Biology subjects

CHU, C.

Publications and source records attributed to CHU, C..

3 recordsLinked to original sources

bioRxiv2022

Spatial exploration of immune cell heterogeneity in skin functional scar-less wound regeneration model at single-cell resolution

Inevitable skin scarring devoid of dermal appendages bring about unfavorable effects on both aesthetic and physiological functions. Here we offered an available method for large-area wound regeneration using biodegradable Aligned extracellular matrix (ECM) scaffold. Accelerating wound coverage and enhanced hair follicle (HF) neogenesis were observed with the implantation of biomaterials. Multimodal analysis during wound regeneration provides a unique lens through which we can explore the foreign body responses (FBR) around biomaterials. First, we identified cell heterogeneity in responses to ECM scaffolds using single-cell RNA sequencing. Next the spatial anchor highlighted preferential recruitment of T cells around biomaterials colocalized with hair follicle precursor cells. Reconstruction of signaling pathways suggested the pro-regenerative effect of the adaptive immune systems on HF neogenesis. Immunodeficient mice lacking mature T lymphocytes lost the ability to activate papillary fibroblast as well as stimulate HF regeneration, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. In conclusion, this study provided the further understanding of the FBR and facilitate the design of immunoregulatory biomaterials for biomedical application in the future.

immunology↗

bioRxiv2020

EGCG-modified bone graft to modulate the recruitment of M1 macrophage and alleviate the forming of fibrous capsule

In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone-material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its pro-fibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of pro-inflammatory macrophages, initial angiogenesis, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on pro-inflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less pro-inflammatory macrophage recruitment; meanwhile, the cell viability and primary angiogenesis were improved. This work lays the foundation for future studies on GBR.

immunology↗

bioRxiv2020

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Structural properties of biomaterials play critical roles in guiding cell behaviors and influence the immune response against them. We fabricated electrospun 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 when used in skin wound repair. Based on that, we performed single-cell RNA sequencing analysis on cells from wounded mouse skin in the presence or absence of the Aligned scaffold. Keratinocytes, fibroblasts, and immune cells including neutrophils, monocytes, macrophages, dendritic cells, and T cells showed diverse cellular heterogeneity. More hair follicle progenitor cells, inner root sheath cells (anagen-related) and fibroblast subsets were found in the Aligned group, which corresponded to the improved regeneration of hair follicles and faster wound closure in the presence of scaffold. Immune responses towards the biomaterial differed from that of control group. In aligned samples, infiltrated macrophages and neutrophils were reduced, whereas more effector T cells were recruited. The time course of immune response was possibly advanced towards an adaptive immunity-dominant stage by the scaffold. The microenvironment around scaffold involved intricate interplay of immune cells and cutaneous cells, and wound healing was the comprehensive results of numerous influencing factors working together.

immunology↗