Charles Hwang

Local and Circulating Endothelial Cells Undergo Endothelial to Mesenchymal Transition (EndMT) in Response to Musculoskeletal Injury

Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of aberrant wound healing conditions. However, unambiguous evidence of EndMT has been elusive due to limitations of in vitro experimental designs and animal models. In vitro experiments cannot account for the myriad ligands and cells which regulate differentiation, and in vivo tissue injury models may induce lineage-independent endothelial marker expression in mesenchymal cells. By using an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior to injury, we demonstrate that musculoskeletal injury induces expression of CD31, VeCadherin, or Tie2 in mesenchymal cells. VeCadherin and Tie2 were expressed in non-endothelial cells (CD31−) present in marrow from uninjured adult mice, thereby limiting the specificity of these markers in inducible models (e.g. VeCadherin- or Tie2-creERT). However, cell transplantation assays confirmed that endothelial cells (ΔVeCadherin/CD31+/CD45−) isolated from uninjured hindlimb muscle tissue undergo in vivo EndMT when transplanted directly into the wound without intervening cell culture using PDGFRα, Osterix (OSX), SOX9, and Aggrecan (ACAN) as mesenchymal markers. These in vivo findings support EndMT in the presence of myriad ligands and cell types, using cell transplantation assays which can be applied for other pathologies implicated in EndMT including tissue fibrosis and atherosclerosis. Additionally, endothelial cell recruitment and trafficking are potential therapeutic targets to prevent EndMT.

Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift.

Heterotopic ossification (HO) is the growth of extra-skeletal bone which occurs following trauma, burns, and in patients with genetic bone morphogenetic protein (BMP) receptor mutations. The clinical and laboratory evaluation of HO is dependent on radiographic imaging to identify and characterize these lesions. Here we show that despite its inadequacies, plain film radiography and single modality microCT continue to serve as a primary method of HO imaging in nearly 30% of published in vivo literature. Furthermore, we demonstrate that detailed microCT analysis is superior to plain film and single modality microCT radiography specifically in the evaluation of HO formed through three representative models due to its ability to 1) define structural relationships between growing extra-skeletal bone and normal, anatomic bone, 2) provide accurate quantification and growth rate based on volume of the space-occupying lesion, thereby facilitating assessments of therapeutic intervention, 3) identify HO at earlier times allowing for evaluation of early intervention, and 4) characterization of metrics of bone physiology including porosity, tissue mineral density, and cortical and trabecular volume. Examination of our trauma model using microCT demonstrated two separate areas of HO based on anatomic location and relationship with surrounding, normal bone structures. Additionally, microCT allows HO growth rate to be evaluated to characterize HO progression. Taken together, these data demonstrate the need for a paradigm shift in the evaluation of HO towards microCT as a standard tool for imaging.

Optimizing value of colon surgery in Michigan

Objective: To assess the value of bundling perioperative care measures in colon surgery. Background: Surgical site infections (SSI) in colectomy are associated with increased morbidity and cost. Perioperative care bundling has been designed to improve processes of care surrounding colectomy operations. Methods: Retrospective cohort study performed by the Michigan Surgical Quality Collaborative (MSQC) of patients who underwent elective colon surgery from 2012 to 2015. We identified 3,387 patients in the MSQC database who underwent colon surgery. Of these cases, 332 had associated episodic cost data. Results: High compliance (3–6 bundle elements) and low compliance (0–2 bundle elements) had a risk-adjusted SSI rate of 8.2% (95% confidence interval, CI, 7.2–9.2%) and 16.0% (95% CI, 12.9–19.1%), respectively (P < 0.01). When compared with low compliance, the high compliance group had an absolute risk reduction of 3.6% (P < 0.01), 2.9% (P < 0.01) and 1.3% (P < 0.01) for SSI rates in superficial space, deep space, and organ space, respectively. Low compliance had an average episodic cost of

The systemic effect of burn injury and trauma on muscle and bone mass and composition

20,046 (95% CI,

Case Study: Foundations of a Successful Academic Surgery Development Program

17,281–

Combined reflectance and Raman spectroscopy to assess degree of in vivo angiogenesis after tissue injury

22,812) whereas high compliance had an episodic cost of

Abstract 09: Changing The Paradigm For A Rare Genetic Disease That Is Currently Contraindicated For Surgery and Lacks Alternative Treatments

15,272 (95% CI,

Abstract QS52: Musculoskeletal Polytrauma In The Setting of Ischemia/reperfusion Results In Increased Intramuscular Inflammation and Recruitment of Circulatory Macrophages

14,354–

Abstract 26: Identifying The Role of and Treatment Targeting Bone Progenitor Cell VEGF Secretion On The Niche Supporting Traumatic Heterotopic Ossification

16,192). This showed a

Abstract 60: Tuning The Immune Response To Improve Musculoskeletal Extremity Trauma Wound Healing Through Macrophage Directed Tgfb1 Modification

4,774 (95% CI,