Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Abstract

Structural properties of biomaterials play critical roles in guiding cell behaviors and influence the immune response against them. In this study, we fabricated electro-spun membranes with three types of surface topography (Random, Aligned, and Latticed). The aligned membranes showed immunomodulatory ability, and led to faster wound healing, reduced fibrotic response and enhanced regeneration of cutaneous appendages. Based on that, we performed single-cell RNA sequencing analysis on cells of wounded mouse skin in the presence/absence of the Aligned scaffold. We identified 45 cell populations. Keratinocytes, fibroblasts, and immune cells including neutrophils, monocytes, macrophages, dendritic cells, and T cells showed diverse cellular heterogeneity. We found more inner root sheath cells (anagen-related) in the Aligned group, which corresponded to the improved regeneration of hair follicles in the presence of scaffold. The immune microenvironment around the biomaterial involved intricate interplay of immune cells from both innate and adaptive immune system. Immune responses in tissue around scaffold significantly differed from that of saline control. In aligned samples, infiltrated macrophages and neutrophils were reduced, whereas more effector T cells were recruited. The time course of immune response might be advanced towards an adaptive immunity-dominant stage by scaffolds.

Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

“…After a series of in vitro studies, we applied a subcutaneous implantation model to evaluate effect of ion-doped hydroxyapatite on immune microenvironment as reported previously [ 35 ]. The critical-sized Sprague-Dawley (SD) rat cranial defect model was also used to evaluate the material's promoting effects on bone regeneration in vivo .…”

An overview of substrate stiffness guided cellular response and its applications in tissue regeneration

“…Immune system such as macrophage and adaptive T cell is also sensitive to the surrounding mechanical cues [ 147 ]. In fact, every scaffold, once implanted in vivo , will elicit a definitive host immune response [ 148 ]. Up to date, the macrophage plasticity was found to exhibit a reciprocal polarization behavior depending on substrate stiffness [ 147 ], and pro-inflammatory response activated by engineered materials is also likely to contribute to the disrupted tissue remodeling via regulating the secreted extracellular vesicle of relevant cells [ 149 ].…”

The diameter factor of aligned membranes facilitates wound healing by promoting epithelialization in an immune way

“…Aligned membranes could promote the normal differentiation and outgrowth of vascular smooth muscle cells [ 17 , 22 ]. Critically, previous research in our group has shown that aligned membranes have many advantages in soft tissue repair and can actively regulate the immune response [ 23 ].…”