RESUMEN
This cohort study compares the clinical features and outcomes of dermatomyositis between Hispanic and non-Hispanic patients.
RESUMEN
Despite the advancements in skin bioengineering, 3D skin constructs are still produced as flat tissues with open edges, disregarding the fully enclosed geometry of human skin. Therefore, they do not effectively cover anatomically complex body sites, e.g., hands. Here, we challenge the prevailing paradigm by engineering the skin as a fully enclosed 3D tissue that can be shaped after a body part and seamlessly transplanted as a biological clothing. Our wearable edgeless skin constructs (WESCs) show enhanced dermal extracellular matrix (ECM) deposition and mechanical properties compared to conventional constructs. WESCs display region-specific cell/ECM alignment, as well as physiologic anisotropic mechanical properties. WESCs replace the skin in full-thickness wounds of challenging body sites (e.g., mouse hindlimbs) with minimal suturing and shorter surgery time. This study provides a compelling technology that may substantially improve wound care and suggests that the recapitulation of the tissue macroanatomy can lead to enhanced biological function.
Asunto(s)
Bioingeniería , Matriz Extracelular , Humanos , Ingeniería , Ingeniería de TejidosAsunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Epidermólisis Ampollosa Distrófica/tratamiento farmacológico , Quinasas Janus/antagonistas & inhibidores , Pirazoles/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Administración Oral , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/complicaciones , Epidermólisis Ampollosa Distrófica/genética , Fibroblastos , Humanos , Quinasas Janus/metabolismo , Ratones , Mutación , Nitrilos , Pirazoles/farmacología , Pirimidinas , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective: We compared the capability of human umbilical vein endothelial cells (HUVECs), induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs), and human dermal blood endothelial cells (HDBECs) to effectively vascularize engineered human skin constructs (HSCs) in vitro and on immunodeficient mice. Approach: We quantified the angiogenesis within HSCs both in vitro and in vivo through computational analyses of immunofluorescent (IF) staining. We assayed with real-time quantitative PCR (RT-qPCR) the expression of key endothelial, dermal, and epidermal genes in 2D culture and HSCs. Epidermal integrity and proliferation were also evaluated through haematoxylin and eosin staining, and IF staining. Results: IF confirmed iEC commitment to endothelial phenotype. RT-qPCR showed HUVECs and iECs immaturity compared with HDBECs. In vitro, the vascular network extension was comparable for HDBECs and HUVECs despite differences in vascular diameter, whereas iECs formed unorganized rudimentary tubular structures. In vivo, all ECs produced discrete vascular networks of varying dimensions. HUVECs and HDBECs maintained a higher proliferation of basal keratinocytes. HDBECs had the best impact on extracellular matrix expression, and epidermal proliferation and differentiation. Innovation: To our knowledge, this study represents the first direct and quantitative comparison of HDBECs, HUVECs, and iECs angiogenic performance in HSCs. Conclusions: Our data indicate that HUVECs and iECs can be an alternative cell source to HDBEC to promote the short-term viability of prevascularized engineered grafts. Nevertheless, HDBECs maintain their capillary identity and outperform other EC types in promoting the maturation of the dermis and epidermis. These intrinsic characteristics of HDBECs may influence the long-term function of skin grafts.