Advancements in Regenerative Medicine: An Integrated Approach Using Nanotechnology and 3D Culture Platforms

A special issue of Biomimetics (ISSN 2313-7673). This special issue belongs to the section "Development of Biomimetic Methodology".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 5978

Special Issue Editor


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Guest Editor
Department of Systems Biotechnology, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
Interests: modeling and treatment of vascular diseases using stem cells; development of multifunctional biomimetic nanoparticles; development of human blood–brain barrier-on-a-chip; mechanistic relationship of blood–brain barrier disruption and neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Interdisciplinary advancements in tissue engineering and biomedical engineering have integrated various approaches to reconstruct damaged tissues caused by trauma, disease, or genetic disorders. In addition to the conventional regenerative medicine technologies involved in stem cell transplantation, nanotechnologies and 3D cell culture platforms have exhibited their potential to enhance the therapeutic functions of target cells and tissues. These strategies offer the advantage of making biomimetic adjustments to the complex cellular microenvironment to closely resemble that of healthy tissue. The incorporation of such biological, chemical, physical, and mechanical cues enhances the regenerative efficacy by addressing the shortcomings of conventional cell therapies, such as low engraftment and survival rates.

This Special Issue covers the diverse biomimetic nanotechnologies and 3D cell culture platforms that can advance regenerative medicine and stem cell therapy. This Special Issue focuses on a variety of bioactive nanomaterials, such as polymeric or inorganic nanoparticles, as well as exosomes and cell-derived nanovesicles which are emerging alternatives to cell therapies. With regard to 3D cell culture platforms, the scope encompasses traditional domains, such as spheroids and hydrogels, as well as organoids for transplantation. I welcome original articles that present innovative regenerative strategies, as well as reviews and perspectives that elucidate the authors’ valuable insights.

Dr. Jeong-Kee Yoon
Guest Editor

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Keywords

  • regenerative medicine
  • tissue engineering
  • nanotechnology
  • 3D cell culture
  • stem cells
  • exosomes
  • cell therapy

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Published Papers (4 papers)

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Research

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17 pages, 5963 KiB  
Article
Enhanced Bladder Regeneration with Adipose-Derived Stem Cell-Seeded Silk Fibroin Scaffolds: A Comparative Analysis
by Hanan Hendawy, Ahmed Farag, Asmaa Elhaieg, Elsayed Metwllay, Kazumi Shimada, Ahmed Elfadadny and Ryou Tanaka
Biomimetics 2025, 10(2), 93; https://doi.org/10.3390/biomimetics10020093 - 7 Feb 2025
Cited by 1 | Viewed by 847
Abstract
Effective bladder reconstruction remains a significant challenge in urology, particularly for conditions requiring partial or complete bladder replacement. In this study, the efficacy is evaluated of two types of scaffolds, silk fibroin (SF) and adipose-derived stem cells (ADSCs-SF), in promoting bladder regeneration and [...] Read more.
Effective bladder reconstruction remains a significant challenge in urology, particularly for conditions requiring partial or complete bladder replacement. In this study, the efficacy is evaluated of two types of scaffolds, silk fibroin (SF) and adipose-derived stem cells (ADSCs-SF), in promoting bladder regeneration and their associated outcomes. A rat model was used to compare the surgical outcomes and morphological recovery of bladder tissues implanted with SF and ADSCs-SF scaffolds. Post-operative recovery, including voiding ability and complication rates, was assessed. The morphological and histological changes of the regenerated bladder tissue were evaluated at multiple time points (2, 4, 8, and 12 weeks) using gross tissue analysis, histometric assessments, and immunohistochemical staining. Both scaffold types demonstrated successful integration into the bladder wall with no significant differences in body weight or voiding issues. The SF scaffold group exhibited graft shrinkage and a 41.6% incidence of bladder calculus formation. In contrast, the ADSCs-SF scaffold facilitated superior morphological restoration, with bladder tissue progressively adopting a more normal shape and no incidence of bladder calculus. Histological analysis revealed that the ADSCs-SF scaffold significantly promoted the regeneration of a more organized urothelium layer and smooth muscle tissue. It also resulted in higher vessel density and reduced infiltration of inflammatory cells when compared to the SF scaffold alone. Additionally, the ADSCs-SF group exhibited enhanced expression of key markers, including uroplakin III, a urothelial marker, and α-SMA, a smooth muscle cell marker. These findings suggest that the ADSCs-SF scaffold not only supports the structural integrity of the bladder but also improves tissue regeneration and reduces adverse inflammatory responses, offering a promising approach for bladder repair and reconstruction. Full article
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15 pages, 2958 KiB  
Article
Facile One-Pot Preparation of Self-Assembled Hyaluronate/Doxorubicin Nanoaggregates for Cancer Therapy
by Yong Geun Lim, Hyung Geun Park and Kyeongsoon Park
Biomimetics 2025, 10(2), 91; https://doi.org/10.3390/biomimetics10020091 - 6 Feb 2025
Viewed by 759
Abstract
Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming [...] Read more.
Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming purification, and the use of crosslinkers or surfactants, which can cause undesired toxicities. To resolve these issues, we developed a facile one-pot method to prepare self-assembled sodium hyaluronate/doxorubicin (HA/DOX) nanoaggregates by mixing HA and DOX. The self-assembled HA/DOX nanoaggregates were formed via cation–π interactions between the aromatic moiety of DOX and Na+ ions in HA as well as electrostatic interactions between HA and DOX. The optimized HA/DOX nanoaggregates with a [DOX]/[HA] molar ratio of 5 had an average particle size of approximately 250 nm and a sphere-like shape. In vitro studies revealed that HA/DOX nanoaggregates effectively targeted CD44-overexpressing cancer cells, selectively delivering DOX into the cell nuclei more efficiently than free DOX and resulting in enhanced cytotoxic effects. Annexin V and transferase dUTP nick-end labeling assays confirmed that HA/DOX nanoaggregates induced apoptosis via DNA fragmentation more effectively than free DOX. Full article
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Review

