Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals.

Abstract

Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively elucidate the mechanisms underlying this age-related disparity, we conducted an integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, to explore the complex cellular niches surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we identified and characterized the senescent SPP1+ macrophages may impede the activation of the type L immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.