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Biomolecules
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Biomolecules and Biomaterials for Tissue Engineering
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Biomolecules and Biomaterials for Tissue Engineering

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological and Bio- Materials".

Deadline for manuscript submissions: closed (15 May 2024) | Viewed by 13897

Special Issue Editor

Prof. Dr. Shinji Sakai

E-Mail Website
Guest Editor
Division of Chemical Engineering, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan
Interests: tissue engineering; regenerative medicine; bioprinting; enzymatic hydrogelation; polysaccharide; hydrogel; drug delivery; cancer model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is with great delight that I present this Special Issue: "Biomolecules and Biomaterials for Tissue Engineering". Tracing back to its roots in the 1990s, tissue engineering has had a transformative trajectory in fields such as regenerative medicine, drug testing, and disease modeling. At the heart of this evolution are biomolecules and biomaterials, intricate components that steer cellular behavior and subsequently enable the fabrication of functional, biomimetic tissues.

This Special Issue underscores the crucial need for a more profound understanding of biomolecules and biomaterials and their diverse roles within tissue engineering. Our focus encompasses the development of novel biomolecules and biomaterials; their applications, including bioprinting; and the innovative strategies involved in their modification. These key topics will be complemented by studies featuring cutting-edge tools and techniques facilitating such progress.

Through this exploration, our Special Issue aims to offer deep insights into the significance of biomolecules and biomaterials, highlighting their role as critical catalysts driving progress in tissue engineering. We warmly invite your valuable contributions—original research or reviews—that will enrich this vital discourse.

Prof. Dr. Shinji Sakai
Guest Editor

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. Biomolecules is an international peer-reviewed open access monthly 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

  • tissue engineering
  • bioactive molecules
  • cellular function
  • proliferation

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Related Special Issue

Published Papers (7 papers)