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20 pages, 4995 KiB  
Review
The Potential of Mesenchymal Stem Cell-Derived Exosomes to Treat Diabetes Mellitus
by Ju-El Kim, Jong-Won Lee, Gi Doo Cha and Jeong-Kee Yoon
Biomimetics 2025, 10(1), 49; https://doi.org/10.3390/biomimetics10010049 - 14 Jan 2025
Cited by 1 | Viewed by 1627
Abstract
Diabetes mellitus (DM) is a fatal metabolic disease characterized by persistent hyperglycemia. In recent studies, mesenchymal stem cell (MSC)-derived exosomes, which are being investigated clinically as a cell-free therapy for various diseases, have gained attention due to their biomimetic properties that closely resemble [...] Read more.
Diabetes mellitus (DM) is a fatal metabolic disease characterized by persistent hyperglycemia. In recent studies, mesenchymal stem cell (MSC)-derived exosomes, which are being investigated clinically as a cell-free therapy for various diseases, have gained attention due to their biomimetic properties that closely resemble natural cellular communication systems. These MSC-derived exosomes inherit the regenerative and protective effects from MSCs, inducing pancreatic β-cell proliferation and inhibiting apoptosis, as well as ameliorating insulin resistance by suppressing the release of various inflammatory cytokines. Consequently, MSC-derived exosomes have attracted attention as a novel treatment for DM as an alternative to stem cell therapy. In this review, we will introduce the potential of MSC-derived exosomes for the treatment of DM by discussing the studies that have used MSC-derived exosomes to treat DM, which have shown therapeutic effects in both type 1 and type 2 DM. Full article
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16 pages, 1179 KiB  
Review
The Role of the Pancreatic Extracellular Matrix as a Tissue Engineering Support for the Bioartificial Pancreas
by Thamires Santos da Silva, Leandro Norberto da Silva-Júnior, Bianca de Oliveira Horvath-Pereira, Maria Carolina Miglino Valbão, Matheus Henrique Herminio Garcia, Juliana Barbosa Lopes, Carlos Henrique Bertoni Reis, Rodrigo da Silva Nunes Barreto, Daniela Vieira Buchaim, Rogerio Leone Buchaim and Maria Angelica Miglino
Biomimetics 2024, 9(10), 598; https://doi.org/10.3390/biomimetics9100598 - 2 Oct 2024
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Abstract
Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate [...] Read more.
Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate vascularization. The main limitations to clinical islet transplantation are the scarcity of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. Despite extensive research, T1DM remains a major global health issue. In 2015, diabetes affected approximately 415 million people, with projected expenditures of USD 1.7 trillion by 2030. Pancreas transplantation faces challenges due to limited organ availability and complex vascularization. T1DM is caused by the autoimmune destruction of insulin-producing pancreatic cells. Advances in biomaterials, particularly the extracellular matrix (ECM), show promise in tissue reconstruction and transplantation, offering structural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas’s intricate architecture and maintaining cell viability and functionality. Emerging technologies, such as 3D printing and advanced biomaterials, have shown potential in constructing bioartificial organs. ECM components, including collagens and glycoproteins, play essential roles in cell adhesion, migration, and differentiation. Clinical applications focus on developing functional scaffolds for transplantation, with ongoing research addressing immunological responses and long-term efficacy. Pancreatic bioengineering represents a promising avenue for T1DM treatment, requiring further research to ensure successful implementation. Full article
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