Tracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration

Abstract

Skin scarring devoid of dermal appendages after severe trauma has unfavorable effects on aesthetic and physiological functions. Here we present a method for large-area wound regeneration using biodegradable aligned extracellular matrix scaffolds. We show that the implantation of these scaffolds accelerates wound coverage and enhances hair follicle neogenesis. We perform multimodal analysis, in combination with single-cell RNA sequencing and spatial transcriptomics, to explore the immune responses around biomaterials, highlighting the potential role of regulatory T cells in mitigating tissue fibrous by suppressing excessive type 2 inflammation. We find that immunodeficient mice lacking mature T lymphocytes show the typical characteristic of tissue fibrous driven by type 2 macrophage inflammation, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. These findings contribute to our understanding of the coordination of immune systems in wound regeneration and facilitate the design of immunoregulatory biomaterials in the future.

Microenvironment-responsive release of Mg2+from tannic acid decorated and multilevel crosslinked hydrogels accelerates infected wound healing

“…Persistent inflammation is a key characteristic of chronic wounds, and a shift from an inflammatory state to a proliferative one is recognized as a vital control point in wound healing. 1,29 After 12 days of treatment, immunohistochemistry staining images revealed an increase in the expression of TNF-a and IL-6 in the control group and the OHA-P/G hydrogel group, and a decrease in expression in the OHA-P-TA/G and OHA-P-TA/ G/Mg 2+ groups (Fig. 8(A) and Fig.…”

“…The treatment of infected wounds presents a great clinical challenge due to their high localized bacterial colonization. 1,2 Bacteria discharge a variety of substances that can instigate an intense and extended inflammatory response, undermine the extracellular matrix (ECM) in host tissues shortly after colonization and infection, and drastically impede the wound healing process. Inflammatory cells induced at the wound site generate large amounts of reactive oxygen species (ROS), leading to apoptosis and vascular damage, thereby inducing oxidative stress and prolonged inflammation.…”

“…Inflammatory cells induced at the wound site generate large amounts of reactive oxygen species (ROS), leading to apoptosis and vascular damage, thereby inducing oxidative stress and prolonged inflammation. 1,3,4 Moreover, the persistent inflammatory response further worsens the immune microenvironment of wound healing through the secretion of a large number of inflammatory factors, interrupting the transition of the wound healing process from the inflammatory phase to the proliferative phase. 5,6 Therefore, therapeutic strategies such as antioxidants, antimicrobials, antiinflammatories, and vascular regeneration can be used for the resolution of infected wounds to re-establish microenvironmental balance.…”

Modelling of macrophage responses to biomaterials in vitro: state-of-the-art and the need for the improvement

“…Evident expression of Notch2 around the implanted biomaterial was detected. Selective inhibitors of Notch signaling pathways effectively decreased M1-like macrophages and stimulated M2-like macrophages, through the support of the scaffold ( 79 ). Gong et al.…”

Advances and applications of biomimetic biomaterials for endogenous skin regeneration

“…A recent article revealed the mechanism of biomaterial scaffold to promote re-epithelialization of wounds and facilitate HF regeneration: Yang et al developed an electrospinning poly(lactide- co -glycolide) (PLGA)/fish collagen (FC) aligned extracellular matrix scaffold. That scaffold could accelerate wound coverage and suppress type 2 inflammation by modulating regulatory T cells, thereby reducing fibrosis and promoting HF regeneration [ 125 ]. Zhang et al fabricated a sandwich-structured wound dressing using hydrophilic zinc silicate bioceramics (ZnCS) and hydrophobic polylactic acid (PLA) by the technique of hot compression molding.…”