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

Abstract

Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

Supramolecular Biopolymers for Tissue Engineering

“…On the other hand, Zheng et al designed a silk-based nanofiber that allowed scarless skin regeneration in functional tissue. In a microsphere conformation, the nanofiber imbues and disperses mesenchymal stem cells into an injectable hydrogel to simulate paracrine signaling and induce scarless skin regeneration with hair follicles (Figures 4(b) and 4(c)) [65]. The in vivo studies reveal an improvement and outstanding novelty compared to other traditional biomaterial systems, presenting a reliable TE method in the applications of nanofibers for wound healing.…”

“…Genetic Tools Biomechanics Figure 2: TE is built on the following important pillars comprised of the development of organ and tissue architecture, bioengineering techniques, and material science. SBPs are involved in all these three pillars of TE with the aim to develop tissue-specific constructs for a variety of complex human organ systems; nowadays, SBPs have proven resourceful for the proliferation of neurons [60], endothelial cells [61], kidney cells [62], fibroblasts [63], osteocytes from mesenchymal stem cells [64], and complex skin regeneration [65]. SBPs can be used cooperatively with other technologies to create versatile and smart scaffolds for TE.…”

“…The results show that the material retains a hierarchical, aligned structure. These figures have been reproduced with permission from the American Chemical Society and John Wiley and Sons[65,105].…”

Attenuation corrected‐optical coherence tomography for quantitative assessment of skin wound healing and scar morphology

“…Further, in adult mammals timely wound healing results in normal scars [7], while pathological scarring (hypertrophic scars, keloids) is linked with prolonged inflammation and delayed healing [6]. Thus continuous in vivo imaging for quantifying the healing rate and scar/wound matrix morphologies can help evaluate the efficacy of therapeutic intervention (drugs) [8], engineered scaffolds/hydrogels [9], specific cells [10], biomolecules [7], and gene‐level alterations [11] for pre‐clinical/clinical studies to effect faster wound healing with low scarring (i.e., improved tissue restoration).…”

Hydrogel-Based Technologies for the Diagnosis of Skin Pathology

“…Few examples include the development of thermoresponsive composite hydrogel achieving moisture management and drug delivery for atopic dermatitis, thermoresponsive chitosan hydrogel facilitating microenvironment alteration and skin wound healing, as well as injectable micelle/hydrogel composites as curcumin-delivering wound dressing with accelerated healing and antibacterial activity [34][35][36]. In other studies, cells-laden hydrogels are employed to enable stable engraftment and survival of therapeutic cells (e.g., mesenchymal stem cells/MSCs) to promote vascularization and scar-less wound healing [37,38]. To a lesser extent, hydrogels are also developed to achieve diagnosis and monitoring of these pathological skin conditions.…”