To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation… [more]
Regeneration of skeletal muscle after volumetric injury is thought to be impaired by a dysregulated immune microenvironment that hinders endogenous repair mechanisms. Such defects result in fatty infiltration, tissue scarring, chronic inflammation, and debilitating functional deficits. Here, we evaluated the key cellular processes driving dysregulation in the injury niche through localized modulation of sphingosine‐1‐phosphate (S1P) receptor signaling. We employ dimensionality reduction and pseudotime analysis on single cell cytometry data to reveal heterogeneous immune cell subsets infiltrating preclinical muscle defects due to S1P receptor inhibition. We show that global knockout of S1P receptor 3 (S1PR3) is marked by an increase of muscle stem cells within injured tissue, a reduction in classically activated relative to alternatively activated macrophages, and increased bridging of regenerating myofibers across the defect. We found that local S1PR3 antagonism via nanofiber delivery of VPC01091 replicated key features of pseudotime immune cell recruitment dynamics… [more]
Inflammation after traumatic injury or surgical intervention is both a protective tissue response leading to regeneration and a potential cause of wound complications. One potentially successful strategy to harness to pro-regenerative roles of host inflammation is the localized delivery of bioactive materials to induce immune suppressive cellular responses by cells responding to injury. In this study, we designed a fully synthetic poly (ethylene) glycol (PEG)-based hydrogel to release the specialized pro-resolving lipid mediator aspirin-triggered resolvin-D1 (AT-RvD1) and recombinant human interleukin 10 (IL-10). We utilized a unique side-by-side internally controlled implant design wherein bioactive hydrogels… [more]
Award recognizes outstanding achievements in the field of biomaterials research
Edward Botchwey, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, received the 2019 Mid-Career Award from the Society For Biomaterials (SFB). This prestigious award is specifically given to recognize an individual who has demonstrated outstanding achievements in the field of biomaterials research with more than ten years and less than 20 years following his/her terminal degree or formal training.
Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of in ammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in in amed tissues and their subsequent interactions with implanted materials is necessary to guide the design … [more]
Omega-3 polyunsaturated fatty acid-derived resolvins are gaining increasing recognition for their essential roles in inhibition of neutrophil invasion into inflamed tissue and promotion of macrophage phagocytosis of cellular debris as well as their egress to the lymphatics. Biomaterial-based release of lipid mediators is a largely under-explored approach more …
Hematopoietic stem and progenitor cells (HSPCs) egress from bone marrow (BM) during homeostasis and at incrased rates during stress; however, the mechanisms regulating their trafficking remain incompletely understood. Here we describe a novel role for lipid receptor, sphingosine-1-phosphate receptor 3 (S1PR3), in HSPC residence within the BM niche. HSPCs more …
The American Institute for Medical and Biological Engineering (AIMBE) has announced the pending induction of Dr. Edward Botchwey to its College of Fellows for outstanding contributions to immunoregulatory biomaterials and national leadership in biomedical engineering. Each year, fellows are nominated by their peers in the medical and biological engineering community, and a select few are chosen to represent the “life-blood of AIMBE’s vision to provide medical and biological engineering innovation for the benefit of humanity.” The AIMBE College of Fellows recognizes the top 2% of outstanding bioengineers in academia, industry and government.