Biology subjects

Olutoye, O. O.

Publications and source records attributed to Olutoye, O. O..

3 recordsLinked to original sources

bioRxiv2022

Lignin Composites with Sustained Oxygenation and Reactive Oxygen Species-Scavenging Improve Neovascularization and Healing of Diabetic Wounds

Although delayed wound healing is an important clinical complication in diabetic patients, few targeted treatments are available, and it remains a challenge to promote diabetic wound healing. Impaired neovascularization is one of the prime characteristics of the diabetic phenotype of delayed wound healing. Additionally, increased levels of reactive oxygen species (ROS) and chronic low-grade inflammation and hypoxia are associated with diabetes, which disrupts mechanisms of wound healing. We developed lignosulfonate composites with several wound healing properties, including sustained oxygen release through calcium peroxide nanoparticles and reactive oxygen species (ROS) and free radical scavenging by thiolated lignosulfonate nanoparticles. Sustained release of oxygen and ROS-scavenging by these composites promoted endothelial cell branching and characteristic capillary-like network formation under high glucose conditions in vitro. Gene co-expression network analysis of RNA-sequencing results from ECs cultured on lignin composites showed regulation of inflammatory pathways, alongside the regulation of angiogenic hypoxia-inducible factor-1 (HIF-1a) and vascular endothelial growth factor (VEGF) pathways. In vivo, lignosulfonate composite treatment promoted angiogenic growth factor expression and angiogenesis in full thickness skin wounds in diabetic (db/db) mice, a model of delayed wound healing. Treatment of diabetic wounds with lignosulfonate composites also promoted faster epithelial gap closure and increased granulation tissue deposition by day 7 post-wounding, with a higher presence of pro-healing type macrophages. These effects significantly improved tissue repair outcomes by day 14. Our findings demonstrate that lignosulfonate composites promote diabetic wound healing without requiring additional drugs. This highlights the potential of functionalized lignosulfonate for wound healing applications that requires balanced antioxidation and controlled oxygen release. Statement of SignificanceThe lignosulfonate composites developed in this study offer a promising solution for delayed wound healing in diabetic patients. By effectively addressing key factors contributing to the multifaceted pathophysiology of the diabetic wounds, including impaired neovascularization, increased ROS levels, and chronic inflammation and wound proteolysis, these composites demonstrate significant potential for promoting wound repair and reducing the complications associated with diabetic wounds. The unique combination of pro-angiogenic, oxygen-releasing, ECM remodeling and antioxidant properties in these lignosulfonate-based materials highlights their potential as a valuable therapeutic option, providing a novel approach to diabetic wound healing without the need for additional drugs.

bioengineering↗

bioRxiv2022

Defining Predictors of Successful Early Career to Independent Funding Conversion Among Surgeon-Scientists

IntroductionThe National Institutes of Health (NIH) provides research funding to scientists at different stages of their career through a range of grant awards. Early-stage researchers are eligible for mentored Career Development (K) awards, to aid in the transition to independent NIH funding. Factors such as education, subspecialty, and time to funding have been studied as predictors of obtaining independent awards in nonsurgical specialties. However, in surgery, the importance of these factors has yet to be clearly elucidated. We aim to identify predictors of K to independent award conversion among surgeon-scientists to understand how to better support early-stage researchers transitioning to independent careers. Materials and MethodsIn July 2020, the NIH Research Portfolio Online Reporting Tools database was queried for individuals affiliated with surgery departments who received NIH Career Development Awards (between 2000 and 2020). The following factors were analyzed: publications, institution, degrees, year of completion of training, and gender. ResultsBetween 2000 and 2020, 228 surgeons received K Awards, of which 44% transitioned to independent funding. On average, surgeons received a K award 4.0 years after completing fellowship training and an independent award 5.4 years after receiving a K grant. The time to receiving a K award was predictive of successfully achieving independent funding, and those with independent funding had a significantly greater number of publications per year of their K-award. ConclusionSurgeons successful in transitioning to independent NIH awards do so approximately 9 years after finishing fellowship. Publication track record is the main factor associated with successful conversion from a K award. Surgery departments should emphasize manuscript productivity and develop strategies to minimize time to independent funding to help K-awardees begin independent research careers.

scientific communication and education↗

bioRxiv2022

Endogenous IL-10 Contributes to Wound Healing and Regulates Tissue Repair

BackgroundInterleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well established. We sought to determine the role of IL-10 in murine full thickness, excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure. MethodsFull thickness, excisional wounds were made in wildtype (WT) and IL-10-/- mice on a C57BL/6J background (F/M, 8wks old). In a subset of wounds, contraction was prevented by splinting with silicone stents (stenting) and maintaining a moist wound microenvironment using a semi-occlusive dressing. Wounds were examined for re-epithelialization, granulation tissue deposition, and inflammatory cell infiltrate at day 7 and fibrosis and scarring at day 30 post-wounding. ResultsWe observed no difference in wound healing rate between WT and IL-10-/- mice in either the stented or unstented group. At day 7, unstented IL-10-/- wounds had a larger granulation tissue area and more inflammatory infiltrate than their WT counterparts. However, we did observe more F4/80+ cell infiltrate in stented IL-10-/- wounds at day 7. At day 30, stented wounds had increased scar area and epithelial thickness compared to unstented wounds. ConclusionsThese data suggest that endogenous IL-10 expression does not alter closure of full thickness excisional wounds when wound hydration and excessive contraction are controlled. However, the loss of IL-10 leads to increased inflammatory cell infiltration and scarring. These data suggest that previous reports of increased rates of healing in IL-10-/- mice ought to be revisited considering recent advances in wound healing models. Moreover, these new findings suggest that IL-10 contributes to regulation of inflammation without compromising the healing response.

molecular biology↗