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Advanced Functional Biomaterials in Regenerative Medicine
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Advanced Functional Biomaterials in Regenerative Medicine

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Biomaterials for Tissue Engineering and Regenerative Medicine".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 23038

Special Issue Editors

Prof. Dr. Andreas K. Nüssler

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Guest Editor
Siegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, Germany
Interests: bone metabolic diseases; bone biology; stem cell; bone tissue; osteogenic differentiation
Special Issues, Collections and Topics in MDPI journals
Dr. Sabrina Ehnert

E-Mail Website
Guest Editor
Siegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, Germany
Interests: cell culture; gene expression; medicinal and pharmaceutical chemistry; antioxidants; general surgery; reactive oxygen species; pharmacodynamics; traumatology; bone; bone metabolism; liver; diabetes; toxicology; glutathione; osteoblasts; osteoclasts; mechanotransduction; hepatocytes
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ashok Kumar

E-Mail Website
Guest Editor
Department of Biological Sciences and Bioengineering, Centre for Environmental Science and Engineering, Centre for Nanosciences, The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India
Interests: tissue engineering; biomaterials; regenerative medicine; cryogels; environmental biotechnology

Special Issue Information

Dear Colleagues,

Despite all advancements in implant design and surgical techniques, up to 10% of all broken bones worldwide still do not heal properly. The costs associated with this are enormous, weighing equally on social security spending and patient wellbeing. Although significant advances have been achieved in the last few decades in the development of new materials to overcome bone and wound healing disorders, there remains a high unmet medical need to bridge the gap in unhealed fractures. We are aiming to gather new ideas here to develop new biomaterials that can promote bone and tissue regeneration. This can be achieved through, e.g., functional adaptation of biomaterial design; improved adjustment of mechanical properties; changes in surface structures, internal porosity, or the material property itself, active drug, synthetic mRNA, or exosome release from the implant, etc., as they can directly affect the surrounding cell response (such as cell adhesion, proliferation, differentiation, etc.). Other topics include new biomaterials to improve clinical diagnosis of non-unions, treatment strategies, and early identification of risk patients. We welcome contributions on the following topics (articles, reviews, opinions, and observations):

  • New biomaterials in medical technology
  • Bionanomaterials
  • Biomaterial applications in the field of implants
  • Biomaterial interaction and cells
  • (Bio)material applications in the non-implant area
  • Biocompatibility and biofunctionality, in vitro and in vivo tests
  • Functional Biomaterials
  • Biomaterials as drug delivery agents

Prof. Dr. Andreas K. Nüssler
Dr. Sabrina Ehnert
Prof. Dr. Ashok Kumar
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. Journal of Functional Biomaterials 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

  • new biomaterials in medical technology
  • bionanomaterials
  • biomaterial applications in the field of implants
  • biomaterial interaction and cells
  • (bio)material applications in the non-implant area
  • biocompatibility and biofunctionality
  • in vitro and in vivo tests
  • functional biomaterials
  • biomaterials as drug delivery agents

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Published Papers (5 papers)

