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Abstract Platelets crucially facilitate wound healing but can become depleted in traumatic injury or chronic wounds. Previously, our group developed injectable platelet‐like particles (PLPs) comprised of highly deformable, ultralow crosslinked pNIPAm microgels (ULCs) coupled to fibrin binding antibodies to treat post‐trauma bleeding. PLP fibrin‐binding facilitates homing to sites of injury, promotes clot formation, and, due to high particle deformability, induces clot retraction. Clot retraction augments healing by increasing clot stability, enhancing clot stiffness, and promoting cell migration into the wound bed. Because post‐traumatic healing is often complicated by infection, the objective of these studies was to develop antimicrobial nanosilver microgel composite PLPs to augment hemostasis, fight infection, and promote healing post‐trauma. A key goal was to maintain particle deformability following silver incorporation to preserve PLP‐mediated clot retraction. Clot retraction, antimicrobial activity, hemostasis after trauma, and healing after injury were evaluated via confocal microscopy, colony‐forming unit assays, a murine liver trauma model, and a murine full‐thickness injury model in the absence or presence of infection, respectively. We found that nanosilver incorporation does not affect base PLP performance while bestowing significant antimicrobial activity and enhancing infected wound healing outcomes. Therefore, Ag‐PLPs have great promise for treating hemorrhage and improving healing following trauma.
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A multiscale hybrid mathematical model of epidermal‐dermal interactions during skin wound healing
Abstract Following injury, skin activates a complex wound healing programme. While cellular and signalling mechanisms of wound repair have been extensively studied, the principles of epidermal‐dermal interactions and their effects on wound healing outcomes are only partially understood. To gain new insight into the effects of epidermal‐dermal interactions, we developed a multiscale, hybrid mathematical model of skin wound healing. The model takes into consideration interactions between epidermis and dermis across the basement membrane via diffusible signals, defined as activator and inhibitor. Simulations revealed that epidermal‐dermal interactions are critical for proper extracellular matrix deposition in the dermis, suggesting these signals may influence how wound scars form. Our model makes several theoretical predictions. First, basal levels of epidermal activator and inhibitor help to maintain dermis in a steady state, whereas their absence results in a raised, scar‐like dermal phenotype. Second, wound‐triggered increase in activator and inhibitor production by basal epidermal cells, coupled with fast re‐epithelialization kinetics, reduces dermal scar size. Third, high‐density fibrin clot leads to a raised, hypertrophic scar phenotype, whereas low‐density fibrin clot leads to a hypotrophic phenotype. Fourth, shallow wounds, compared to deep wounds, result in overall reduced scarring. Taken together, our model predicts the important role of signalling across dermal‐epidermal interface and the effect of fibrin clot density and wound geometry on scar formation. This hybrid modelling approach may be also applicable to other complex tissue systems, enabling the simulation of dynamic processes, otherwise computationally prohibitive with fully discrete models due to a large number of variables.
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- Award ID(s):
- 1763272
- PAR ID:
- 10461151
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Experimental Dermatology
- Volume:
- 28
- Issue:
- 4
- ISSN:
- 0906-6705
- Page Range / eLocation ID:
- p. 493-502
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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