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Polymer Scaffolds for Biomedical Applications 2021

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

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 44032

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Dr. Matthias Schnabelrauch

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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
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Dear Colleagues,

Polymeric scaffolds derived from natural and synthetic sources play a crucial role in many clinical methods aimed at repairing or regrowing human tissue damaged by disease or trauma. Driven by the ability to regenerate ever more complex tissues and organ components, the demands on polymer scaffold materials and manufacturing processes have also grown. Scaffolds with defined molecular structures, controlled degradation behavior, 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. Furthermore, the surface properties of polymers have been 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 abovementioned 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; and cell-based production systems for sera and vaccines.

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

Dr. Matthias Schnabelrauch
Guest Editor

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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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Related Special Issues

Polymer Scaffolds for Biomedical Applications 2020 in Molecules (21 articles)
Polymer Scaffolds for Biomedical Applications III in Molecules (10 articles)

Published Papers (11 papers)

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Research

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20 pages, 2706 KiB

Open AccessArticle

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 - 1 Oct 2021

Cited by 4 | Viewed by 3718

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 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

Open AccessArticle

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 28 | Viewed by 3581

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, 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

Open AccessArticle

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 2349

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. 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

Open AccessArticle

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 11 | Viewed by 3516

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 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

Open AccessArticle

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 18 | Viewed by 3502

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 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

Open AccessArticle

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 13 | Viewed by 3228

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 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

Open AccessArticle

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 - 2 Apr 2021

Cited by 28 | Viewed by 4635

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 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

Open AccessArticle

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 9 | Viewed by 2775

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 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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27 pages, 2755 KiB

Open AccessFeature PaperReview

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 65 | Viewed by 9066

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 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

Open AccessReview

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 24 | Viewed by 3324

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 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

Open AccessReview

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 - 5 May 2021

Cited by 18 | Viewed by 3184

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 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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