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Research

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24 pages, 30692 KiB  
Article
Sacrificing Alginate in Decellularized Extracellular Matrix Scaffolds for Implantable Artificial Livers
by Chanh-Trung Nguyen, Van Phu Le, Thi Huong Le, Jeong Sook Kim, Sung Hoon Back and Kyo-in Koo
J. Funct. Biomater. 2025, 16(1), 35; https://doi.org/10.3390/jfb16010035 - 19 Jan 2025
Viewed by 1798
Abstract
This research introduced a strategy to fabricate sub-millimeter-diameter artificial liver tissue by extruding a combination of a liver decellularized extracellular matrix (dECM), alginate, endothelial cells, and hepatocytes. Vascularization remains a critical challenge in liver tissue engineering, as replicating the liver’s intricate vascular network [...] Read more.
This research introduced a strategy to fabricate sub-millimeter-diameter artificial liver tissue by extruding a combination of a liver decellularized extracellular matrix (dECM), alginate, endothelial cells, and hepatocytes. Vascularization remains a critical challenge in liver tissue engineering, as replicating the liver’s intricate vascular network is essential for sustaining cellular function and viability. Seven scaffold groups were evaluated, incorporating different cell compositions, scaffold materials, and structural configurations. The hepatocyte and endothelial cell scaffold treated with alginate lyase demonstrated the highest diffusion rate, along with enhanced albumin secretion (2.8 µg/mL) and urea synthesis (220 µg/mL) during the same period by day 10. A dense and interconnected endothelial cell network was observed as early as day 4 in the lyased coculture group. Furthermore, three-week implantation studies in rats showed a stable integration to the host with no adverse effects. This approach offers significant potential for advancing functional liver tissue replacements, combining accelerated diffusion, enhanced albumin secretion, improved urea synthesis, dense vascular network formation, and stable implantation outcomes. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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14 pages, 14183 KiB  
Article
In Vitro and In Vivo Analysis of the Mg-Ca-Zn Biodegradable Alloys
by Bogdan Istrate, Florina-Daniela Cojocaru, Mădălina-Elena Henea, Vera Balan, Eusebiu-Viorel Șindilar, Liliana Verestiuc, Corneliu Munteanu and Carmen Solcan
J. Funct. Biomater. 2024, 15(6), 166; https://doi.org/10.3390/jfb15060166 - 17 Jun 2024
Cited by 4 | Viewed by 1768
Abstract
The objective of this work was to analyze the in vitro and in vivo tests of a novel Mg-based biodegradable alloy—Mg-0.5%Ca—with various amounts of Zn (0.5, 1, 1.5, 2.0, and 3.0 wt.%). In terms of in vitro biocompatibility, MTT and Calcein-AM cell viability [...] Read more.
The objective of this work was to analyze the in vitro and in vivo tests of a novel Mg-based biodegradable alloy—Mg-0.5%Ca—with various amounts of Zn (0.5, 1, 1.5, 2.0, and 3.0 wt.%). In terms of in vitro biocompatibility, MTT and Calcein-AM cell viability assays, performed on the MG-63 cell line through the extract method, revealed that all five alloy extracts are non-cytotoxic at an extraction ratio of 0.025 g alloy per mL of cell culture medium. In the in vivo histological analysis, Mg-0.5Ca-1.5Zn demonstrated exceptional potential for stimulating bone remodeling and showed excellent biocompatibility. It was observed that Mg-0.5Ca-0.5Zn, Mg-0.5Ca-1.5Zn, and Mg-0.5Ca-3Zn displayed good biocompatibility. Furthermore, the histological examination highlighted the differentiation of periosteal cells into chondrocytes and subsequent bone tissue replacement through endochondral ossification. This process highlighted the importance of the initial implant’s integrity and the role of the periosteum. In summary, Mg-0.5Ca-1.5Zn stands out as a promising candidate for bone regeneration and osseointegration, supported by both in vitro and in vivo findings. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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17 pages, 3898 KiB  
Article
Establishing the Callus-Based Isolation of Extracellular Vesicles from Cissus quadrangularis and Elucidating Their Role in Osteogenic Differentiation
by Ritu Gupta, Sneha Gupta, Purva Gupta, Andreas K. Nüssler and Ashok Kumar
J. Funct. Biomater. 2023, 14(11), 540; https://doi.org/10.3390/jfb14110540 - 2 Nov 2023
Cited by 10 | Viewed by 3813
Abstract
Extracellular vesicles (EVs) are nano-sized vehicles secreted by all live cells to establish communication with adjacent cells. In recent years, mammalian EVs (MEVs) have been widely investigated for their therapeutic implications in human disease conditions. As the understanding of MEV composition and nature [...] Read more.
Extracellular vesicles (EVs) are nano-sized vehicles secreted by all live cells to establish communication with adjacent cells. In recent years, mammalian EVs (MEVs) have been widely investigated for their therapeutic implications in human disease conditions. As the understanding of MEV composition and nature is advancing, scientists are constantly exploring alternatives for EV production with similar therapeutic potential. Plant-derived exosome-like nanovesicles (PDEVs) may be a better substitute for MEVs because of their widespread sources, cost-effectiveness, and ease of access. Cissus quadrangularis (CQ), known as “bone setter or Hadjod”, is a perennial plant utilized for its osteogenic potential. Its crude powder extract formulations are widely used as tablets and syrups. The present work elucidates the isolation of exosome-like nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from CQ. The physical and biological properties of the exosomes were successfully investigated using different characterization techniques. The therapeutic potential of the CQ exosomes was found to ameliorate the wound scratch injury and oxidative stress conditions in human-derived mesenchymal stem cells (hMSCs) and the pre-osteoblast (MC3T3) cell line. These exosomes also induced the proliferation and differentiation of hMSCs, as observed by alkaline phosphatase activity. These findings may serve as a proof of concept for further investigating the CQ exosomes as a nanocarrier for drug molecules in various therapeutic bone applications. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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Review

