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Polymers
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Biopolymer-Based Biomimetic Scaffolds
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Biopolymer-Based Biomimetic Scaffolds

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

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 15023

Special Issue Editors

Dr. Chiara Emma Campiglio

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Guest Editor
Department of Management, Information and Production Engineering, Università degli Studi di Bergamo, Bergamo, Italy
Interests: biomaterials for tissue engineering; organ-on-chip; lung toxicology; kidney tissue engineering
Special Issues, Collections and Topics in MDPI journals
Dr. Sílvia J. Bidarra

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INEB-NEWTherapies Group, Laboratório Associado IBMC-INEB Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
Interests: materials science; biochemistry, genetics and molecular biology engineering; chemical engineering
Special Issues, Collections and Topics in MDPI journals
Dr. Thomas Distler

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Guest Editor
Formerly: Department of Materials Science and Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Interests: biomaterials; hydrogels; protein-based biomaterials; tissue engineering; electroconductive hydrogels; 3D printing; neural regeneration; mechanobiology; complex mechanical hydrogel and tissue properties; cell–material interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As is widely known, tissue engineering offers a unique alternative to current clinical treatments. With the aim of developing a complex living-tissue replacement, concerted efforts must be focused on creating extracellular-matrix-mimicking biomaterials that encourage interactions with host cells to unlock the body’s innate powers of organization and self-repair.

There are several technologies available for the fabrication of biomimetic scaffolds that focus on the use of a substance innately able (or engineered) to assume a desirable form that can be applied to both synthesize a 3D cellular microenvironment for cell accommodation and guide new tissue formation. Moreover, the identification of a material able to maintain its structure and integrity for predictable periods of time can ensure new tissue formation and maturation. Among the materials used in tissue engineering, naturally occurring biopolymers are often chosen as they show high biocompatibility, a favorable pro-remodeling host immune response and an instructive micro-environment for tissue remodeling. Their ability to mimic the  chemical properties of native extracellular matrix represents a great advantage that allows the fabrication of biomimetic scaffolds for the evaluation of cellular responses to material cues, providing tools for the in vitro modeling of disease and the treatment of patients using precision medicine. 

This Special Issue covers current research (original research papers, review articles and short communications) that focuses on the development and characterization of innovative biomimetic scaffolds made of naturally occurring polymers, which are used to recapitulate tissue formation and repair mechanisms within a 3D functional microenvironment.

Dr. Chiara Emma Campiglio
Dr. Sílvia J. Bidarra
Dr. Thomas Distler
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

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

Keywords

  • natural polymers
  • biomaterials
  • biomimetic structure
  • scaffold
  • tissue engineering
  • biopolymer
  • biocompatibility
  • cell–material interaction

Published Papers (9 papers)

