Spherulites for Bone Augmentation—Development and Preclinical Pilot Trials
by Claudia Rode, Ralf Wyrwa, Juergen Weisser, Matthias Schnabelrauch, Marijan Vučak, Stefanie Grom, Frank Reinauer, Adrian Stetter, Karl Andreas Schlegel and Rainer Lutz
Molecules 2021, 26(1), 102; https://doi.org/10.3390/molecules26010102 - 28 Dec 2020
Viewed by 2220
Abstract
Polyurethanes have the potential to impart cell-relevant properties like excellent biocompatibility, high and interconnecting porosity and controlled degradability into biomaterials in a relatively simple way. In this context, a biodegradable composite material made of an isocyanate-terminated co-oligoester prepolymer and precipitated calcium carbonated spherulites [...] Read more.
Polyurethanes have the potential to impart cell-relevant properties like excellent biocompatibility, high and interconnecting porosity and controlled degradability into biomaterials in a relatively simple way. In this context, a biodegradable composite material made of an isocyanate-terminated co-oligoester prepolymer and precipitated calcium carbonated spherulites (up to 60% w/w) was synthesized and investigated with regard to an application as bone substitute in dental and orthodontic application. After foaming the composite material, a predominantly interconnecting porous structure is obtained, which can be easily machined. The compressive strength of the foamed composites increases with raising calcium carbonate content and decreasing calcium carbonate particle size. When stored in an aqueous medium, there is a decrease in pressure stability of the composite, but this decrease is smaller the higher the proportion of the calcium carbonate component is. In vitro cytocompatibility studies of the foamed composites on MC3T3-E1 pre-osteoblasts revealed an excellent cytocompatibility. The in vitro degradation behaviour of foamed composite is characterised by a continuous loss of mass, which is slower with higher calcium carbonate contents. In a first pre-clinical pilot trial the foamed composite bone substitute material (fcm) was successfully evaluated in a model of vertical augmentation in an established animal model on the calvaria and on the lateral mandible of pigs. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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28 pages, 11604 KiB  
Article
Two-Photon Polymerized Poly(2-Ethyl-2-Oxazoline) Hydrogel 3D Microstructures with Tunable Mechanical Properties for Tissue Engineering
by Steffen Czich, Thomas Wloka, Holger Rothe, Jürgen Rost, Felix Penzold, Maximilian Kleinsteuber, Michael Gottschaldt, Ulrich S. Schubert and Klaus Liefeith
Molecules 2020, 25(21), 5066; https://doi.org/10.3390/molecules25215066 - 31 Oct 2020
Cited by 14 | Viewed by 2771
Abstract
The main task of tissue engineering (TE) is to reproduce, replicate, and mimic all kinds of tissues in the human body. Nowadays, it has been proven useful in TE to mimic the natural extracellular matrix (ECM) by an artificial ECM (scaffold) based on [...] Read more.
The main task of tissue engineering (TE) is to reproduce, replicate, and mimic all kinds of tissues in the human body. Nowadays, it has been proven useful in TE to mimic the natural extracellular matrix (ECM) by an artificial ECM (scaffold) based on synthetic or natural biomaterials to regenerate the physiological tissue/organ architecture and function. Hydrogels have gained interest in the TE community because of their ability to absorb water similar to physiological tissues, thus mechanically simulating the ECM. In this work, we present a novel hydrogel platform based on poly(2-ethyl-2-oxazoline)s, which can be processed to 3D microstructures via two-photon polymerization (2PP) with tunable mechanical properties using monomers and crosslinker with different degrees of polymerization (DP) for future applications in TE. The ideal parameters (laser power and writing speed) for optimal polymerization via 2PP were obtained using a specially developed evaluation method in which the obtained structures were binarized and compared to the computer-aided design (CAD) model. This evaluation was performed for each composition. We found that it was possible to tune the mechanical properties not only by application of different laser parameters but also by mixing poly(2-ethyl-2-oxazoline)s with different chain lengths and variation of the crosslink density. In addition, the swelling behavior of different fabricated hydrogels were investigated. To gain more insight into the viscoelastic behavior of different fabricated materials, stress relaxation tests via nanoindentation experiments were performed. These new hydrogels can be processed to 3D microstructures with high structural integrity using optimal laser parameter settings, opening a wide range of application properties in TE for this material platform. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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21 pages, 3476 KiB  
Article
Influence of PVA Molecular Weight and Concentration on Electrospinnability of Birch Bark Extract-Loaded Nanofibrous Scaffolds Intended for Enhanced Wound Healing
by Francis Kamau Mwiiri and Rolf Daniels
Molecules 2020, 25(20), 4799; https://doi.org/10.3390/molecules25204799 - 19 Oct 2020
Cited by 27 | Viewed by 3215
Abstract
Triterpenes from the outer bark of birch (TE) are known for various pharmacological effects including enhanced wound healing. Apart from an already authorized oleogel, electrospun nanofiber mats containing these triterpenes in a polyvinyl alcohol (PVA) matrix appear to be an advantageous application form. [...] Read more.
