Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known pro-angiogenic and immunomodulatory paracrine effects. Our lab has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their pro-angiogenic capacity in vivo. Concurrently, recent research suggests that prospective isolation of cell subpopulations with desirable transcriptional profiles can be used to further improve cell-based therapies. In this study, we examined whether adipose-derived stem cell-seeded hydrogels could improve wound healing following thermal injury using a murine contact burn model. Partial thickness contact burns were created on the dorsum of mice. On days 5 and 10 following injury, burns were debrided and received either ASC-hydrogel, ASC injection alone, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis. This experiment was repeated using CD26+/CD55+ FACS-enriched ASCs to further evaluate the regenerative potential of ASCs in wound healing. ASC-hydrogel-treated burns demonstrated accelerated time to re-epithelialization, greater vascularity, and increased expression of the pro-angiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the pro-fibrotic gene Timp1 and pro-inflammatory gene Tnfa were down-regulated in ASC-hydrogel treated burns. ASC-hydrogel treated burns exhibited reduced scar area compared to hydrogel-treated and control wounds, with equivalent scar density. CD26+/CD55+ ASC-hydrogel treatment resulted in accelerated healing, increased dermal appendage count, and improved scar quality with a more reticular collagen pattern. Here we find that ASC-hydrogel therapy is effective for treating burns, with demonstrated pro-angiogenic, fibro-modulatory and immunomodulatory effects. Enrichment for CD26+/CD55+ ASCs has additive benefits for tissue architecture and collagen remodeling post-burn injury. Research is ongoing to further facilitate clinical translation of this promising therapeutic approach.

Wound healing is a complex, multi-phase process requiring coordinated interactions among diverse cell types and molecular pathways to restore tissue integrity. Dysregulation can lead to chronic non-healing wounds or excessive scarring, posing major clinical and economic burdens. Single-omics interrogate individual molecular layers, such as the genome, transcriptome, proteome, metabolome, or epigenome, and have revealed key cellular players, but provide a limited view of dynamic wound repair. Single-cell technologies provide higher resolution to single-omic data by resolving cell-type and state-specific heterogeneity, enabling precise characterization of cellular populations. Multi-omics integrates multiple molecular layers at single-cell resolution, reconstructing regulatory networks, epigenetic landscapes, and cell–cell interactions underlying healing outcomes. Recent advances in single-cell and spatial multi-omics have revealed fibroblast subpopulations with distinct fibrotic or regenerative roles and immune–epithelial interactions critical for re-epithelialization. Integration with computational tools and artificial intelligence (AI) continues to reveal cellular interactions, predict healing outcomes, and guide development of personalized therapies. Despite technical and translational challenges, including data integration and cost, multi-omics are increasingly shaping the future of precision wound care. This review highlights how multi-omics is redefining understanding of wound biology and fibrosis and explores emerging applications such as smart biosensors and predictive models with potential to transform wound care.

Diabetes mellitus is an increasingly prevalent chronic metabolic disorder characterized by physiologic hyperglycemia that, when left uncontrolled, can lead to significant complications in multiple organs. Diabetic wounds are common in the general population, yet the underlying mechanism of impaired healing in such wounds remains unclear. Single-cell RNA-sequencing (scRNAseq) has recently emerged as a tool to study the gene expression of heterogeneous cell populations in skin wounds. Herein, we review the history of scRNAseq and its application to the study of diabetic wound healing, focusing on how innovations in single-cell sequencing have transformed strategies for fibroblast analysis. We summarize recent research on the role of fibroblasts in diabetic wound healing and describe the functional and cellular heterogeneity of skin fibroblasts. Moreover, we highlight future opportunities in diabetic wound fibroblast research, with a focus on characterizing distinct fibroblast subpopulations and their lineages. Leveraging single-cell technologies to explore fibroblast heterogeneity and the complex biology of diabetic wounds may reveal new therapeutic targets for improving wound healing and ultimately alleviate the clinical burden of chronic wounds.