Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders

Abstract

Skin wound healing is essential to health and survival. Consequently, high amounts of research effort have been put into investigating the cellular and molecular components involved in the wound healing process. The use of animal experiments has contributed greatly to the knowledge of wound healing, skin diseases, and the exploration of treatment options. However, in addition to ethical concerns, anatomical and physiological inter-species differences often influence the translatability of animal-based studies. Human in vitro skin models, which include essential cellular and structural components for wound healing analyses, would improve the translatability of results and reduce animal experiments during the preclinical evaluation of novel therapy approaches. In this review, we summarize in vitro approaches, which are used to study wound healing as well as wound healing-pathologies such as chronic wounds, keloids, and hypertrophic scars in a human setting.

Macrostructure and Microenvironment Biomimetic Hydrogel: Design, Properties, and Tissue Engineering Application

“…129,130 Disrupted physiological microenvironments can significantly impact the synergy among these cells, leading to imbalanced cellular regulation and delayed tissue repair. 129,130 Another example, vascularization and osteogenesis play pivotal roles in tendon-to-bone interface healing. 127,131 However, alterations in the postoperative microenvironment of the tendon-to-bone interface are critical factors influencing the integration outcome.…”

“…Through the simulation of structural and mechanical properties in human organs, a substantial number of hydrogels have been developed, greatly advancing various fields including tissue repair, wound detection, and drug delivery. Moreover, tissue repair relies on the coordinated interaction of multiple cells. − For instance, in the healing process of skin injuries, various types of cells such as inflammatory cells, endothelial cells, and fibroblasts participate in different stages of healing, culminating in complete wound closure. , Disrupted physiological microenvironments can significantly impact the synergy among these cells, leading to imbalanced cellular regulation and delayed tissue repair. , Another example, vascularization and osteogenesis play pivotal roles in tendon-to-bone interface healing. , However, alterations in the postoperative microenvironment of the tendon-to-bone interface are critical factors influencing the integration outcome. , Therefore, biomimetic microenvironment modulation plays a crucial role in tissue repair.…”

“…125−128 For instance, in the healing process of skin injuries, various types of cells such as inflammatory cells, endothelial cells, and fibroblasts participate in different stages of healing, culminating in complete wound closure. 129,130 Disrupted physiological microenvironments can significantly impact the synergy among these cells, leading to imbalanced cellular regulation and delayed tissue repair. 129,130 Another example, vascularization and osteogenesis play pivotal roles in tendon-to-bone interface healing.…”

Automated In Vitro Wound Healing Assay

“…Cutaneous wound healing requires coordinated signaling across cell types in four major phases: hemostasis, inflammation, re-epithelialization, and tissue remodeling [1][2][3][4] (Figure 1). Injury to the skin triggers the formation of a fibrin clot to initially reestablish the epidermal barrier.…”

“…Immune cells attracted to the site of injury release bioactive factors that stimulate migration and proliferation of fibroblasts and keratinocytes. Activated fibroblasts reconstruct the extracellular matrix (ECM), while keratinocytes re-epithelialize the tissue [4, 5]. Disruptions to this system can lead to excessive scar formation or the development of diabetic ulcers, keloids, and other chronic non-healing wounds [4, 6, 7].…”