Research

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10 pages, 4598 KiB

Open AccessArticle

Amniotic Membrane Biopolymer for Regenerative Medicine

by Evgeny Milyudin, Larisa Teodorovna Volova, Ksenia E. Kuchuk, Elena V. Timchenko and Pavel E. Timchenko

Polymers 2023, 15(5), 1213; https://doi.org/10.3390/polym15051213 - 28 Feb 2023

Viewed by 1297

Abstract

Biopolymers based on the amniotic membrane compare favorably with synthetic materials in that, along with a specific 2D structure, they have biologically active properties. However, in recent years, there has been a tendency to perform decellularization of the biomaterial during the preparation of [...] Read more.

Biopolymers based on the amniotic membrane compare favorably with synthetic materials in that, along with a specific 2D structure, they have biologically active properties. However, in recent years, there has been a tendency to perform decellularization of the biomaterial during the preparation of the scaffold. In this study, we studied the microstructure of 157 samples and identified individual biological components in the manufacture of a medical biopolymer from an amniotic membrane using various methods. Group 1 had 55 samples, and the amniotic membrane was impregnated with glycerol and dried over silica gel. Group 2 had 48 samples, and the decellularized amniotic membrane was impregnated with glycerol followed by lyophilization, Group 3 had 44 samples, and the decellularized amniotic membrane without pre-impregnation with glycerol was subjected to lyophilization. Decellularization was performed by treatment with a low-frequency ultrasound at a frequency of 24–40 kHz in an ultrasonic bath. A morphological study using a light microscope and a scanning electron microscope showed the preservation of the structure of the biomaterial and more complete decellularization in samples subjected to lyophilization without prior impregnation with glycerol. The study of the Raman spectroscopy lines of a biopolymer made from a lyophilized amniotic membrane without preliminary impregnation with glycerin showed significant differences in the intensity of the spectral lines of amides, glycogen, and proline. Additionally, in these samples, the spectral lines of Raman scattering the characteristic of glycerol were not visualized; therefore, only biological substances characteristic of the native amniotic membrane have been preserved. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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20 pages, 1754 KiB

Open AccessArticle

The Fabrication of Gelatin–Elastin–Nanocellulose Composite Bioscaffold as a Potential Acellular Skin Substitute

by Ahmad Mus’ab Ahmad Hariza, Mohd Heikal Mohd Yunus, Mh Busra Fauzi, Jaya Kumar Murthy, Yasuhiko Tabata and Yosuke Hiraoka

Polymers 2023, 15(3), 779; https://doi.org/10.3390/polym15030779 - 03 Feb 2023

Cited by 2 | Viewed by 2104

Abstract

Gelatin usage in scaffold fabrication is limited due to its lack of enzymatic and thermal resistance, as well as its mechanical weakness. Hence, gelatin requires crosslinking and reinforcement with other materials. This study aimed to fabricate and characterise composite scaffolds composed of gelatin, [...] Read more.

Gelatin usage in scaffold fabrication is limited due to its lack of enzymatic and thermal resistance, as well as its mechanical weakness. Hence, gelatin requires crosslinking and reinforcement with other materials. This study aimed to fabricate and characterise composite scaffolds composed of gelatin, elastin, and cellulose nanocrystals (CNC) and crosslinked with genipin. The scaffolds were fabricated using the freeze-drying method. The composite scaffolds were composed of different concentrations of CNC, whereas scaffolds made of pure gelatin and a gelatin–elastin mixture served as controls. The physicochemical and mechanical properties of the scaffolds, and their cellular biocompatibility with human dermal fibroblasts (HDF), were evaluated. The composite scaffolds demonstrated higher porosity and swelling capacity and improved enzymatic resistance compared to the controls. Although the group with 0.5% (w/v) CNC recorded the highest pore size homogeneity, the diameters of most of the pores in the composite scaffolds ranged from 100 to 200 μm, which is sufficient for cell migration. Tensile strength analysis revealed that increasing the CNC concentration reduced the scaffolds’ stiffness. Chemical analyses revealed that despite chemical and structural alterations, both elastin and CNC were integrated into the gelatin scaffold. HDF cultured on the scaffolds expressed collagen type I and α-SMA proteins, indicating the scaffolds’ biocompatibility with HDF. Overall, the addition of elastin and CNC improved the properties of gelatin-based scaffolds. The composite scaffolds are promising candidates for an acellular skin substitute. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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23 pages, 7515 KiB

