Calcification resistance, biostability, and low immunogenic potential of porcine heart valves modified by dye-mediated photooxidation

Abstract

The calcification potential, biostability, and immunogenic response of materials intended for long-term in vivo use, such as in heart-valve bioprostheses, are essential components of device performance. Here we explore these properties in photooxidized porcine heart valves. To study immunological sensitization, we injected tissue extracts intradermally into guinea pigs. Test and control animals received a challenge patch of the appropriate extract and were scored for dermal reactions. Neither cottonseed oil nor sodium chloride extracts of photooxidized heart-valve tissues caused any dermal inflammatory response. After implantation in the rat subcutaneous model for 90 days, the calcium content of 48-h-treated photooxidized cusp tissue [0.04 +/- 0.00 mg/g wet weight (gww)] was comparable to that of unimplanted control tissues (usually <1 mg/gww) and much lower than that of glutaraldehyde-treated controls (71 +/- 15 mg/gww). The porcine aortic wall calcium content (49 +/- 31 mg/gww) was comparable to that of glutaraldehyde-treated controls (59 +/- 8 mg/gww). Histologically, a time-dependent decrease in inflammation and vascularization with increasing photooxidation time was noted in the rat model along with an increase in the stability and organization of collagen bundles. In summary, porcine valve tissues treated by dye-mediated photooxidation were resistant to calcification, were biostable, and demonstrated a low immunogenic response, indicating potential for use in heart-valve bioprostheses.

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right‐side heart implantation

“…Photooxidatively crosslinked biomaterials resisted cell‐ and collagen‐associated calcification 12, 27. In this study, H&E and immunohistochemical staining showed acellularization for photooxidized BJVCs in the inner layer regions of the walls and all layers of valves at 1‐year implantation, which is similar to the performance of homografts in long‐term implantation 28.…”

Cross‐linking of extruded collagen fibers—A biomimetic three‐dimensional scaffold for tissue engineering applications

“…Furthermore, the physical methods although they are more biocompatible than the chemical approaches since they involve the modification and cross‐link formation of the existing matrix components and no‐external chemical is used, result in materials with little added matrix complexity and so there is no significant rise in the thermal stability compared with untreated tissue 3, 115–118. Photo‐oxidation, for example, yields a material with a relatively small shrinkage temperature change, having a shrinkage temperature similar to the untreated material, which suggests that the tissue and/or scaffold behaves like the original and that the cross‐links did not influence the tissue/scaffold character 115, 119, 120…”

Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors

“…[10,17,18] Photooxidized materials have been used clinically in cardiac surgery, and, to the best of our knowledge, with the graft material tested as a whole and not its potential constituents. [11-16]…”

“…Photooxidation is a light-mediated process that results in the cross-linking of collagen fibers. The result is a material that is relatively non-immunogenic and resistant to chemical and enzymatic degradation, while maintaining the mechanical properties of the tissue, as demonstrated with bovine [7-10] and porcine [11,12] tissue. The photooxidized cartilage has been shown to have no viable chondrocytes after treatment.…”