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Research

Jump to: Review

19 pages, 3048 KiB  
Article
Tuning the Topography of Dynamic 3D Scaffolds through Functional Protein Wrinkled Coatings
by Elizabeth Oguntade, Daniel Fougnier, Sadie Meyer, Kerrin O’Grady, Autumn Kudlack and James H. Henderson
Polymers 2024, 16(5), 609; https://doi.org/10.3390/polym16050609 - 23 Feb 2024
Viewed by 841
Abstract
Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling [...] Read more.
Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling work on three-dimensional (3D) structures has been limited. To enable wrinkle formation on architecturally complex, biomimetic 3D structures, here, we report a simple, low-cost experimental wrinkling approach that combines natural silk fibroin films with a recently developed advanced manufacturing technique for programming strain in complex 3D shape–memory polymer (SMP) scaffolds. By systematically investigating the influence of SMP programmed strain magnitude, silk film thickness, and aqueous media on wrinkle morphology and stability, we reveal how to generate and tune silk wrinkles on the micron and sub-micron scale. We find that increasing SMP programmed strain magnitude increases wavelength and decreases amplitudes of silk wrinkled topographies, while increasing silk film thickness increases wavelength and amplitude. Silk wrinkles persist after 24 h in cell culture medium. Wrinkled topographies demonstrate high cell viability and attachment. These findings suggest the potential for fabricating biomimetic cellular microenvironments that can advance understanding and control of cell–material interactions in engineering tissue constructs. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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14 pages, 7853 KiB  
Article
Electrospun Polycaprolactone Membranes Expanded with Chitosan Granules for Cell Infiltration
by Tânia Vieira, Ana Margarida Rebelo, João Paulo Borges, Célia Henriques and Jorge Carvalho Silva
Polymers 2024, 16(4), 527; https://doi.org/10.3390/polym16040527 - 15 Feb 2024
Viewed by 555
Abstract
The small pore size of electrospun membranes prevents their use as three-dimensional scaffolds. In this work, we produced polycaprolactone (PCL) electrospun fibrous membranes with expanded pores by incorporating chitosan (CS) granules into the PCL solution. Scanning electron microscopy images confirmed the presence of [...] Read more.
The small pore size of electrospun membranes prevents their use as three-dimensional scaffolds. In this work, we produced polycaprolactone (PCL) electrospun fibrous membranes with expanded pores by incorporating chitosan (CS) granules into the PCL solution. Scanning electron microscopy images confirmed the presence of the CS granules embedded in the PCL fibers, creating an open structure. Tensile testing results showed that the addition of CS decreased both Young’s modulus and the yield stress, but co-electrospun membranes (PCL fibers blended with CS-containing PCL fibers) exhibited higher values compared to single electrospun membranes (CS-containing PCL fibers). Human fibroblasts adhered to and proliferated on all scaffolds. Nuclear staining revealed that cells populated the entire scaffold when CS granules were present, while in PCL membranes, cells were mostly limited to the surface due to the small pore size. Overall, our findings demonstrate that electrospun membranes containing CS granules have sufficiently large pores to facilitate fibroblast infiltration without compromising the mechanical stability of the structure. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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16 pages, 3315 KiB  
Article
Evaluation of the Modification Effects of Heparin/Dalteparin on Silk Fibroin Structure and Physical Properties for Skin Wound Healing
by Rikako Hama and Yasumoto Nakazawa
Polymers 2024, 16(3), 321; https://doi.org/10.3390/polym16030321 - 24 Jan 2024
Viewed by 691
Abstract
We have developed a functionalized silk fibroin (BSF) that can serve as an improved fundamental material for dressings by specifically capturing growth factors secreted during the healing process and supplying them to cells accumulated in the wound area to enhance the tissue regeneration [...] Read more.
We have developed a functionalized silk fibroin (BSF) that can serve as an improved fundamental material for dressings by specifically capturing growth factors secreted during the healing process and supplying them to cells accumulated in the wound area to enhance the tissue regeneration efficiency. When considering the design of heparin-modified BSF, there is a difficulty with binding to high-molecular-weight polysaccharides without disrupting the hydrophobic crystalline structure of the BSF. In this study, a low-molecular-weight pharmaceutical heparin, dalteparin, was selected and cross-linked with the tyrosine residue presence in the BSF non-crystalline region. When targeting 3D porous applications like nanofiber sheets, as it is crucial not only to enhance biological activity but also to improve handling by maintaining stability in water and mechanical strength, a trade-off between improved cell affinity and reduced mechanical strength depending on crystalline structure was evaluated. The use of dalteparin maintained the mechanical strength better than unfractionated heparin by reducing the effect on disturbing BSF recrystallization. Film surface hydrophilicity and cell proliferation induction were significantly higher in the dalteparin group. For BSF functionalization, using purified heparin was an effective approach that achieved a balance between preserving the mechanical properties and induction of tissue regeneration, offering the potential for various forms in the future. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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22 pages, 8592 KiB  
Article
Biocompatibility of ABS and PLA Polymers with Dental Pulp Stem Cells Enhance Their Potential Biomedical Applications
by Fabiane Barchiki, Letícia Fracaro, Alejandro Correa Dominguez, Alexandra Cristina Senegaglia, Isadora May Vaz, Paulo Soares, Sérgio Adriane Bezerra de Moura and Paulo Roberto Slud Brofman
Polymers 2023, 15(24), 4629; https://doi.org/10.3390/polym15244629 - 06 Dec 2023
Cited by 1 | Viewed by 871
Abstract
Polylactic Acid (PLA) and Acrylonitrile–Butadiene–Styrene (ABS) are commonly used polymers in 3D printing for biomedical applications. Dental Pulp Stem Cells (DPSCs) are an accessible and proliferative source of stem cells with significant differentiation potential. Limited knowledge exists regarding the biocompatibility and genetic safety [...] Read more.
