Advancements in Pro-Regenerative Hydrogel Scaffolds for Tissue Engineering and Regenerative Medicine

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 3495

Special Issue Editors


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Guest Editor
Innovation Center of Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
Interests: biomaterials; polymeric drug delivery systems; tissue engineering; scaffolds; wound healing; controlled and targeted drug delivery; multi-target drug delivery systems
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Guest Editor
1. Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
2. University Clinical Center of Serbia, Clinic of Dermatology and Venerology, 11000 Belgrade, Serbia
Interests: wound healing; autoimmune blistering disorders; biologics in dermatology; wound tissue regeneration

Special Issue Information

Dear Colleagues,

We are delighted to introduce the Special Issue of Pharmaceutics, entitled “Advancements in Pro-Regenerative Hydrogel Scaffolds for Tissue Engineering and Regenerative Medicine”, which focuses on the latest advancements in pro-regenerative hydrogel scaffold engineering for regenerative medicine. The developments in the fields of tissue engineering and regenerative medicine are fundamentally inspired by the goal of addressing a broad spectrum of clinical challenges, especially those related to replicating environments of native tissue by a single approach. One of the revolutionary strategies in the field of tissue engineering/regeneration is the use of 3D pro-regenerative hydrogel scaffolds with superior biomimicry and bioactivity.

The pro-regenerative hydrogel scaffolds are capable of adapting to the dynamic tissue regeneration/engineering processes, providing a biomimetic environment that supports cellular processes and interactions as well as the formation of health tissue in three dimensions through a replicated extracellular matrix (ECM). Additional regenerative properties of these pro-regenerative hydrogel scaffolds could be engineered by loading them with different bioactive agents, including cells, growth factors, antimicrobial and anti-inflammatory agents, or multiple bioactive agents that promote tissue regeneration processes. Various synthetic monomers and natural polymers possess significant biophysiological potential for the design of pro-regenerative hydrogel scaffolds for tissue engineering/regeneration, such as 2-hydroxyethyl (meth)acrylate, gelatin, alginate, chitosan, hyaluronic acid, and collagen, but the engineering of pro-regenerative hydrogel scaffolds that simultaneously provide biophysiological support for cellular processes and precisely mimic the anatomical shapes and microstructures crucial for effective tissue regeneration presents further challenges in both the design and synthesis of these hydrogel scaffolds.

The goal of this Special Issue is to highlight advancements in the area of pro-regenerative hydrogel scaffolding biomaterials for applications in tissue engineering and regenerative medicine. Of special interest are papers that present innovative strategies for the engineering of pro-regenerative hydrogel scaffolds for bone regeneration, wound healing, cartilage, and nerve reparation, as well as papers that cover the engineering of 3D tumor tissue for clinical trials of novel active agents. We believe that the topic of this Special Issue will stimulate groundbreaking research and attract significant interest from a wide audience in the field of pro-regenerative hydrogel scaffolds for tissue engineering and regenerative medicine. We look forward to receiving your contributions.

Dr. Marija M. Babić Radić
Dr. Dubravka P. Živanović
Guest Editors

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Keywords

  • pro-regenerative scaffolds for tissue engineering
  • ECM-like hydrogel substitutes
  • scaffolds for wound healing
  • scaffolds for bone and cartilage regeneration
  • scaffolds for nerve reparation
  • bioactive 3D scaffolds
  • scaffolds for engineering of 3D tumor tissue
  • multi-biofunctional scaffolds for tissue regeneration

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Published Papers (2 papers)

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Research

18 pages, 4508 KiB  
Article
Design of the Multi-Bioactive Graphene-Oxide/Gelatin/Alginate Scaffolds as Dual ECM-Mimetic and Specific Wound Healing Phase-Target Therapeutic Concept for Advanced Wound Healing
by Marko Demenj, Martina Žabčić, Marija Vukomanović, Tatjana Ilić-Tomić, Dušan Milivojević, Simonida Tomić, Dubravka Živanović and Marija M. Babić Radić
Pharmaceutics 2025, 17(1), 89; https://doi.org/10.3390/pharmaceutics17010089 - 12 Jan 2025
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Abstract
Objectives: To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three [...] Read more.
Objectives: To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. Methods: The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using Caenorhabditis elegans assay. Results: The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93–96%) and mechanical strength (1.10–2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the Caenorhabditis elegans throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds’ significant potential for simultaneous release. Conclusion: The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process. Full article
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15 pages, 7204 KiB  
Article
The Application of Resolvin D1-Loaded Gelatin Methacrylate in a Rat Periodontitis Model
by Zhe Xing, Jing Liu, Jiazheng Cai, Xiaofeng Jiang, Jingwen Liang, Masahito Fujio, Elin Hadler-Olsen, Jing Wang, Alpdogan Kantarci and Ying Xue
Pharmaceutics 2025, 17(1), 16; https://doi.org/10.3390/pharmaceutics17010016 - 25 Dec 2024
Viewed by 1034
Abstract
Objective: To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. Methods: An RvD1 complexed with GelMA was prepared, and its release [...] Read more.
Objective: To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. Methods: An RvD1 complexed with GelMA was prepared, and its release kinetics and compatibility with PDLCs were assessed. Rats with induced periodontitis were treated weekly with topical applications of vehicle, GelMA, RvD1, or RvD1 complexed with GelMA for four weeks. Periodontal inflammation and tissue regeneration were evaluated using quantitative PCR (qPCR) and histochemical staining, while alveolar bone repair and regeneration were analyzed through micro-CT. Results: The RvD1 complexed with GelMA effectively released RvD1 and enhanced the proliferation and viability of PDLCs. Compared to RvD1 alone, treatment with RvD1 complexed with GelMA significantly reduced inflammatory cell infiltration, TNF-α and RANKL expression, and osteoclast formation in periodontal tissues. Additionally, it promoted the expression of specific anti-inflammatory and regenerative markers. Micro-CT analysis confirmed significant new bone formation in the RvD1 complexed with GelMA-treated group. Conclusions: RvD1 complexed with GelMA provides sustained drug release and biocompatibility, effectively resolves periodontal inflammation, and promotes tissue regeneration in periodontitis. Full article
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