Translation of Regenerative Medicines: Advances in Pharmacological Modulation, Manufacturing, Potency, and Delivery

Background:Regenerative medicines comprise a diverse group of advanced therapies whose regulatory classifications differ across major jurisdictions. In the United States, the FDA, under the 21st Century Cures Act (2016), defines regenerative medicine therapies to include cell therapies, therapeutic tissue-engineering products, human cell and tissue products, and combination products, with certain gene therapies also potentially meeting this definition and eligible products able to receive the Regenerative Medicine Advanced Therapy (RMAT) designation. In the European Union, related products are regulated within the Advanced Therapy Medicinal Product (ATMP) framework under Regulation (EC) No 1394/2007, overseen by the European Medicines Agency (EMA, formerly EMEA) and its Committee for Advanced Therapies, with ATMPs comprising gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products, as well as combined ATMPs.While these regulatory definitions and classifications delineate product categories, they do not by themselves explain how therapeutic activity is generated, maintained, or altered throughout development. Regenerative medicines are increasingly understood as biologically responsive interventions rather than fixed products. Their therapeutic activity is not determined at a single point but can be shaped across the development pathway, where biochemical and pharmacological influences may alter phenotype, secretory and immunomodulatory activity, survival, tissue interactions, and ultimately therapeutic performance.A central translational challenge is that the factors shaping this activity are often studied in isolation. A functional gain demonstrated at one stage may not be confirmed downstream; the biological consequences of processing decisions may go unmeasured; potency readouts may not adequately reflect the underlying mechanism of action; and therapeutic function may be altered or lost before a product reaches the target tissue. Considered separately, these steps can obscure an important principle: the biological function of a regenerative medicine can be shaped across multiple stages of development rather than at any single point.This Research Topic therefore adopts an integrative, function-centred perspective on regenerative medicine, examining how pharmacological and bioactive modulation can be connected across this pathway to preserve biologically relevant function and strengthen translational potential. In doing so, it complements regulatory classification with a mechanistic, activity-based perspective on how therapeutic function is shaped across development. The specific stages through which these relationships can be investigated are set out in the Key Themes below.Central QuestionHow can pharmacological and bioactive modulation be integrated with manufacturing, potency assessment, preservation, and delivery so that regenerative medicines retain predictable biological function from experimental development through therapeutic administration?Key ThemesContributions may address one or more stages of this pathway, but all manuscripts should retain a clear pharmacological, mechanistic, or experimentally validated connection to tissue regeneration or repair.• Pharmacological priming and functional modulation of regenerative therapies – including cytokines, growth factors, small molecules, metabolic or epigenetic modulation, inflammatory licensing, and other bioactive conditioning strategies. • Manufacturing as a determinant of pharmacological and regenerative function – examining how culture conditions, expansion, process changes, and integration of priming strategies influence cell state, product quality, and therapeutic function. • Mechanism of action, critical quality attributes, and potency – linking molecular and cellular mechanisms with measurable product attributes, functional assays, and regenerative efficacy. • Formulation, cryopreservation, and post-preservation functional recovery – focusing on preservation of biologically relevant phenotypes, potency, and therapeutic function. • Biomaterials and drug-delivery strategies for regenerative pharmacology – including controlled or targeted delivery of bioactive agents, cells, extracellular vesicles, and other regenerative products. • Cell-free and bioactive regenerative therapeutics – including extracellular vesicles, secretomes, bioactive proteins and peptides, and pharmacologically modified cell-derived products. • Regenerative microenvironments and recipient-tissue pharmacology – addressing inflammation, immune regulation, fibrosis, senescence, • metabolism, angiogenesis, and therapeutic product–tissue interactions.Translational validation of pharmacologically modified regenerative medicines – including relevant in vitro, ex vivo, and in vivo models, persistence of functional states, dosing, safety, biodistribution, and functional comparability.ScopeThe Research Topic aims to bridge regenerative pharmacology with manufacturing, potency, preservation, and delivery without becoming a general bioprocessing or CMC collection.We particularly welcome fundamental, experimental, preclinical, and translational studies addressing pharmacologically or biologically modulated regenerative therapies, mechanism-linked potency and functional assays, biologically meaningful manufacturing interventions, regenerative biomaterials and delivery technologies, cell-derived and cell-free therapeutics, and interactions between therapeutic products and regenerative microenvironments.Studies focused solely on process engineering or scale-up, equipment or facility design, generic GMP/CMC considerations, technical cryopreservation without functional assessment, regulatory or economic analysis without a pharmacological or experimental basis, or computational/database studies without appropriate experimental validation would generally fall outside the intended scope.The Research Topic welcomes Original Research, Reviews and Mini Reviews, Perspectives and Opinions, Methods, and Hypothesis and Theory articles.Cross-disciplinary submissions connecting pharmacology with regenerative medicine, cell biology, tissue engineering, biomaterials, drug delivery, and translational science are particularly encouraged. Topic editors: Ali Shokoohmand, Hamid Bidkhori, Guido Moll Source: https://www.frontiersin.org/research-topics/85229/translation-of-regenerative-medicines-advances-in-pharmacological-modulation-manufacturing-potency-and-delivery