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.