Open AccessArticle

Detection of Limbal Stem Cells Adhered to Melt Electrospun Silk Fibroin and Gelatin-Modified Polylactic Acid Scaffolds

by Emilija Zdraveva, Krešo Bendelja, Luka Bočkor, Tamara Dolenec and Budimir Mijović

Polymers 2023, 15(3), 777; https://doi.org/10.3390/polym15030777 - 03 Feb 2023

Cited by 4 | Viewed by 1510

Abstract

Limbal stem cells (LSCs) are of paramount importance in corneal epithelial tissue repair. The cornea becomes opaque in case of limbal stem cell deficiency (LSCD), which may cause serious damage to the ocular visual function. There are many techniques to restore damaged epithelium, [...] Read more.

Limbal stem cells (LSCs) are of paramount importance in corneal epithelial tissue repair. The cornea becomes opaque in case of limbal stem cell deficiency (LSCD), which may cause serious damage to the ocular visual function. There are many techniques to restore damaged epithelium, one of which is the transplantation of healthy cultured LSCs, usually onto a human amniotic membrane or onto bio-based engineered scaffolds in recent years. In this study, melt electrospun polylactic acid (PLA) was modified by silk fibroin or gelatin and further cultured with LSCs originating from three different donors. In terms of physicochemical properties, both modifications slightly increased PLA scaffold porosity (with a significantly larger pore area for the PLA/gelatin) and improved the scaffolds’ swelling percentage, as well as their biodegradation rate. In terms of the scaffold application function, the aim was to detect/visualize whether LSCs adhered to the scaffolds and to further determine cell viability (total number), as well as to observe p63 and CK3 expressions in the LSCs. LSCs were attached to the surface of microfibers, showing flattened conformations or 3D spheres in the formation of colonies or agglomerations, respectively. All scaffolds showed the ability to bind the cells onto the surface of individual microfibers (PLA and PLA/gelatin), or in between the microfibers (PLA/silk fibroin), with the latter showing the most intense red fluorescence of the stained cells. All scaffolds proved to be biocompatible, while the PLA/silk fibroin scaffolds showed the highest 98% viability of 2.9 × 10⁶ LSCs, with more than 98% of p63 and less than 20% of CK3 expressions in the LSCs, thus confirming the support of their growth, proliferation and corneal epithelial differentiation. The results show the potential of these bio-engineered scaffolds to be used as an alternative clinical approach. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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17 pages, 3243 KiB

Open AccessArticle

Regeneration of Osteochondral Defects by Combined Delivery of Synovium-Derived Mesenchymal Stem Cells, TGF-β1 and BMP-4 in Heparin-Conjugated Fibrin Hydrogel

by Madina Sarsenova, Yerik Raimagambetov, Assel Issabekova, Miras Karzhauov, Gulshakhar Kudaibergen, Zhanar Akhmetkarimova, Arman Batpen, Yerlan Ramankulov and Vyacheslav Ogay

Polymers 2022, 14(24), 5343; https://doi.org/10.3390/polym14245343 - 07 Dec 2022

Cited by 4 | Viewed by 1905

Abstract

The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising [...] Read more.

