Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing.

Anthropogenic disturbances involving land use change, climate disruption, pollution and invasive species have been shown to impact immune function of wild animals. These immune changes have direct impacts on the fitness of impacted animals and, also, potentially indirect effects on other species and on ecological processes, notably involving the spread of infectious disease. Here, we investigate whether the selective loss of large wildlife can also drive changes in immune function of other consumer species. Using a long-standing large-scale exclosure experiment in East Africa, we investigated the effects of selective removal of large wildlife on multiple measures of immune function in the dominant small rodent in the system, the East African pouched mouse, Saccostomus mearnsi. We find support for a general increase in immune function in landscapes where large wildlife has been removed, but with some variation across immune parameters. These changes may be mediated in part by increased pathogen pressure in plots where large wildlife has been removed due to major increases in rodent density in such plots, but other factors such as changes in food resources are also likely involved. Overall, our research reveals that the elimination of large-bodied wildlife - now recognized as another major form of global anthropogenic change - may have cascading effects on immune health, with the potential for these effects to also impact disease dynamics in ecological communities. Lay Summary Functional Ecology