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Research

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25 pages, 32892 KiB  
Article
Advances in the Toxicity Assessment of Silver Nanoparticles Derived from a Sphagnum fallax Extract for Monolayers and Spheroids
by Liliya Iskuzhina, Svetlana Batasheva, Marina Kryuchkova, Artem Rozhin, Mariya Zolotykh, Rimma Mingaleeva, Farida Akhatova, Anna Stavitskaya, Kirill Cherednichenko and Elvira Rozhina
Biomolecules 2024, 14(6), 611; https://doi.org/10.3390/biom14060611 - 22 May 2024
Viewed by 1328
Abstract
The production of nanomaterials through environmentally friendly methods is a top priority in the sustainable development of nanotechnology. This paper presents data on the synthesis of silver nanoparticles using an aqueous extract of Sphagnum fallax moss at room temperature. The morphology, stability, and [...] Read more.
The production of nanomaterials through environmentally friendly methods is a top priority in the sustainable development of nanotechnology. This paper presents data on the synthesis of silver nanoparticles using an aqueous extract of Sphagnum fallax moss at room temperature. The morphology, stability, and size of the nanoparticles were analyzed using various techniques, including transmission electron microscopy, Doppler laser velocimetry, and UV-vis spectroscopy. In addition, Fourier transform infrared spectroscopy was used to analyze the presence of moss metabolites on the surface of nanomaterials. The effects of different concentrations of citrate-stabilized and moss extract-stabilized silver nanoparticles on cell viability, necrosis induction, and cell impedance were compared. The internalization of silver nanoparticles into both monolayers and three-dimensional cells spheroids was evaluated using dark-field microscopy and hyperspectral imaging. An eco-friendly method for the synthesis of silver nanoparticles at room temperature is proposed, which makes it possible to obtain spherical nanoparticles of 20–30 nm in size with high bioavailability and that have potential applications in various areas of human life. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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12 pages, 4939 KiB  
Article
Transduction and Genome Editing of the Heart with Adeno-Associated Viral Vectors Loaded onto Electrospun Polydioxanone Nonwoven Fabrics
by Kotoko Furuno, Keiichiro Suzuki and Shinji Sakai
Biomolecules 2024, 14(4), 506; https://doi.org/10.3390/biom14040506 - 22 Apr 2024
Cited by 1 | Viewed by 1644
Abstract
In this study, we introduce electrospun polydioxanone (PDO) nonwoven fabrics as a platform for the delivery of adeno-associated virus (AAV) vectors for transduction and genome editing by adhering them to organ surfaces, including the heart. AAV vectors were loaded onto the PDO fabrics [...] Read more.
In this study, we introduce electrospun polydioxanone (PDO) nonwoven fabrics as a platform for the delivery of adeno-associated virus (AAV) vectors for transduction and genome editing by adhering them to organ surfaces, including the heart. AAV vectors were loaded onto the PDO fabrics by soaking the fabrics in a solution containing AAV vectors. In vitro, the amount of AAV vectors loaded onto the fabrics could be adjusted by changing their concentration in the solution, and the number of cells expressing the green fluorescent protein (GFP) encoded by the AAV vectors increased in correlation with the increasing amount of loaded AAV vectors. In vivo, both transduction and genome editing resulted in the observation of GFP expression around AAV vector-loaded PDO fabrics attached to the surfaces of mouse hearts, indicating effective transduction and expression at the target site. These results demonstrate the great potential of electrospun PDO nonwoven fabrics carrying therapeutic AAV vectors for gene therapy. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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22 pages, 13872 KiB  
Article
Novel Organic–Inorganic Nanocomposite Hybrids Based on Bioactive Glass Nanoparticles and Their Enhanced Osteoinductive Properties
by Nicolás Cohn, Henrik Bradtmüller, Edgar Zanotto, Alfredo von Marttens and Cristian Covarrubias
Biomolecules 2024, 14(4), 482; https://doi.org/10.3390/biom14040482 - 16 Apr 2024
Cited by 1 | Viewed by 2034
Abstract
Inorganic–organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first [...] Read more.
Inorganic–organic hybrid biomaterials have been proposed for bone tissue repair, with improved mechanical flexibility compared with scaffolds fabricated from bioceramics. However, obtaining hybrids with osteoinductive properties equivalent to those of bioceramics is still a challenge. In this work, we present for the first time the synthesis of a class II hybrid modified with bioactive glass nanoparticles (nBGs) with osteoinductive properties. The nanocomposite hybrids were produced by incorporating nBGs in situ into a polytetrahydrofuran (PTHF) and silica (SiO2) hybrid synthesis mixture using a combined sol–gel and cationic polymerization method. nBGs ~80 nm in size were synthesized using the sol–gel technique. The structure, composition, morphology, and mechanical properties of the resulting materials were characterized using ATR-FTIR, 29Si MAS NMR, SEM-EDX, AFM, TGA, DSC, mechanical, and DMA testing. The in vitro bioactivity and degradability of the hybrids were assessed in simulated body fluid (SBF) and PBS, respectively. Cytocompatibility with mesenchymal stem cells was assessed using MTS and cell adhesion assays. Osteogenic differentiation was determined using the alkaline phosphatase activity (ALP), as well as the gene expression of Runx2 and Osterix markers. Hybrids loaded with 5, 10, and 15% of nBGs retained the mechanical flexibility of the PTHF–SiO2 matrix and improved its ability to promote the formation of bone-like apatite in SBF. The nBGs did not impair cell viability, increased the ALP activity, and upregulated the expression of Runx2 and Osterix. These results demonstrate that nBGs are an effective osteoinductive nanoadditive for the production of class II hybrid materials with enhanced properties for bone tissue regeneration. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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29 pages, 21589 KiB  
Article
GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways
by Fei Tan, Xuran Li, Xiao Li, Maoxiang Xu, Khawar Ali Shahzad and Lei Hou
Biomolecules 2024, 14(1), 95; https://doi.org/10.3390/biom14010095 - 11 Jan 2024
Cited by 3 | Viewed by 3264
Abstract
Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair [...] Read more.
Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs. Various material characterization methods (e.g., 1H NMR spectroscopy, FT-IR, EIS, and SEM), experimental models (e.g., murine cochlear organoid and aminoglycoside-induced ototoxic HEI-OC1 cellular model), and biological analyses (e.g., confocal laser scanning microscopy, real time qPCR, flow cytometry, and bioinformatic sequencing) were used. The results demonstrated decent material properties of the hydrogel, such as mechanical (e.g., high tensile stress and Young’s modulus), electrochemical (e.g., low impedance and high conductivity), biocompatibility (e.g., satisfactory cochlear cell interaction and free of systemic toxicity), and biosafety (e.g., minimal hemolysis and cell death) features. In addition, the CDR medicinal cocktail sustainably released by the hydrogel not only promoted the expansion of the cochlear stem cells but also boosted the trans-differentiation from cochlear supporting cells into hair cells. Furthermore, hydrogel-based drug delivery protected the hair cells from oxidative stress and various forms of programmed cell death (e.g., apoptosis and ferroptosis). Finally, using large-scale sequencing, we enriched a complex network of signaling pathways that are potentially downstream to various metabolic processes and abundant metabolites. In conclusion, we present a conductive hydrogel-based local delivery of bifunctional drug cocktails, thereby serving as a potential solution to intracochlear therapy of bimodal auditory rehabilitation and diseases beyond. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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21 pages, 5968 KiB  
Article
Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing
by Sachin B. Baravkar, Yan Lu, Abdul-Razak Masoud, Qi Zhao, Jibao He and Song Hong
Biomolecules 2024, 14(1), 94; https://doi.org/10.3390/biom14010094 - 11 Jan 2024
Cited by 2 | Viewed by 1835
Abstract
Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated [...] Read more.
Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Of them, 13 conjugates formed hydrogels at low concentrations (≥0.25% w/v), but C8 acid-ILD-NH2 showed the best hydrogelation and was investigated further. Scanning electron microscopy revealed that C8 acid-ILD-NH2 formed fibrous network structures and rapidly formed hydrogels that were stable in phosphate-buffered saline (pH 2–8, 37 °C), a typical pathophysiological condition. Injection and rheological studies revealed that the hydrogels manifested important wound treatment properties, including injectability, shear thinning, rapid re-gelation, and wound-compatible mechanics (e.g., moduli G″ and G′, ~0.5–15 kPa). The C8 acid-ILD-NH2(2) hydrogel markedly accelerated the healing of third-degree burn wounds on C57BL/6J mice. Taken together, our findings demonstrated the potential of the Cn fatty acid–AA1–AA2–D molecular template to form hydrogels capable of promoting the wound healing of third-degree burns. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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15 pages, 2599 KiB  
Article
Improved Physiochemical Properties of Chitosan@PCL Nerve Conduits by Natural Molecule Crosslinking
by Marta Bianchini, Ciro Zinno, Silvestro Micera and Eugenio Redolfi Riva
Biomolecules 2023, 13(12), 1712; https://doi.org/10.3390/biom13121712 - 27 Nov 2023
Cited by 3 | Viewed by 1461
Abstract
Nerve conduits may represent a valuable alternative to autograft for the regeneration of long-gap damages. However, no NCs have currently reached market approval for the regeneration of limiting gap lesions, which still represents the very bottleneck of this technology. In recent years, a [...] Read more.
Nerve conduits may represent a valuable alternative to autograft for the regeneration of long-gap damages. However, no NCs have currently reached market approval for the regeneration of limiting gap lesions, which still represents the very bottleneck of this technology. In recent years, a strong effort has been made to envision an engineered graft to tackle this issue. In our recent work, we presented a novel design of porous/3D-printed chitosan/poly-ε-caprolactone conduits, coupling freeze drying and additive manufacturing technologies to yield conduits with good structural properties. In this work, we studied genipin crosslinking as strategy to improve the physiochemical properties of our conduit. Genipin is a natural molecule with very low toxicity that has been used to crosslink chitosan porous matrix by binding the primary amino group of chitosan chains. Our characterization evidenced a stabilizing effect of genipin crosslinking towards the chitosan matrix, with reported modified porosity and ameliorated mechanical properties. Given the reported results, this method has the potential to improve the performance of our conduits for the regeneration of long-gap nerve injuries. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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Review