The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising therapeutic strategy for osteochondral defects regeneration. In this study, we fabricated a heparin-conjugated fibrin (HCF) hydrogel with synovium-derived mesenchymal stem cells (SDMSCs), transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-4 (BMP-4) to repair osteochondral defects in a rabbit model. An in vitro study showed that HCF hydrogel exhibited good biocompatibility, a slow degradation rate and sustained release of TGF-β1 and BMP-4 over 4 weeks. Macroscopic and histological evaluations revealed that implantation of HCF hydrogel with SDMSCs, TGF-β1 and BMP-4 significantly enhanced the regeneration of hyaline cartilage and the subchondral bone plate in osteochondral defects within 12 weeks compared to hydrogels with SDMSCs or growth factors alone. Thus, these data suggest that combined delivery of SDMSCs with TGF-β1 and BMP-4 in HCF hydrogel may synergistically enhance the therapeutic efficacy of osteochondral defect repair of the knee joints. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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15 pages, 2716 KiB

Open AccessArticle

3D-Printed Pectin/Carboxymethyl Cellulose/ZnO Bio-Inks: Comparative Analysis with the Solution Casting Method

by Yeon Ho Kim, Ruchir Priyadarshi, Jin-Wook Kim, Jangwhan Kim, Denis G. Alekseev and Jong-Whan Rhim

Polymers 2022, 14(21), 4711; https://doi.org/10.3390/polym14214711 - 03 Nov 2022

Cited by 8 | Viewed by 2352

Abstract

Bio-inks consisting of pectin (Pec), carboxymethyl cellulose (CMC), and ZnO nanoparticles (ZnO) were used to prepare films by solution casting and 3D-printing methods. Field emission scanning electron microscopy (FE-SEM) was conducted to observe that the surface of samples made by 3D bioprinter was [...] Read more.

Bio-inks consisting of pectin (Pec), carboxymethyl cellulose (CMC), and ZnO nanoparticles (ZnO) were used to prepare films by solution casting and 3D-printing methods. Field emission scanning electron microscopy (FE-SEM) was conducted to observe that the surface of samples made by 3D bioprinter was denser and more compact than the solution cast samples. In addition, Pec/CMC/ZnO made by 3D-bioprinter (Pec/CMC/ZnO-3D) revealed enhanced water vapor barrier, hydrophobicity, and mechanical properties. Pec/CMC/ZnO-3D also showed strong antimicrobial activity within 12 h against S. aureus and E. coli O157: H7 bacterial strains compared to the solution cast films. Further, the nanocomposite bio-inks used for 3D printing did not show cytotoxicity towards normal human dermal fibroblast (NDFB) cells but enhanced the fibroblast proliferation with increasing exposure concentration of the sample. The study provided two important inferences. Firstly, the 3D bioprinting method can be an alternative, better, and more practical method for fabricating biopolymer film instead of solution casting, which is the main finding of this work defining its novelty. Secondly, the Pec/CMC/ZnO can potentially be used as 3D bio-inks to fabricate functional films or scaffolds and biomedical applications. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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18 pages, 5438 KiB

Open AccessArticle

PLA-PEG Implant as a Drug Delivery System in Glaucoma Surgery: Experimental Study

by Viktoriya N. Germanova, Elena V. Karlova, Larisa T. Volova, Andrey V. Zolotarev, Viktoriya V. Rossinskaya, Ivan D. Zakharov, Aleksandr R. Korigodskiy, Violetta V. Boltovskaya, Irina F. Nefedova and Mariya V. Radaykina

Polymers 2022, 14(16), 3419; https://doi.org/10.3390/polym14163419 - 21 Aug 2022

Cited by 4 | Viewed by 1614

Abstract

Excessive postoperative scarring halts the effectiveness of glaucoma surgery and still remains a challenging problem. The purpose of this study was to develop a PLA-PEG-based drug delivery system with cyclosporine A or everolimus for wound healing modulation. Methods: PLA-PEG implants saturation with cyclosporine [...] Read more.