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24 pages, 3942 KiB  
Review
Advances in Fabrication Technologies for the Development of Next-Generation Cardiovascular Stents
by Ankita Das, Shreya Mehrotra and Ashok Kumar
J. Funct. Biomater. 2023, 14(11), 544; https://doi.org/10.3390/jfb14110544 - 10 Nov 2023
Cited by 5 | Viewed by 5642
Abstract
Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct, called a stent, inside arteries to restore blood flow. However, due to lack of patient-specific design, the [...] Read more.
Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct, called a stent, inside arteries to restore blood flow. However, due to lack of patient-specific design, the commercial products cannot be used with different vessel anatomies. In this review, we have summarized the drawbacks in existing commercial metal stents which face problems of restenosis and inflammatory responses, owing to the development of neointimal hyperplasia. Further, we have highlighted the fabrication of stents using biodegradable polymers, which can circumvent most of the existing limitations. In this regard, we elaborated on the utilization of new fabrication methodologies based on additive manufacturing such as three-dimensional printing to design patient-specific stents. Finally, we have discussed the functionalization of these stent surfaces with suitable bioactive molecules which can prove to enhance their properties in preventing thrombosis and better healing of injured blood vessel lining. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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35 pages, 13678 KiB  
Review
The Concept of Scaffold-Guided Bone Regeneration for the Treatment of Long Bone Defects: Current Clinical Application and Future Perspective
by Markus Laubach, Frank Hildebrand, Sinduja Suresh, Michael Wagels, Philipp Kobbe, Fabian Gilbert, Ulrich Kneser, Boris M. Holzapfel and Dietmar W. Hutmacher
J. Funct. Biomater. 2023, 14(7), 341; https://doi.org/10.3390/jfb14070341 - 27 Jun 2023
Cited by 67 | Viewed by 8819
Abstract
The treatment of bone defects remains a challenging clinical problem with high reintervention rates, morbidity, and resulting significant healthcare costs. Surgical techniques are constantly evolving, but outcomes can be influenced by several parameters, including the patient’s age, comorbidities, systemic disorders, the anatomical location [...] Read more.
The treatment of bone defects remains a challenging clinical problem with high reintervention rates, morbidity, and resulting significant healthcare costs. Surgical techniques are constantly evolving, but outcomes can be influenced by several parameters, including the patient’s age, comorbidities, systemic disorders, the anatomical location of the defect, and the surgeon’s preference and experience. The most used therapeutic modalities for the regeneration of long bone defects include distraction osteogenesis (bone transport), free vascularized fibular grafts, the Masquelet technique, allograft, and (arthroplasty with) mega-prostheses. Over the past 25 years, three-dimensional (3D) printing, a breakthrough layer-by-layer manufacturing technology that produces final parts directly from 3D model data, has taken off and transformed the treatment of bone defects by enabling personalized therapies with highly porous 3D-printed implants tailored to the patient. Therefore, to reduce the morbidities and complications associated with current treatment regimens, efforts have been made in translational research toward 3D-printed scaffolds to facilitate bone regeneration. Three-dimensional printed scaffolds should not only provide osteoconductive surfaces for cell attachment and subsequent bone formation but also provide physical support and containment of bone graft material during the regeneration process, enhancing bone ingrowth, while simultaneously, orthopaedic implants supply mechanical strength with rigid, stable external and/or internal fixation. In this perspective review, we focus on elaborating on the history of bone defect treatment methods and assessing current treatment approaches as well as recent developments, including existing evidence on the advantages and disadvantages of 3D-printed scaffolds for bone defect regeneration. Furthermore, it is evident that the regulatory framework and organization and financing of evidence-based clinical trials remains very complex, and new challenges for non-biodegradable and biodegradable 3D-printed scaffolds for bone regeneration are emerging that have not yet been sufficiently addressed, such as guideline development for specific surgical indications, clinically feasible design concepts for needed multicentre international preclinical and clinical trials, the current medico-legal status, and reimbursement. These challenges underscore the need for intensive exchange and open and honest debate among leaders in the field. This goal can be addressed in a well-planned and focused stakeholder workshop on the topic of patient-specific 3D-printed scaffolds for long bone defect regeneration, as proposed in this perspective review. Full article
(This article belongs to the Special Issue Advanced Functional Biomaterials in Regenerative Medicine)
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