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39 pages, 2267 KiB  
Review
Recent Advances in Hydrogel-Based 3D Bioprinting and Its Potential Application in the Treatment of Congenital Heart Disease
by Tasneem Salih, Massimo Caputo and Mohamed T. Ghorbel
Biomolecules 2024, 14(7), 861; https://doi.org/10.3390/biom14070861 - 18 Jul 2024
Viewed by 1436
Abstract
Congenital heart disease (CHD) is the most common birth defect, requiring invasive surgery often before a child’s first birthday. Current materials used during CHD surgery lack the ability to grow, remodel, and regenerate. To solve those limitations, 3D bioprinting is an emerging tool [...] Read more.
Congenital heart disease (CHD) is the most common birth defect, requiring invasive surgery often before a child’s first birthday. Current materials used during CHD surgery lack the ability to grow, remodel, and regenerate. To solve those limitations, 3D bioprinting is an emerging tool with the capability to create tailored constructs based on patients’ own imaging data with the ability to grow and remodel once implanted in children with CHD. It has the potential to integrate multiple bioinks with several cell types and biomolecules within 3D-bioprinted constructs that exhibit good structural fidelity, stability, and mechanical integrity. This review gives an overview of CHD and recent advancements in 3D bioprinting technologies with potential use in the treatment of CHD. Moreover, the selection of appropriate biomaterials based on their chemical, physical, and biological properties that are further manipulated to suit their application are also discussed. An introduction to bioink formulations composed of various biomaterials with emphasis on multiple cell types and biomolecules is briefly overviewed. Vasculogenesis and angiogenesis of prefabricated 3D-bioprinted structures and novel 4D printing technology are also summarized. Finally, we discuss several restrictions and our perspective on future directions in 3D bioprinting technologies in the treatment of CHD. Full article
(This article belongs to the Special Issue Biomolecules and Biomaterials for Tissue Engineering)
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