Polylactic Acid (PLA) and Acrylonitrile–Butadiene–Styrene (ABS) are commonly used polymers in 3D printing for biomedical applications. Dental Pulp Stem Cells (DPSCs) are an accessible and proliferative source of stem cells with significant differentiation potential. Limited knowledge exists regarding the biocompatibility and genetic safety of ABS and PLA when in contact with DPSCs. This study aimed to investigate the impact of PLA and ABS on the adhesion, proliferation, osteogenic differentiation, genetic stability, proteomics, and immunophenotypic profile of DPSCs. A total of three groups, 1- DPSC-control, 2- DPSC+ABS, and 3- DPSC+PLA, were used in in vitro experiments to evaluate cell morphology, proliferation, differentiation capabilities, genetic stability, proteomics (secretome), and immunophenotypic profiles regarding the interaction between DPSCs and polymers. Both ABS and PLA supported the adhesion and proliferation of DPSCs without exhibiting significant cytotoxic effects and maintaining the capacity for osteogenic differentiation. Genetic stability, proteomics, and immunophenotypic profiles were unaltered in DPSCs post-contact with these polymers, highlighting their biosafety. Our findings suggest that ABS and PLA are biocompatible with DPSCs and demonstrate potential in dental or orthopedic applications; the choice of the polymer will depend on the properties required in treatment. These promising results stimulate further studies to explore the potential therapeutic applications in vivo using prototyped polymers in personalized medicine. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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15 pages, 5441 KiB  
Article
Properties of Resorbable Conduits Based on Poly(L-Lactide) Nanofibers and Chitosan Fibers for Peripheral Nerve Regeneration
by Nurjemal A. Tagandurdyyeva, Maxim A. Trube, Igor’ O. Shemyakin, Denis N. Solomitskiy, German V. Medvedev, Elena N. Dresvyanina, Yulia A. Nashchekina, Elena M. Ivan’kova, Irina P. Dobrovol’skaya, Almaz M. Kamalov, Elena G. Sukhorukova, Olga A. Moskalyuk and Vladimir E. Yudin
Polymers 2023, 15(15), 3323; https://doi.org/10.3390/polym15153323 - 07 Aug 2023
Cited by 5 | Viewed by 911
Abstract
New tubular conduits have been developed for the regeneration of peripheral nerves and the repair of defects that are larger than 3 cm. The conduits consist of a combination of poly(L-lactide) nanofibers and chitosan composite fibers with chitin nanofibrils. In vitro studies were [...] Read more.
New tubular conduits have been developed for the regeneration of peripheral nerves and the repair of defects that are larger than 3 cm. The conduits consist of a combination of poly(L-lactide) nanofibers and chitosan composite fibers with chitin nanofibrils. In vitro studies were conducted to assess the biocompatibility of the conduits using human embryonic bone marrow stromal cells (FetMSCs). The studies revealed good adhesion and differentiation of the cells on the conduits just one day after cultivation. Furthermore, an in vivo study was carried out to evaluate motor-coordination disorders using the sciatic nerve functional index (SFI) assessment. The presence of chitosan monofibers and chitosan composite fibers with chitin nanofibrils in the conduit design increased the regeneration rate of the sciatic nerve, with an SFI value ranging from 76 to 83. The degree of recovery of nerve conduction was measured by the amplitude of M-response, which showed a 46% improvement. The conduit design imitates the oriented architecture of the nerve, facilitates electrical communication between the damaged nerve’s ends, and promotes the direction of nerve growth, thereby increasing the regeneration rate. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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15 pages, 3925 KiB  
Article
Synthetic Heparan Sulfate Mimetic Polymer Enhances Corneal Nerve Regeneration and Wound Healing after Experimental Laser Ablation Injury in Mice
by Ignacio Alcalde, Cristina Sánchez-Fernández, Susana Del Olmo-Aguado, Carla Martín, Céline Olmiere, Enol Artime, Luis M. Quirós and Jesús Merayo-Lloves
Polymers 2022, 14(22), 4921; https://doi.org/10.3390/polym14224921 - 15 Nov 2022
Cited by 2 | Viewed by 1436
Abstract
(1) Background: Abnormal corneal wound healing compromises visual acuity and can lead to neuropathic pain. Conventional treatments usually fail to restore the injured corneal tissue. In this study, we evaluated the effectiveness of a synthetic heparan sulfate mimetic polymer (HSmP) in a mouse [...] Read more.
(1) Background: Abnormal corneal wound healing compromises visual acuity and can lead to neuropathic pain. Conventional treatments usually fail to restore the injured corneal tissue. In this study, we evaluated the effectiveness of a synthetic heparan sulfate mimetic polymer (HSmP) in a mouse model of corneal wound healing. (2) Methods: A surgical laser ablation affecting the central cornea and subbasal nerve plexus of mice was used as a model of the wound-healing assay. Topical treatment with HSmP was contrasted to its vehicle and a negative control (BSS). Corneal repair was studied using immunofluorescence to cell proliferation (Ki67), apoptosis (TUNEL assay), myofibroblast transformation (αSMA), assembly of epithelial cells (E-cadherin) and nerve regeneration (β-tubulin III). (3) Results: At the end of the treatment, normal epithelial cytoarchitecture and corneal thickness were achieved in HSmP-treated animals. HSmP treatment reduced myofibroblast occurrence compared to eyes irrigated with vehicle (p < 0.01) or BSS (p < 0.001). The HSmP group showed 50% more intraepithelial nerves than the BSS or vehicle groups. Only HSmP-treated corneas improved the visual quality to near transparent. (4) Conclusions: These results suggest that HSmP facilitates the regeneration of the corneal epithelium and innervation, as well as restoring transparency and reducing myofibroblast scarring after laser experimental injury. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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20 pages, 3430 KiB  
Article
A Biomimetic Nonwoven-Reinforced Hydrogel for Spinal Cord Injury Repair
by Ben Golland, Joanne L. Tipper, Richard M. Hall, Giuseppe Tronci and Stephen J. Russell
Polymers 2022, 14(20), 4376; https://doi.org/10.3390/polym14204376 - 17 Oct 2022
Cited by 3 | Viewed by 1683
Abstract
In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue [...] Read more.
In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue regeneration and tailor mechanical properties. This work studies the effects of an aligned electrospun nonwoven of P11-8—enriched poly(ε-caprolactone) (PCL) fibres, integrated with a photo-crosslinked hydrogel of glycidylmethacrylated collagen (collagen-GMA), on neurite extension. Mechanical properties of collagen-GMA hydrogel in compression and shear were recorded, along with cell viability. Collagen-GMA hydrogels showed J-shaped stress–strain curves in compression, mimicking native spinal cord tissue. For hydrogels prepared with a 0.8-1.1 wt.% collagen-GMA concentration, strain at break values were 68 ± 1–81 ± 1% (±SE); maximum stress values were 128 ± 9–311 ± 18 kPa (±SE); and maximum force values were 1.0 ± 0.1–2.5 ± 0.1 N (±SE). These values closely mimicked the compression values for feline and porcine tissue in the literature, especially those for 0.8 wt.%. Complex shear modulus values fell in the range 345–2588 Pa, with the lower modulus hydrogels in the range optimal for neural cell survival and growth. Collagen-GMA hydrogel provided an environment for homogenous and three-dimensional cell encapsulation, and high cell viability of 84 ± 2%. Combination of the aligned PCL/P11-8 electrospun nonwoven and collagen-GMA hydrogel retained fibre alignment and pore structure, respectively, and promoted aligned neurite extension of PC12 cells. Thus, it is possible to conclude that scaffolds with mechanical properties that both closely mimic native spinal cord tissue and are optimal for neural cells can be produced, which also promote aligned tissue regeneration when the benefits of hydrogels and electrospun nonwovens are combined. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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Review

