Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction.

Shun Kimura,Takashi Tsuji

doi:10.3390/ijms22115474

Abstract

In the past decade, a new frontier in scarless wound healing has arisen because of significant advances in the field of wound healing realised by incorporating emerging concepts from mechanobiology and immunology. The complete integumentary organ system (IOS) regeneration and scarless wound healing mechanism, which occurs in specific species, body sites and developmental stages, clearly shows that mechanical stress signals and immune responses play important roles in determining the wound healing mode. Advances in tissue engineering technology have led to the production of novel human skin equivalents and organoids that reproduce cell–cell interactions with tissue-scale tensional homeostasis, and enable us to evaluate skin tissue morphology, functionality, drug response and wound healing. This breakthrough in tissue engineering has the potential to accelerate the understanding of wound healing control mechanisms through complex mechanobiological and immunological interactions. In this review, we present an overview of recent studies of biomechanical and immunological wound healing and tissue remodelling mechanisms through comparisons of species- and developmental stage-dependent wound healing mechanisms. We also discuss the possibility of elucidating the control mechanism of wound healing involving mechanobiological and immunological interaction by using next-generation human skin equivalents.

Highlights

The integumentary organ system (IOS), including skin and skin appendages such as hair, sebaceous glands, sweat glands, feathers, and nails, plays an essential role in protecting deeper tissues from extrinsic stress, such as dryness, chemical compounds, ultraviolet, and mechanical stress [1]
We provide an overview of the control mechanism of wound healing induced by mechanical stress and the immune response, and discuss the possibility of wound treatment strategies that do not cause hypertrophic scarring (HTS) or keloid formations
In the proliferation phase of Mus musculus and Homo sapiens, mechanical stress is applied to dermal cells according to the contraction of the wound site, and dermal fibroblasts differentiate into alpha smooth muscle actin positive myofibroblasts, which induce wound site contraction and extracellular matrix (ECM) deposition [24]

Summary

Introduction

The integumentary organ system (IOS), including skin and skin appendages such as hair, sebaceous glands, sweat glands, feathers, and nails, plays an essential role in protecting deeper tissues from extrinsic stress, such as dryness, chemical compounds, ultraviolet, and mechanical stress [1]. These external stresses cause microscale damage, such as protein denaturation and degradation, cellular senescence, apoptosis and abnormal differentiation, and macroscopic tissue damage, such as wounds and fibrosis. We provide an overview of the control mechanism of wound healing induced by mechanical stress and the immune response, and discuss the possibility of wound treatment strategies that do not cause HTS or keloid formations

Mechanical Regulation in Wound Healing

Immune Response Regulates Myofibroblast Differentiation and Function

Mechanical Stress Controls Macrophage Function

In Vitro

Findings

Future Perspective