Mesenchymal stem cells,secretome and biomaterials in in-vivo animal models:Regenerative medicine application in cutaneous wound healing

The treatment of nonhealing and chronic cutaneous wounds still needs a clinical advancement to be effective.Both mesenchymal stem cells(MSCs),obtained from different sources,and their secretome derived thereof(especially exosomes)can activate signaling pathways related to promotion of cell migration,vascularization,collagen deposition,and inflammatory response demonstrating prohealing,angiogenetic and anti-scarring capacities.On the other hand,biodegradable biomimetic scaffolds can facilitate endogenous cell attachment and proliferation as well as extracellular matrix production.In this Review,we revise the complex composites made by biomimetic scaffolds,mainly hydrogels,and MSC-derived exosomes constructed for cutaneous wound healing.Studies demonstrate that there exists a synergistic action of scaffolds with encapsulated exosomes,displaying a sustained release profiles to facilitate longlasting healing effects.It can be envisioned that dressings made by biomimetic hydrogels and MSC-derived exosomes will be clinically applied in the near future for the effective treatment of nonhealing and chronic wounds.

Tailoring bioinks of extrusion-based bioprinting for cutaneous wound healing

Extrusion-based bioprinting (EBB) holds potential for regenerative medicine. However, the widely-used bioinks of EBB exhibit some limitations for skin regeneration, such as unsatisfactory bio-physical (i.e., mechanical, structural, biodegradable) properties and compromised cellular compatibilities, and the EBB-based bioinks with therapeutic effects targeting cutaneous wounds still remain largely undiscussed. In this review, the printability considerations for skin bioprinting were discussed. Then, current strategies for improving the physical properties of bioinks and for reinforcing bioinks in EBB approaches were introduced, respectively. Notably, we highlighted the applications and effects of current EBB-based bioinks on wound healing, wound scar formation, vasculari-zation and the regeneration of skin appendages (i.e., sweat glands and hair follicles) and discussed the challenges and future perspectives. This review aims to provide an overall view of the applications, challenges and promising solutions about the EBB-based bioinks for cutaneous wound healing and skin regeneration.

Therapeutic values of chick early amniotic fluid(ceAF)that facilitates wound healing via potentiating a SASP-mediated transient senescence

Inflammatory,proliferative and remodeling phases constitute a cutaneous wound healing program.Therapeutic applications and medication are available;however,they commonly are comprised of fortified preservatives that might prolong the healing process.Chick early amniotic fluids(ceAF)contain native therapeutic factors with balanced chemokines,cytokines and growth-related factors;their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development.Instead,they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions.Employing both in vitro and in vivo models,we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence,known to be intimately intermingled with Senescence Associated Secretory Phenotypes(SASP)that function in addition to or in conjunction with ceAF to facilitate wound healing.In our cutaneous wound healing models,a low dose of ceAF exhibited the best efficacies;however,higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold.Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing,suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence,expediting cellular proliferation,migration,and describing a homeostatic and balanced dosage strategy in medical intervention.