Development of a Three-Dimensional Human Skin Equivalent Wound Model for Investigating Novel Wound Healing Therapies

Abstract

Numerous difficulties are associated with the conduct of preclinical studies related to skin and wound repair. Use of small animal models such as rodents is not optimal because of their physiological differences to human skin and mode of wound healing. Although pigs have previously been used because of their human-like mode of healing, the expense and logistics related to their use also renders them suboptimal. In view of this, alternatives are urgently required to advance the field. The experiments reported herein were aimed at developing and validating a simple, reproducible, three-dimensional ex vivo de-epidermised dermis human skin equivalent wound model for the preclinical evaluation of novel wound therapies. Having established that the human skin equivalent wound model does in fact “heal," we tested the effect of two novel wound healing therapies. We also examined the utility of the model for studies exploring the mechanisms underpinning these therapies. Taken together the data demonstrate that these new models will have wide-spread application for the generation of fundamental new information on wound healing processes and also hold potential in facilitating preclinical optimization of dosage, duration of therapies, and treatment strategies prior to clinical trials.

Characterization of a Human Skin Equivalent Model to Study the Effects of Ultraviolet B Radiation on Keratinocytes

“…These HSEs may then be cultured at the air-liquid interface in order to promote keratinocyte differentiation and epidermogenesis. [20][21][22] This results in the formation of an epidermal layer that is histologically similar to native human skin. 21 These tissue-engineered constructs serve as versatile and powerful research tools with numerous applications, such as the study of cancer, pigmentation, and toxicity.…”

“…[20][21][22] This results in the formation of an epidermal layer that is histologically similar to native human skin. 21 These tissue-engineered constructs serve as versatile and powerful research tools with numerous applications, such as the study of cancer, pigmentation, and toxicity. 15 In this study, we characterize the novel application of a human keratinocyte-based HSE using a de-epidermized dermal (DED) culture substrate as a tool to investigate keratinocyte responses to UVB radiation.…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…Although there are several works demonstrating the printing of bi-layered skin constructs and evaluating their properties [156,164], there is a lack of studies using and testing their applicability for pharmaceutical or cosmetic testing. The majority of these studies employ skin equivalents exclusively created by manual methods [160,205] or fabricated using components obtained through 3D printing technologies combined with manual deposition of cell-laden solutions [122].…”

Keratinocyte Culture Techniques in Medical and Scientific Applications

“…Skin equivalents consisting of DED seeded with either keratinocytes or fibroblasts or both were developed. A full-thickness wound being inserted into the skin model decreased in the course of time, thus representing a wound model with the ability to heal (Xie et al, 2010). The growth factor VNGF was added to the wounds and resulted in an increased and earlier wound closure.…”