Triterpenes from the outer bark of birch (TE) are known for various pharmacological effects including enhanced wound healing. Apart from an already authorized oleogel, electrospun nanofiber mats containing these triterpenes in a polyvinyl alcohol (PVA) matrix appear to be an advantageous application form. The effects of PVA molecular weight and concentration on the fiber morphology have been investigated. Three different molecular weights of PVA ranging from 67 to 186 kDa were used. The concentration of PVA was varied from 5 to 20 wt%. Polymer solutions were blended with colloidal dispersions of birch bark extract at a weight ratio of 60:40 (wt.%). The estimated viscosity of polymer solutions was directly linked to their concentration and molecular weight. In addition, both pure and blended solutions showed viscoelastic properties with a dominant viscous response in the bulk. Fiber morphology was confirmed using scanning electron microscopy (SEM). Both polymer concentration and molecular weight were found to be significant factors affecting the diameter of the fibers. Fiber diameter increased with a higher molecular weight and polymer concentration as more uniform fibers were obtained using PVA of higher molecular weight (146–186 kDa). In vitro drug release and ex vivo permeation studies indicated a faster drug release of betulin from electrospun scaffolds with lower PVA molecular weight. Our research suggests that the fabricated TE-loaded PVA electrospun dressings represent potential delivery systems of TE for wound care applications. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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30 pages, 7556 KiB  
Article
Fabrication and Plasma Surface Activation of Aligned Electrospun PLGA Fiber Fleeces with Improved Adhesion and Infiltration of Amniotic Epithelial Stem Cells Maintaining their Teno-inductive Potential
by Mohammad El Khatib, Annunziata Mauro, Ralf Wyrwa, Miriam Di Mattia, Maura Turriani, Oriana Di Giacinto, Björn Kretzschmar, Thomas Seemann, Luca Valbonetti, Paolo Berardinelli, Matthias Schnabelrauch, Barbara Barboni and Valentina Russo
Molecules 2020, 25(14), 3176; https://doi.org/10.3390/molecules25143176 - 11 Jul 2020
Cited by 12 | Viewed by 4231
Abstract
Electrospun PLGA microfibers with adequate intrinsic physical features (fiber alignment and diameter) have been shown to boost teno-differentiation and may represent a promising solution for tendon tissue engineering. However, the hydrophobic properties of PLGA may be adjusted through specific treatments to improve cell [...] Read more.
Electrospun PLGA microfibers with adequate intrinsic physical features (fiber alignment and diameter) have been shown to boost teno-differentiation and may represent a promising solution for tendon tissue engineering. However, the hydrophobic properties of PLGA may be adjusted through specific treatments to improve cell biodisponibility. In this study, electrospun PLGA with highly aligned microfibers were cold atmospheric plasma (CAP)-treated by varying the treatment exposure time (30, 60, and 90 s) and the working distance (1.3 and 1.7 cm) and characterized by their physicochemical, mechanical and bioactive properties on ovine amniotic epithelial cells (oAECs). CAP improved the hydrophilic properties of the treated materials due to the incorporation of new oxygen polar functionalities on the microfibers’ surface especially when increasing treatment exposure time and lowering working distance. The mechanical properties, though, were affected by the treatment exposure time where the optimum performance was obtained after 60 s. Furthermore, CAP treatment did not alter oAECs’ biocompatibility and improved cell adhesion and infiltration onto the microfibers especially those treated from a distance of 1.3 cm. Moreover, teno-inductive potential of highly aligned PLGA electrospun microfibers was maintained. Indeed, cells cultured onto the untreated and CAP treated microfibers differentiated towards the tenogenic lineage expressing tenomodulin, a mature tendon marker, in their cytoplasm. In conclusion, CAP treatment on PLGA microfibers conducted at 1.3 cm working distance represent the optimum conditions to activate PLGA surface by improving their hydrophilicity and cell bio-responsiveness. Since for tendon tissue engineering purposes, both high cell adhesion and mechanical parameters are crucial, PLGA treated for 60 s at 1.3 cm was identified as the optimal construct. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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Review

Jump to: Research

27 pages, 2755 KiB  
Review
Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine
by David T. Wu, Jose G. Munguia-Lopez, Ye Won Cho, Xiaolu Ma, Vivian Song, Zhiyue Zhu and Simon D. Tran
Molecules 2021, 26(22), 7043; https://doi.org/10.3390/molecules26227043 - 22 Nov 2021
Cited by 50 | Viewed by 6965
Abstract
Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad [...] Read more.
Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad range of applications in biomedical engineering and regenerative medicine functioning as tissue engineering scaffolds, carriers for cell-based therapies, and biomedical devices for delivery of drugs and biologics. The focus of this review is to discuss the properties and clinical indications of polymeric scaffold materials and extracellular matrix technologies for DOC regenerative medicine. More specifically, this review outlines the key properties, advantages and drawbacks of natural polymers including alginate, cellulose, chitosan, silk, collagen, gelatin, fibrin, laminin, decellularized extracellular matrix, and hyaluronic acid, as well as synthetic polymers including polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly (ethylene glycol) (PEG), and Zwitterionic polymers. This review highlights key clinical applications of polymeric scaffolding materials to repair and/or regenerate various DOC tissues. Particularly, polymeric materials used in clinical procedures are discussed including alveolar ridge preservation, vertical and horizontal ridge augmentation, maxillary sinus augmentation, TMJ reconstruction, periodontal regeneration, periodontal/peri-implant plastic surgery, regenerative endodontics. In addition, polymeric scaffolds application in whole tooth and salivary gland regeneration are discussed. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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21 pages, 2875 KiB  
Review
Glycosaminoglycan-Based Cryogels as Scaffolds for Cell Cultivation and Tissue Regeneration
by Annika Wartenberg, Jürgen Weisser and Matthias Schnabelrauch
Molecules 2021, 26(18), 5597; https://doi.org/10.3390/molecules26185597 - 15 Sep 2021
Cited by 20 | Viewed by 2744
Abstract
Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in [...] Read more.
Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in this way correspond to the native extracellular matrix (ECM) in terms of both composition and molecular structure. Due to their specific structural feature and in addition to an excellent biocompatibility, GAG-based cryogels have several advantages over traditional GAG-hydrogels. This includes macroporous, interconnective pore structure, robust, elastic, and shape-memory-like mechanical behavior, as well as injectability for many GAG-based cryogels. After addressing the cryogelation process, the fabrication of GAG-based cryogels and known principles of GAG monomer crosslinking are discussed. Finally, an overview of specific GAG-based cryogels in biomedicine, mainly as polymeric scaffold material in tissue regeneration and tissue engineering-related controlled release of bioactive molecules and cells, is provided. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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12 pages, 7557 KiB  
Review
Polymer Scaffolds for Biomedical Applications in Peripheral Nerve Reconstruction
by Meng Zhang, Ci Li, Li-Ping Zhou, Wei Pi and Pei-Xun Zhang
Molecules 2021, 26(9), 2712; https://doi.org/10.3390/molecules26092712 - 05 May 2021
Cited by 16 | Viewed by 2697
Abstract
The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits [...] Read more.
The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2021)
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27 pages, 4218 KiB  
Review
Nanomaterials for Biomedical Applications: Production, Characterisations, Recent Trends and Difficulties
by Mostafa Mabrouk, Diganta B. Das, Zeinab A. Salem and Hanan H. Beherei
Molecules 2021, 26(4), 1077; https://doi.org/10.3390/molecules26041077 - 18 Feb 2021
Cited by 76 | Viewed by 5009
Abstract
Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current [...] Read more.
Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current knowledge based on the design and production of nanomaterials. Considerations of size, shape, surface charge and microstructures are important factors in this regard as they affect the performance of nanoparticles (NPs). These parameters are also found to be dependent on their synthesis methods. The characterisation techniques that have been used for the investigation of these nanomaterials are relatively different in their concepts, sample preparation methods and obtained results. Consequently, this review article aims to carry out an in-depth discussion on the recent trends on nanomaterials for biomedical engineering, with a particular emphasis on the choices of the nanomaterials, preparation methods/instruments and characterisations techniques used for designing of nanomaterials. Key applications of these nanomaterials, such as tissue regeneration, medication delivery and wound healing, are also discussed briefly. Covering this knowledge gap will result in a better understanding of the role of nanomaterial design and subsequent larger-scale applications in terms of both its potential and difficulties. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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22 pages, 4050 KiB  
Review
Microbial Polyhydroxyalkanoates Granules: An Approach Targeting Biopolymer for Medical Applications and Developing Bone Scaffolds
by Moushmi Goswami, Pavni Rekhi, Mousumi Debnath and Seeram Ramakrishna
Molecules 2021, 26(4), 860; https://doi.org/10.3390/molecules26040860 - 06 Feb 2021
Cited by 41 | Viewed by 4575
Abstract
Microbial polyhydroxyalkanoates (PHA) are proteinaceous storage granules ranging from 100 nm to 500 nm. Bacillus sp. serve as unique bioplastic sources of short-chain length and medium-chain length PHA showcasing properties such as biodegradability, thermostability, and appreciable mechanical strength. The PHA can be enhanced [...] Read more.
Microbial polyhydroxyalkanoates (PHA) are proteinaceous storage granules ranging from 100 nm to 500 nm. Bacillus sp. serve as unique bioplastic sources of short-chain length and medium-chain length PHA showcasing properties such as biodegradability, thermostability, and appreciable mechanical strength. The PHA can be enhanced by adding functional groups to make it a more industrially useful biomaterial. PHA blends with hydroxyapatite to form nanocomposites with desirable features of compressibility. The reinforced matrices result in nanocomposites that possess significantly improved mechanical and thermal properties both in solid and melt states along with enhanced gas barrier properties compared to conventional filler composites. These superior qualities extend the polymeric composites’ applications to aggressive environments where the neat polymers are likely to fail. This nanocomposite can be used in different industries as nanofillers, drug carriers for packaging essential hormones and microcapsules, etc. For fabricating a bone scaffold, electrospun nanofibrils made from biocomposite of hydroxyapatite and polyhydroxy butyrate, a form of PHA, can be incorporated with the targeted tissue. The other methods for making a polymer scaffold, includes gas foaming, lyophilization, sol–gel, and solvent casting method. In this review, PHA as a sustainable eco-friendly NextGen biomaterial from bacterial sources especially Bacillus cereus, and its application for fabricating bone scaffold using different strategies for bone regeneration have been discussed. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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24 pages, 2631 KiB  
Review
Recent Advances in Scaffolding from Natural-Based Polymers for Volumetric Muscle Injury
by Tamrin Nuge, Ziqian Liu, Xiaoling Liu, Bee Chin Ang, Andri Andriyana, Hendrik Simon Cornelis Metselaar and Md Enamul Hoque
Molecules 2021, 26(3), 699; https://doi.org/10.3390/molecules26030699 - 29 Jan 2021
Cited by 15 | Viewed by 3911
Abstract
Volumetric Muscle Loss (VML) is associated with muscle loss function and often untreated and considered part of the natural sequelae of trauma. Various types of biomaterials with different physical and properties have been developed to treat VML. However, much work remains yet to [...] Read more.
Volumetric Muscle Loss (VML) is associated with muscle loss function and often untreated and considered part of the natural sequelae of trauma. Various types of biomaterials with different physical and properties have been developed to treat VML. However, much work remains yet to be done before the scaffolds can pass from the bench to the bedside. The present review aims to provide a comprehensive summary of the latest developments in the construction and application of natural polymers-based tissue scaffolding for volumetric muscle injury. Here, the tissue engineering approaches for treating volumetric muscle loss injury are highlighted and recent advances in cell-based therapies using various sources of stem cells are elaborated in detail. An overview of different strategies of tissue scaffolding and their efficacy on skeletal muscle cells regeneration and migration are presented. Furthermore, the present paper discusses a wide range of natural polymers with a special focus on proteins and polysaccharides that are major components of the extracellular matrices. The natural polymers are biologically active and excellently promote cell adhesion and growth. These bio-characteristics justify natural polymers as one of the most attractive options for developing scaffolds for muscle cell regeneration. Full article
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Applications 2020)
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