Instructive microenvironments in skin wound healing: Biomaterials as signal releasing platforms

Abstract

Skin wound healing aims to repair and restore tissue through a multistage process that involves different cells and signalling molecules that regulate the cellular response and the dynamic remodelling of the extracellular matrix. Nowadays, several therapies that combine biomolecule signals (growth factors and cytokines) and cells are being proposed. However, a lack of reliable evidence of their efficacy, together with associated issues such as high costs, a lack of standardization, no scalable processes, and storage and regulatory issues, are hampering their application. In situ tissue regeneration appears to be a feasible strategy that uses the body's own capacity for regeneration by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the wound site to promote repair and regeneration. The aim is to engineer instructive systems to regulate the spatio-temporal delivery of proper signalling based on the biological mechanisms of the different events that occur in the host microenvironment. This review describes the current state of the different signal cues used in wound healing and skin regeneration, and their combination with biomaterial supports to create instructive microenvironments for wound healing.

Wound healing-promoting effects stimulated by extracellular calcium and calcium-releasing nanoparticles on dermal fibroblasts

“…[13,14,15] One of the most important objectives in tissue engineering is to direct cell behavior by achieving full control of their surrounding microenvironment. [26] Nanotechnology provides efficient tools to introduce suitable signals in biomaterials, allowing us to turn these microenvironments into regenerative milieus. Recently, novel bioactive nanostructured glasses have been designed, named calcium-phosphate organically modified glasses (CaP ormoglasses), that allow a more tunable behavior of the ion release, thus improving their instructive capacity.…”

Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration

“…PDGF, IL-1, IL-18, and other pro-inflammatory cytokines attract neutrophils to the injury site where they secrete proteases, reactive oxygen species, and phagocytose cell debris and pathogens, if present (Jorch and Kubes, 2017). Moreover, recruited neutrophils secrete TNF-α, IL-1, IL-6, and chemokines that stimulate migration of the cells of the immune system, including monocytes (Castano et al, 2018). Recruited monocytes differentiate into either pro-inflammatory macrophages, which produce TNFα, IL-1β, or reparative macrophages, which secrete IL-10 and TGF-β (Brazil et al, 2019).…”

“…Macrophages also phagocytose the remaining debris and apoptotic neutrophils, as well as stimulate fibroblast infiltration. Migrated fibroblasts produce matrix metalloproteinases that facilitate the removal of disorganized extracellular matrix and create space for newly created components of the extracellular matrix (Castano et al, 2018). TGF-β is a proliferation and differentiation factor of fibroblasts, which differentiate into myofibroblasts that close the area of injury (Martin and Nunan, 2015;Brazil et al, 2019).…”

“…In addition, VEGF, along with FGF, leads to the proliferation of endothelial cells and thus angiogenesis, an essential and integral part of the proliferative phase during which new blood vessels form (Sun et al, 2014). This allows oxygen and nutrients to be delivered to the site of injury, lack of which may hinder the process of wound healing (Castano et al, 2018). EGF, TGF−α, and FGF promote epithelial cell motility and proliferation, leading to re-epithelization (Arwert et al, 2012;Cordeiro and Jacinto, 2013).…”

Wound healing and scar wars

“…This special issue provides insights into some of the molecular mechanisms inherent to wound healing and fibrosis [13][14][15][16] and highlighting the use of cell-and tissue-models for basic research and drug discovery [17,18]. The use of several approaches for treating or preventing such pathologies is also discussed, including bioactive [19][20][21], electroactive [22] and stimuli-responsive [23] biomaterialbased approaches; gene, drug, proteoglycan and growth factor based approaches [24][25][26][27][28][29][30][31][32][33][34]; cellular and cellular-derived based therapies [35][36][37]; and matrix modulation strategies [38]. Considering the significant strides made in understanding the molecular mechanisms operating in normal and pathological wound healing and the promising therapeutic approaches described herein, it is expected that in the near future, some of these technologies will satisfy clinical needs and enter commercialisation.…”