Wound Healing: A Cellular Perspective

Abstract

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. With the evolution of single cell technologies, it has been possible to uncover phenotypic and functional heterogeneity within several of these cell types. There have also been discoveries of rare, stem cell subsets within the skin, which are unipotent in the uninjured state, but become multipotent following skin injury. Unraveling the roles of each of these cell types and their interactions with each other is important in understanding the mechanisms of normal wound closure. Changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing. Single cell technologies can be used to decipher these cellular alterations in diseased states such as in chronic wounds and hypertrophic scarring so that effective therapeutic solutions for healing wounds can be developed.

Platelets exploit fibrillar adhesions to assemble fibronectin matrix revealing new force-regulated thrombus remodeling mechanisms

“…These findings point to so far unrecognized mechanisms how sensing and responding to their microenvironment is controlled by platelet contractility and we suggest that this contributes to the emergence of the structural heterogeneity of a thrombus. Our findings also challenge the common notion that the infiltration of fibroblasts or mesenchymal stem cells (Rodrigues et al 2019) is directed by the fibrin scaffold and that these infiltrating cells are the first to assemble a de novo Fn ECM (Singh, Carraher, and Schwarzbauer 2010;Barker and Engler 2017).…”

“…When blood vessels get injured, the massive recruitment and activation of platelets culminates in thrombus formation to stem bleeding, whereas the subsequent infiltration of the clot by immune and stromal cells is essential to ultimately restore tissue integrity (Rodrigues et al 2019). Platelet adhesion receptors initiate interactions with extracellular matrix (ECM) proteins that become exposed by endothelial barrier disruption, while platelet signaling receptors boost platelet aggregation and granule secretion.…”

Contribution of Angiogenesis to Inflammation and Cancer

“…VEGFR-2 dimerization induces the autophosphorylation of tyrosine residues and the activation of specific signaling pathways, including the PI3K and p38 MAPK pathways (36,37,40). In addition, conformational changes induced by receptor dimerization lead to an increase in intracellular Ca 2+ , the activation of PLCγ and endothelial nitric oxide synthase (eNOS), with the latter resulting in increased production of nitric oxide (NO) (41,42). In addition, Src kinase activation induces the phosphorylation of VE-cadherin and various catenins, preventing them from anchoring to the cytoskeleton (22,25,26).…”

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

“…[ 1 ] As a protective barrier to harmful external invasions, skin is easily damaged by trauma, disease, and chronic ulcers. [ 2 ] Serious skin defects to the depth of skeletal muscle are difficult to heal and usually form nonfunctional scar tissues even when treated with different biomaterial‐based wound dressings. Although bioactive biomaterials were developed to improve wound recovery, a challenge remains to regenerate scarless tissues with hair follicles.…”