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35 pages, 5905 KiB  
Review
Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering
by Jun Chen, Di Zhang, Lin-Ping Wu and Ming Zhao
Polymers 2023, 15(9), 2015; https://doi.org/10.3390/polym15092015 - 24 Apr 2023
Cited by 3 | Viewed by 3621
Abstract
Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a [...] Read more.
Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a promising alternative treatment for damaged or occlusive vessels. Large-scale tubular grafts, which can match arteries, arterioles, and venules, as well as meso- and microscale vasculature to alleviate ischemia or prevascularized engineered tissues, have been developed. In this review, materials and techniques for engineering tubular scaffolds and vasculature at all levels are discussed. Examples of vascularized tissue engineering in bone, peripheral nerves, and the heart are also provided. Finally, the current challenges are discussed and the perspectives on future developments in biofunctional engineered vessels are delineated. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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24 pages, 16374 KiB  
Review
Drug-Loaded Chitosan Scaffolds for Periodontal Tissue Regeneration
by Gamal Abdel Nasser Atia, Hany K. Shalaby, Mehrukh Zehravi, Mohamed Mohamady Ghobashy, Hager Abdel Nasser Attia, Zubair Ahmad, Farhat S. Khan, Abhijit Dey, Nobendu Mukerjee, Athanasios Alexiou, Md. Habibur Rahman, Joanna Klepacka and Agnieszka Najda
Polymers 2022, 14(15), 3192; https://doi.org/10.3390/polym14153192 - 05 Aug 2022
Cited by 11 | Viewed by 3328
Abstract
Chitosan is a natural anionic polysaccharide with a changeable architecture and an abundance of functional groups; in addition, it can be converted into various shapes and sizes, making it appropriate for a variety of applications. This article examined and summarized current developments in [...] Read more.
Chitosan is a natural anionic polysaccharide with a changeable architecture and an abundance of functional groups; in addition, it can be converted into various shapes and sizes, making it appropriate for a variety of applications. This article examined and summarized current developments in chitosan-based materials, with a focus on the modification of chitosan, and presented an abundance of information about the fabrication and use of chitosan-derived products in periodontal regeneration. Numerous preparation and modification techniques for enhancing chitosan performance, as well as the uses of chitosan and its metabolites, were reviewed critically and discussed in depth in this study. Chitosan-based products may be formed into different shapes and sizes, considering fibers, nanostructures, gels, membranes, and hydrogels. Various drug-loaded chitosan devices were discussed regarding periodontal regeneration. Full article
(This article belongs to the Special Issue Biopolymer-Based Biomimetic Scaffolds)
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