Event

Bioengineering Seminar Series: Edward Botchwey

Friday, February 19, 2010
11:00 a.m.
Room 2110, Chemical and Nuclear Engineering Bldg.
Professor William Bentley
bentley@umd.edu

Harnessing Sphingosine 1-Phosphate (S1P) Receptor Selective Activation for Musculoskeletal Regeneration and Repair

Edward Botchwey
Assistant Professor
Biomedical Engineering & Orthopaedic Surgery
University of Virginia

There is an emerging appreciation of the interactions among the microcirculation and both the immune and skeletal systems during bone homeostasis and repair. With this in mind, our laboratory is working to exploit the diverse biological functions of Sphingosine1-phosphate (S1P) for healing and regeneration of musculoskeletal tissues. S1P is a pleiotropic autocrine and paracrine signaling small lipid molecule that directs biological responses through a family of high-affinity G protein-coupled receptors (S1P1–S1P5). Our studies interrogate the cooperative functions of S1P1 and S1P3 subtype activation in the microvasculature to promote inflammation resolution and bone healing. We show that sustained delivery of S1P1/S1P3 receptor selective drug FTY720 from biodegradable polymers suppresses inflammatory cell recruitment and promotes microvascular network maturation through the proliferation and recruitment of upstream smooth muscle cells (SMCs) and pericytes (‘mural support cells’) to nascent microvessels. In addition, implantation of 3D scaffolds delivering FTY720 to critical size calvarial bone defects significantly increases osseous tissue ingrowth and the proportion of mature SMC-invested microvessels in bony repair tissue. In pre-clinical model of massive allograft incorporation into critical size rat tibial defects, sustained release of FTY720 from coated allograft samples promotes significant new bone formation and osseointegration with host bone. These studies strongly suggest that pharmacological modulation of the S1P receptor signaling axis could have broad clinical applications in tissue engineering and regenerative medicine.

Audience: Graduate  Faculty  Post-Docs