Bioengineering Strategies to Overcome Translational Barriers in Cell and Gene Therapy for Tissue Repair

Stem cell and gene-based therapies hold significant promise for tissue repair and regenerative medicine, yet their clinical translation remains limited by major biological barriers. Poor cell retention following transplantation, limited survival within hostile inflammatory microenvironments, insufficient engraftment, and inadequate paracrine signalling continue to hamper therapeutic outcomes. These challenges are not confined to a single organ system; they are observed across the heart, skeletal muscle, nervous system, skin, liver, kidneys, lungs, and musculoskeletal tissues. Despite decades of preclinical progress, bridging the gap between experimental promise and meaningful clinical impact remains one of the central challenges in the field. Overcoming these barriers requires innovative bioengineering and biotechnology approaches capable of modifying, enhancing, or protecting therapeutic cells and genetic payloads before and after delivery to injured tissues.This Research Topic aims to bring together cutting-edge research on the bioengineering strategies best positioned to overcome the translational barriers facing cell and gene therapies. By uniting investigators working across complementary methodologies, from biophysical stimulation to biomaterial design to genetic engineering, the collection seeks to define the state of the art and identify the most promising pathways towards clinical application. Among the approaches highlighted, photobiomodulation, encompassing light-emitting diode (LED) and low-level laser therapy (LLLT), is featured as a promising bioengineering tool for optimising stem cells, progenitor cells, extracellular vesicles, and engineered tissues by enhancing cell viability, mitochondrial function, secretome activity, immunomodulation, and therapeutic potency. The Topic also encompasses biomaterial-based delivery systems, scaffold-assisted therapies, extracellular vesicle engineering, gene editing technologies, tissue engineering and biofabrication, and multi-omics approaches applied to regenerative medicine. Together, these strategies reflect the interdisciplinary effort required to accelerate the clinical translation of next-generation cell and gene therapies across multiple tissues and organ systems.We invite original research articles and reviews that advance the mechanistic understanding and translational application of these bioengineering strategies, with emphasis on reproducible experimental models, quantitative characterisation of engineered biological products, and therapeutic applications across multiple tissues and organ systems. Topics of interest include: • Photobiomodulation (LED and LLLT) as a tool for optimising therapeutic cells and engineered tissues• Advanced bioengineering strategies to enhance cell and gene therapy safety and efficacy• Biomaterial and scaffold-based delivery systems• Hydrogels, bioactive matrices, tissue patches, encapsulation, and injectable biomaterials• Extracellular vesicle and secretome engineering for tissue repair• Gene therapy and gene editing approaches in regenerative medicine• Multi-omics characterisation of engineered biological products• Tissue engineering and biofabrication strategies• Mitochondrial-targeted therapies and metabolic modulation in tissue regeneration Topic editors: Andrey Jorge Serra, Leonardo Carvalho, Asheesh Gupta Source: https://www.frontiersin.org/research-topics/82815/bioengineering-strategies-to-overcome-translational-barriers-in-cell-and-gene-therapy-for-tissue-repair