Excessive postoperative scarring halts the effectiveness of glaucoma surgery and still remains a challenging problem. The purpose of this study was to develop a PLA-PEG-based drug delivery system with cyclosporine A or everolimus for wound healing modulation. Methods: PLA-PEG implants saturation with cyclosporine A or everolimus as well as their further in vitro release were analyzed. Anti-proliferative activity and cytotoxicity of the immunosuppressants were studied in vitro using human Tenon’s fibroblasts. Thirty-six rabbits underwent glaucoma filtration surgery with the application of sham implants or samples saturated with cyclosporine A or everolimus. The follow-up period was six months. A morphological study of the surgery area was also performed at seven days, one, and six months post-op. Results: PLA-PEG implants revealed a satisfactory ability to cumulate either cyclosporine A or everolimus. The most continuous period of cyclosporine A and everolimus desorption was 7 and 13 days, respectively. Immunosuppressants demonstrated marked anti-proliferative effect regarding human Tenon’s fibroblasts without signs of cytotoxicity at concentrations provided by the implants. Application of PLA-PEG implants saturated with immunosuppressants improved in vivo glaucoma surgery outcomes. Conclusions: Prolonged delivery of either cyclosporine A or everolimus by means of PLA-PEG implants represents a promising strategy of wound healing modulation in glaucoma filtration surgery. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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15 pages, 5775 KiB

Open AccessArticle

Recombinant Spidroin Microgel as the Base of Cell-Engineered Constructs Mediates Liver Regeneration in Rats

by Murat Shagidulin, Nina Onishchenko, Anastasiia Grechina, Alla Nikolskaya, Mikhail Krasheninnikov, Aleksey Lyundup, Elena Volkova, Natalia Mogeiko, Artem Venediktov, Gennadii Piavchenko, Lubov Davydova, Alla Ramonova, Vladimir Bogush and Sergey Gautier

Polymers 2022, 14(15), 3179; https://doi.org/10.3390/polym14153179 - 04 Aug 2022

Viewed by 1461

Abstract

Aim: In this study, we seek to check if recombinant spidroin rS1/9 is applicable for cell-engineering construct development. Novel technologies of cell and tissue engineering are relevant for chronic liver failure management. Liver regeneration may represent one of the possible treatment options [...] Read more.

Aim: In this study, we seek to check if recombinant spidroin rS1/9 is applicable for cell-engineering construct development. Novel technologies of cell and tissue engineering are relevant for chronic liver failure management. Liver regeneration may represent one of the possible treatment options if a cell-engineered construct (CEC) is used. Nowadays, one can see the continuous study of various matrices to create an appropriate CEC. Materials and Methods: We have adhered allogenic liver cells and multipotent mesenchymal bone marrow stem cells (MMSC BM) to a microgel with recombinant spidroin rS1/9. Then we have studied the developed implantable CEC in a rat model (n = 80) of chronic liver failure achieved by prolonged poisoning with carbon tetrachloride. Results: Our results demonstrate that the CECs change the values of biochemical tests and morphological parameters in chronic liver failure in rats. Conclusion: We consider there to be a positive effect from the microgel-based CECs with recombinant spidroin rS1/9 in the treatment of chronic liver failure. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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25 pages, 63914 KiB

Open AccessArticle

Fabrication and Evaluation of Electrospun Silk Fibroin/Halloysite Nanotube Biomaterials for Soft Tissue Regeneration

by Soheila Mohammadzadehmoghadam, Catherine F. LeGrand, Chee-Wai Wong, Beverley F. Kinnear, Yu Dong and Deirdre R. Coombe

Polymers 2022, 14(15), 3004; https://doi.org/10.3390/polym14153004 - 25 Jul 2022

Cited by 2 | Viewed by 1943

Abstract

The production of nanofibrous materials for soft tissue repair that resemble extracellular matrices (ECMs) is challenging. Electrospinning uniquely produces scaffolds resembling the ultrastructure of natural ECMs. Herein, electrospinning was used to fabricate Bombyx mori silk fibroin (SF) and SF/halloysite nanotube (HNT) composite scaffolds. [...] Read more.

