ChE 5895 Special Topics: Biomimetic Formulations (3 cr) - Spring 2008
Instructor: John H. Brekke, DDS
UMD Chemical Engineering – Lab 112 & 171: (218) 726-8311
Contact At Home Office: (218) 525-3867
Recent advances in cell and molecular biology, together with development of sophisticated biomaterials, have unlocked therapeutic potentials that not long ago would have been consigned to tales of science fiction. However, the very real healing benefits of these advances can not become clinical realities until cell biologists, engineers of all stripes and clinicians integrate their disparate talents into new approaches for providing adult tissue regeneration. To this end, we present a study of tissue engineering, based on principles of cell biology and materials engineering, employed in a construct designed as a minimally invasive treatment for lower back pain.
Intervertebral disc (IVD) degeneration results in chronic back pain exposing the US to over $30 billion in annual direct health care costs and $100 billion more of indirect costs to society at large. Human IVDs are composite structures of a gelatinous internal nucleus pulposus (NP) surrounded by a more rigid lamellar annulus fibrosus (AF). NP consists of chondrocyte-like cells suspended in a meshwork of proteoglycans and Type II collagen. Interactions between the rigid AF and the NP maintain normal biomechanical homeostasis and integrity of the IVD. NP degeneration is characterized by loss of proteoglycans, decreased synthesis and increased denaturation of Type II collagen and progressive dehydration. Alteration of NP composition results in loss of its normal mechanical and biochemical functions leading to symptomatic musculoskeletal disorders of the spine; lower back pain.
The adjacent figure shows microscopic fibers of hyaluronan (HY) and chitosan (CT) formed as a polyelectrolytic complex (PEC) within a hydrogel of unreacted hyaluronan and chitosan. This composite material, 93% water, is a candidate for rehydration of deteriorated NP and could be considered as a culture matrix for stem cells differentiation to chondrocyte-like cells appropriate for seeding to the (NP). ChE 5895 will fabricate this 3-D hydrogel matrix, seed it with human mesenchymal stem cells and differentiate these cells toward the chondrocyte phenotype. If successful, this system would become an embryonic tissue capable of treating degenerative NP tissue by rehydration, implantation of a viable chondrocyte cell population, increased concentrations of proteoglycans and Type II collagen as well as integration of exogenous HY and CT into existing proteoglycans of host tissue.