Prevention of bioprosthetic heart valve tissue calcification by charge modification: Effects of protamine binding by formaldehyde3

摘要: Calcification is the principal cause of clinical failure bioprosthetic heart valves (BHV). occurs through an interaction host and implant factors, mainly younger age glutaraldehyde pretreatment, respectively. The hypothesis this work was that impaired balance between positively negatively charged amino acids, due to reaction with Lys Hyl tissue-collagen residues, expose affinity sites Ca++. We further hypothesized regardless cause(s) BHV calcification, positive charge modification tissues will prevent their propensity calcify. Modification tissue obtained by covalently binding protamine sulfate, a polybasic peptide, via formaldehyde subsequent crosslinking. Protamine-bound exhibited stability properties (shrinkage temperature resistance collagenase digestion) similar tissue. Protamine-treated less permeable Ca++, reduced staining observed dyes, indicating presence functional groups in modified Significant prevention calcification p-bound comparison tissue, 30.9 109 micrograms/mg calcium, respectively, after 30 days subdermal implants rats. procedure resulted stable, covalent links approximately 10% w/w undiminished anticalcification properties, even 1 year storage. results support our hypotheses, orthotopical valve replacements are required order completely evaluate treatment efficacy biocompatibility.