The production of nanofibrous materials for soft tissue repair that resemble extracellular matrices (ECMs) is challenging. Electrospinning uniquely produces scaffolds resembling the ultrastructure of natural ECMs. Herein, electrospinning was used to fabricate Bombyx mori silk fibroin (SF) and SF/halloysite nanotube (HNT) composite scaffolds. Different HNT loadings were examined, but 1 wt% HNTs enhanced scaffold hydrophilicity and water uptake capacity without loss of mechanical strength. The inclusion of 1 wt% HNTs in SF scaffolds also increased the scaffold’s thermal stability without altering the molecular structure of the SF, as revealed by thermogravimetric analyses and Fourier transform infrared spectroscopy (FTIR), respectively. SF/HNT 1 wt% composite scaffolds better supported the viability and spreading of 3T3 fibroblasts and the differentiation of C2C12 myoblasts into aligned myotubes. These scaffolds coated with decellularised ECM from 3T3 cells or primary human dermal fibroblasts (HDFs) supported the growth of primary human keratinocytes. However, SF/HNT 1 wt% composite scaffolds with HDF-derived ECM provided the best microenvironment, as on these, keratinocytes formed intact monolayers with an undifferentiated, basal cell phenotype. Our data indicate the merits of SF/HNT 1 wt% composite scaffolds for applications in soft tissue repair and the expansion of primary human keratinocytes for skin regeneration. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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Review

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39 pages, 2996 KiB

Open AccessReview

3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks

by Larisa T. Volova, Gennadiy P. Kotelnikov, Igor Shishkovsky, Dmitriy B. Volov, Natalya Ossina, Nikolay A. Ryabov, Aleksey V. Komyagin, Yeon Ho Kim and Denis G. Alekseev

Polymers 2023, 15(12), 2695; https://doi.org/10.3390/polym15122695 - 15 Jun 2023

Cited by 3 | Viewed by 1861

Abstract

The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and [...] Read more.

The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and significant worsening in the quality of life. Due to its structure and function, articular (hyaline) cartilage is the most susceptible to damage. Articular cartilage is a non-vascular tissue with constrained self-regeneration capabilities. Additionally, treatment methods, which have proven efficacy in stopping its degradation and promoting regeneration, still do not exist. Conservative treatment and physical therapy only relieve the symptoms associated with cartilage destruction, and traditional surgical interventions to repair defects or endoprosthetics are not without serious drawbacks. Thus, articular cartilage damage remains an urgent and actual problem requiring the development of new treatment approaches. The emergence of biofabrication technologies, including three-dimensional (3D) bioprinting, at the end of the 20th century, allowed reconstructive interventions to get a second wind. Three-dimensional bioprinting creates volume constraints that mimic the structure and function of natural tissue due to the combinations of biomaterials, living cells, and signal molecules to create. In our case—hyaline cartilage. Several approaches to articular cartilage biofabrication have been developed to date, including the promising technology of 3D bioprinting. This review represents the main achievements of such research direction and describes the technological processes and the necessary biomaterials, cell cultures, and signal molecules. Special attention is given to the basic materials for 3D bioprinting—hydrogels and bioinks, as well as the biopolymers underlying the indicated products. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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29 pages, 1162 KiB

Open AccessReview

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

by Ilya L. Tsiklin, Aleksey V. Shabunin, Alexandr V. Kolsanov and Larisa T. Volova

Polymers 2022, 14(15), 3222; https://doi.org/10.3390/polym14153222 - 08 Aug 2022

Cited by 20 | Viewed by 3120

Abstract

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and [...] Read more.

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical translation of BTE requires overcoming a number of significant challenges. Currently, insufficient vascularization is the critical limitation for viability of the bone tissue-engineered construct. Furthermore, efficacy and safety of the scaffolds cell-seeding and exogenous growth factors administration are still controversial. The in vivo bioreactor principle (IVB) is an exceptionally promising concept for the in vivo bone tissue regeneration in a predictable patient-specific manner. This concept is based on the self-regenerative capacity of the human body, and combines flap prefabrication and axial vascularization strategies. Multiple experimental studies on in vivo BTE strategies presented in this review demonstrate the efficacy of this approach. Routine clinical application of the in vivo bioreactor principle is the future direction of BTE; however, it requires further investigation for overcoming some significant limitations. Full article

(This article belongs to the Special Issue Biopolymers for Regenerative Medicine Applications)

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