Biomaterials for immunomodulation in wound healing.

The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients and the healthcare system. This review paper provides an overview of the skin's vital role in guarding against various environmental challenges as the body's largest protective organ and associated developments in biomaterials for wound healing. We first introduce the composition of skin tissue and the intricate processes of wound healing, with special attention to the crucial role of immunomodulation in both acute and chronic wounds. This highlights how the imbalance in the immune response, particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression, hinders normal healing stages. Then, this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure. Additionally, we highlight the importance of considering the stages of wounds in the healing process. By integrating advanced materials engineering with an in-depth understanding of wound biology, this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.

Angiopoietin-1 derived peptide hydrogel promotes molecular hallmarks of regeneration and wound healing in dermal fibroblasts.

By providing an ideal environment for healing, biomaterials can be designed to facilitate and encourage wound regeneration. As the wound healing process is complex, there needs to be consideration for the cell types playing major roles, such as fibroblasts. As a major cell type in the dermis, fibroblasts have a large impact on the processes and outcomes of wound healing. Prevopisly, conjugating the angiopoietin-1 derived Q-peptide (QHREDGS) to a collagen-chitosan hydrogel created a biomaterial with in vivo success in accelerating wound healing. This study utilized solvent cast Q-peptide conjugated collagen-chitosan seeded with fibroblast monolayers to investigate the direct impact of the material on this major cell type. After 24 h, fibroblasts had a significant change in release of anti-inflammatory, pro-healing, and ECM deposition cytokines, with demonstrated immunomodulatory effects on macrophages and upregulated expression of critical wound healing genes.

Application of an instructive hydrogel accelerates re-epithelialization of xenografted human skin wounds.

Poor quality (eg. excessive scarring) or delayed closure of skin wounds can have profound physical and pyschosocial effects on patients as well as pose an enormous economic burden on the healthcare system. An effective means of improving both the rate and quality of wound healing is needed for all patients suffering from skin injury. Despite wound care being a multi-billion-dollar industry, effective treatments aimed at rapidly restoring the skin barrier function or mitigating the severity of fibrotic scar remain elusive. Previously, a hydrogel conjugated angiopoietin-1 derived peptide (QHREDGS; Q-peptide) was shown to increase keratinocyte migration and improve wound healing in diabetic mice. Here, we evaluated the effect of this Q-Peptide Hydrogel on human skin wound healing using a mouse xenograft model. First, we confirmed that the Q-Peptide Hydrogel promoted the migration of adult human keratinocytes and modulated their cytokine profile in vitro. Next, utilizing our human to mouse split-thickness skin xenograft model, we found improved healing of wounded human epidermis following Q-Peptide Hydrogel treatment. Importantly, Q-Peptide Hydrogel treatment enhanced this wound re-epithelialization via increased keratinocyte migration and survival, rather than a sustained increase in proliferation. Overall, these data provide strong evidence that topical application of QHREDGS peptide-modified hydrogels results in accelerated wound closure that may lead to improved outcomes for patients.

Drawing Inspiration from Developmental Biology for Cardiac Tissue Engineers.

A sound understanding of developmental biology is part of the foundation of effective stem cell-derived tissue engineering. Here, the key concepts of cardiac development that are successfully applied in a bioinspired approach to growing engineered cardiac tissues, are reviewed. The native cardiac milieu is studied extensively from embryonic to adult phenotypes, as it provides a resource of factors, mechanisms, and protocols to consider when working toward establishing living tissues in vitro. It begins with the various cell types that constitute the cardiac tissue. It is discussed how myocytes interact with other cell types and their microenvironment and how they change over time from the embryonic to the adult states, with a view on how such changes affect the tissue function and may be used in engineered tissue models. Key embryonic signaling pathways that have been leveraged in the design of culture media and differentiation protocols are presented. The cellular microenvironment, from extracellular matrix chemical and physical properties, to the dynamic mechanical and electrical forces that are exerted on tissues is explored. It is shown that how such microenvironmental factors can inform the design of biomaterials, scaffolds, stimulation bioreactors, and maturation readouts, and suggest considerations for ongoing biomimetic advancement of engineered cardiac tissues and regeneration strategies for the future.