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Creators/Authors contains: "Petrovic, Mark"

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  1. Abstract

    The utility of bioprosthetic heart valves (BHVs) is limited to certain patient populations because of their poor durability compared to mechanical prosthetic valves. Histological analysis of failed porcine BHVs suggests that degeneration of the tissue extracellular matrix (ECM), specifically the loss of proteoglycans and their glycosaminoglycans (GAGs), may lead to impaired mechanical performance, resulting in nucleation and propagation of tears and ultimately failure of the prosthetic. Several strategies have been proposed to address this deterioration, including novel chemical fixatives to stabilize ECM constituents and incorporation of small molecule inhibitors of catabolic enzymes implicated in the degeneration of the BHV ECM. Here, biomimetic proteoglycans (BPGs) were introduced into porcine aortic valves ex vivo and were shown to distribute throughout the valve leaflets. Incorporation of BPGs into the heart valve leaflet increased tissue overall GAG content. The presence of BPGs also significantly increased the micromodulus of the spongiosa layer within the BHV without compromising the chemical fixation process used to sterilize and strengthen the tissue prior to implantation. These findings suggest that a targeted approach for molecularly engineering valve leaflet ECM through the use of BPGs may be a viable way to improve the mechanical behavior and potential durability of BHVs.

     
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  2. Abstract

    Block copolymers (BCPs) are of growing interest because of their extensive utility in tissue engineering, particularly in biomimetic approaches where multifunctionality is critical. We synthesized polycaprolactone‐polyacrylic acid (PCL‐b‐PAA) BCP and crystallized it onto PCL nanofibers, making BCP nanofiber shish kebab (BCP NFSK) structures. When mineralized in 2× simulated body fluid, BCP NFSK mimic the structure of mineralized collagen fibrils. We hypothesized that the addition of a calcium phosphate layer of graded roughness on the nano‐structure of the nanofiber shish kebabs would enhance preosteoblast alkaline phosphatase (ALP) activity, which has been shown to be a critical component in bone matrix formation. The objectives in the study were to investigate the effect of mineralization on cell proliferation and ALP activity, and to also investigate the effect of BCP NFSK periodicity, a structural feature describing the distance between PCL‐b‐PAA crystals on the nanofiber core, on cell proliferation, and ALP activity. ALP activity of cells cultured on the mineralized BCP NFSK template was significantly higher than the nonmineralized BCP NFSK templates. Interestingly, no statistical difference was observed in ALP activity when the periodic varied, indicating that surface chemistry seemed to play a larger role than the surface roughness.

     
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