Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.A...Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.展开更多
基金The reported study was supported in part by research grants from the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113)(JF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JF)+9 种基金the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(No.CY200409)(JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JF)and the National Key Research and Development Program of China(2016YFC1000803)RRR,TCH and GAA were partially funded by the National Institutes of Health(DE030480)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was also supported by the Mabel Green Myers Research Endowment Fund,The University of Chicago Orthopaedics Alumni Fund,and The University of Chicago SHOCK Fund.Funding sources were not involved in the study designin the collection,analysis and/or interpretation of datain the writing of the reportor in the decision to submit the paper for publication.
文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.