Porcine dermal collagen permanently crosslinked with hexamethylene diisocyanate was investigated for its suitability as a dermal tissue engineering matrix. It was found that the chemically crosslinked collagen had far fewer free lysine groups per collagen molecule than did the uncrosslinked matrix. The ability of the matrix to support human primary fibroblast outgrowth from explants was compared for matrices that had been presoaked in various solutions, including fibroblast media, cysteine and phosphate buffered saline (PBS). It was found that superior cell outgrowth was obtained after soaking with fibroblast media and PBS. The fibroblast attachment properties of the matrix were compared against tissue culture plastic and PET. The collagen matrix showed the least amount of cell retention compared to the other to matrices, however, the general trends were similar for all three scaffolds. Longer term cultures on the collagen showed fibroblasts covering the matrix stacking up on each other and bridging natural hair follicles. However, it was also observed that the fibroblasts were not able to penetrate into the matrix structure. This was believed to result from the chemical crosslinking, as shown by the resistance of the matrix to degradation by collagenases.
Biologic reactivity to orthopedic implant debris is generally the main determinant of long-term clinical performance where released polymeric particles of Ultra-high molecular weight polyethylene (UHMWPE) remain the most prevalent debris generated from metal-on-polymer bearing total joint arthroplasties. Polymeric alternatives to UHMWPE such as polyetherether-ketone (PEEK) may have increased wear resistance but the bioreactivity of PEEK-OPTIMA particles on peri-implant inflammation remains largely uncharacterized. We evaluated human monocyte/macrophage responses (THP-1s and primary human) when challenged by PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles of three particle sizes (0.7 um, 2 um, and 10 um) at a dose of 20 particles-per-cell at 24- and 48-h time points. Macrophage responses were measured using cytotoxicity assays, viability assays, proliferation assays and cytokine analysis (IL-1b, IL-6, IL-8, MCP-1, and TNF-α). In general, there were no significant differences between PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles on macrophage viability or proliferation. However, macrophages demonstrated greater cytotoxicity responses to UHMWPE and X-UHMWPE than to PEEK-OPTIMA at 24 and 48 h, where 0.7 μm-UHMWPE particles produced the highest amount of cytotoxicity. Particles of X-UHMWPE more than PEEK-OPTIMA and UHMWPE induced IL-1β, IL-6, MCP-1, and TNF-α at 24 h, p < 0.05 (no significant differences at 48 h). On average, cytokine production was more adversely affected by larger 10 μm particles than by 0.7 and 2 μm sized particles. While limitations of in vitro analysis apply to this study, PEEK-OPTIMA particles were more biocompatible than UHMWPE particles, in that they induced less inflammatory cytokine responses and thus, in part, demonstrates that PEEK-OPTIMA implant debris does not represent an increased inflammatory risk over that of UHMWPE.
Previous observations of cytocompatibility and calcification on the PEEK biomaterial could be carried through to this new porous form of the PEEK biomaterial. This helps porous PEEK to potentially offer more design options for implant devices requiring reduced modulus and/or increased tissue ingrowth aspects at the surface.
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