S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion

Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.

Expanded Forehead Stepped Flaps for Delayed Three-Stage Repair of Midface Skin Lesions

Background The forehead flap is the best flap for nasal defect repair and nasal reconstruction.It is also an ideal option for repairing skin lesions in the midface(including the nasal area,inner area of the cheek,and upper lip of the perioral area).However,the traditional frontal myocutaneous flap is relatively bulky for repairing pure skin lesions.In addition,the original forehead flap is generally not sufficient to cover a large wound area.If a large forehead flap is removed,the donor site cannot be sutured in one stage.In this study,an expanded forehead stepped flap was used to overcome the shortcomings of the traditional frontal myocutaneous flap.Methods In stage one surgery,a rectangular expander(80–100 mL)was implanted on the side of the forehead.The expansion pot was built-in,and the excess expansion amount was 160–200 mL.After 4 weeks of rest,stage two operation was performed to remove the skin lesions in the midface.The pulsation point of the supratrochlear artery on one side was used as the pedicle,and the flap was designed diagonally to the upper region of the opposite side.The flap was designed according to the size and shape of the wound.The distal portion of the flap was separated in the superficial layer of the frontalis muscle,approximately 1.7 cm above the superior orbital edge,and cut into the submuscle.The flap pedicle was cut from the superficial layer of the periosteum to form a stepped flap.Then,the flap was rotated downward to repair the wound in the midface.Five weeks later,stage three of the operation which involved flap pedicle division,was performed.Results Expanded forehead stepped flaps were used in 12 cases with 6–36 months of follow-up.In all cases,the blood supply to the flaps was good,and their color,texture,and thickness matched well with those of the surrounding skin.All patients were satisfied with the outcome of the repair.Conclusion Expanded forehead stepped flaps present an ideal option for repairing wounds after large skin lesion resections in the midface since they have multiple edges from a reliable blood supply,easiness to transfer,and well-matched color,texture,and thickness to those of the surrounding skin of the face to no need for many auxiliary incisions.