Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

Abstract

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications.

3D-printed placental-derived bioinks for skin tissue regeneration with improved angiogenesis and wound healing properties

“…Over the years, engineered skin replacements have been used as a new tool to treat deep wounds. Along these lines, the main challenge has always been to restore the angiogenic potential that is severely affected in deep wounds [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]. As we speak, no skin alternatives in the market can promote collagen production, cell proliferation, and especially angiogenesis while reducing infection.…”

Bioengineering Skin Substitutes for Wound Management—Perspectives and Challenges

“…The role of macrophages is to migrate towards sites of inflammation. There, they become activated, where they ultimately polarize towards pro-inflammatory M1 and anti-inflammatory M2 states [133].…”

“…The prolonged presence of M1 macrophages prolongs the inflammatory phase. On the other hand, the prolonged presence of M2 macrophages may result in the formation of detrimental foreign body giant cells [133].…”

The Use of Hydrogel-Based Materials for Radioprotection

“…These MSCs exhibit robust regenerative capabilities in models of tissue injury including diabetes- and burn-related wound model systems, making them promising tools that can be leveraged to treat radiation-related skin damage [ 54 , 55 , 56 ]. Hydrogels represent an ideal tool for MSC delivery owing to their excellent biocompatibility, biodegradability, and mechanical properties [ 57 ]. Lee et al [ 58 ], for example, utilized the ECM-based pig small intestinal submucosa (SIS) for hydrogel preparation, incorporating MSCs derived from human umbilical cord blood (hUCB) into this scaffold.…”