No abstract

In vitro and in vivo studies were conducted on Omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical cross-linking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure/function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of Omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.

In vitro, groups have demonstrated that peptide modified surfaces influence short and long term cell responses like attachment, shape and function via cell receptors known as integrins. These receptors translate information to the nucleus via sets of complex signaling pathways. Little is known about the ability of these surfaces to influence the inherently complex in vivo environment, however. The present study was designed to evaluate the quality and quantity of new bone formed in response to gold coated titanium rods modified with the peptide sequence Arg-Gly-Asp-Cys (RGDC). Quantitative histomorphometric analysis of histologic sections perpendicular to the implant long axis showed a thicker (P < 0.01) shell of new bone formed in response to peptide modified implants (26.2 microns ± 1.9 vs. 20.5 microns ± 2.9) as early as 2 weeks. Mechanical pull-out testing conducted at 4 weeks revealed the average pull-out force of peptide modified rods was 38% greater than gold control rods. The significant difference in the thickness of new bone formed around the implant was maintained at 4 weeks (32.7 microns ± 4.6 vs. 22.6 microns ± 4.0). These results demonstrate the feasibility of developing peptide coated biomaterials designed to elicit a host response at the cell receptor level.

Cells recognize and interact with the extracellular matrix (ECM) through heterodimeric receptors known as integrins. The objective of our work is to immobilize integrin-stimulating peptides to bone-contacting implants in order to control cellular activity and response.We have previously demonstrated that cysteine (C) containing peptides self-assemble onto gold-coated substrates. Investigations have focused on the RGD (Arg-Gly-Asp) peptide sequence since it is found in several bone ECM proteins. Gold was first coated onto glass coverslips by evaporation and the peptide was applied in a 0.22 mM solution. Contact angle and surface plasmon resonance verified RGDC peptide attachment and formation of a monolayer.Rat calvarial osteoblasts isolated from six-day-old rat pups were used from passages one to three. Cell attachment at 20 minutes is 100% greater on RGDC than on CG (control peptides) or plain gold surfaces. Cells on RGDC also stain positively for vinculin, a protein which is present in focal adhesions (functional structures into which integrins assemble) whereas surfaces without integrin stimulating peptides do not. Scanning electron micrographs show cells to be more spread and have more processes at 20 minutes, 1, 3, and 24 hours on RGDC. Live video images of these surfaces from zero to three hours after plating confirmed earlier and greater cell spreading on RGDC.Ongoing in vitro experiments are investigating the long-term response of osteoblasts to RGDC and other immobilized peptides in terms of differentiation, matrix production, and integrin expression.