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

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.

Preliminary Characterization of a Polycaprolactone-SurgihoneyRO Electrospun Mesh for Skin Tissue Engineering

Skin is a hierarchical and multi-cellular organ exposed to the external environment with a key protective and regulatory role. Wounds caused by disease and trauma can lead to a loss of function, which can be debilitating and even cause death. Accelerating the natural skin healing process and minimizing the risk of infection is a clinical challenge. Electrospinning is a key technology in the development of wound dressings and skin substitutes as it enables extracellular matrix-mimicking fibrous structures and delivery of bioactive materials. Honey is a promising biomaterial for use in skin tissue engineering applications and has antimicrobial properties and potential tissue regenerative properties. This preliminary study investigates a solution electrospun composite nanofibrous mesh based on polycaprolactone and a medical grade honey, SurgihoneyRO. The processing conditions were optimized and assessed by scanning electron microscopy to fabricate meshes with uniform fiber diameters and minimal presence of beads. The chemistry of the composite meshes was examined using Fourier transform infrared spectroscopy and X-ray photon spectroscopy showing incorporation of honey into the polymer matrix. Meshes incorporating honey had lower mechanical properties due to lower polymer content but were more hydrophilic, resulting in an increase in swelling and an accelerated degradation profile. The biocompatibility of the meshes was assessed using human dermal fibroblasts and adipose-derived stem cells, which showed comparable or higher cell metabolic activity and viability for SurgihoneyRO-containing meshes compared to polycaprolactone only meshes. The meshes showed no antibacterial properties in a disk diffusion test due to a lack of hydrogen peroxide production and release. The developed polycaprolactone-honey nanofibrous meshes have potential for use in skin applications.

Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering

Conductive biomaterials based on conductive polymers, carbon nanomaterials, or conductive inorganic nanomaterials demonstrate great potential in wound healing and skin tissue engineering, owing to the similar conductivity to human skin, good antioxidant and antibacterial activities, electrically controlled drug delivery, and photothermal effect. However, a review highlights the design and application of conductive biomaterials for wound healing and skin tissue engineering is lacking. In this review, the design and fabrication methods of conductive biomaterials with various structural forms including film, nanofiber, membrane, hydrogel, sponge, foam, and acellular dermal matrix for applications in wound healing and skin tissue engineering and the corresponding mechanism in promoting the healing process were summarized. The approaches that conductive biomaterials realize their great value in healing wounds via three main strategies (electrotherapy, wound dressing, and wound assessment) were reviewed. The application of conductive biomaterials as wound dressing when facing different wounds including acute wound and chronic wound (infected wound and diabetic wound) and for wound monitoring is discussed in detail. The challenges and perspectives in designing and developing multifunctional conductive biomaterials are proposed as well.