REVIEW article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1670649
This article is part of the Research TopicMesenchymal Stem Cells and Derived Extracellular Vesicles as Next-Generation Biological Drugs for Tissue RegenerationView all 6 articles
Mesenchymal Stromal Cell-Laden Hydrogels in Tissue Regeneration: Insights from Preclinical and Clinical Research
Provisionally accepted
Silvia Barbon1*
Senthilkumar Rajendran2
Antara Banerjee3
Pier Paolo Parnigotto2
Raffaele De Caro1
Veronica Macchi1
Andrea Porzionato1- 1Universita degli Studi di Padova, Padua, Italy
- 2Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling-TES Onlus, Padova, Italy
- 3Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
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Hydrogel-based delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of mesenchymal stromal cells (MSCs) in regenerative medicine. These biomimetic platforms provide a three-dimensional microenvironment that recapitulates key features of native extracellular matrix, supporting MSC viability, retention, and function upon transplantation. Beyond acting as passive carriers, hydrogels can be engineered with tunable biochemical and mechanical properties to modulate MSC behavior, including their differentiation potential, immunomodulatory activity, and paracrine signaling. Recent advances include the development of “smart” hydrogels responsive to physiological stimuli, enabling controlled release of encapsulated cells or bioactive molecules in response to local cues. Preclinical studies have demonstrated enhanced tissue repair in diverse pathological contexts, including musculoskeletal, cardiovascular, gastrointestinal, dermal, and neural injuries. Importantly, translation to clinical settings is being facilitated by the use of xeno-free, good manufacturing practices (GMP)-compliant components such as platelet derivatives and synthetic polymers. Selected early-phase clinical trials support the feasibility, safety, and therapeutic potential of MSC-laden hydrogels, although further studies are required to optimize delivery parameters and regulatory compliance. This review summarizes current progress in hydrogel-MSC systems across application areas, emphasizing design principles, preclinical outcomes, and translational challenges, with the aim of guiding future developments in stem cell-based tissue regeneration.
Keywords: Mesenchymal Stromal Cells, Hydrogels, Tissue Regeneration, Preclinical Research, clinical trials
Received: 21 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Barbon, Rajendran, Banerjee, Parnigotto, De Caro, Macchi and Porzionato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Silvia Barbon, Universita degli Studi di Padova, Padua, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.