Development of Novel Sutureless Balloon Expandable Fetal Heart Valve Device Using Absorbable Polycaprolactone Leaflets.

Congenital heart disease (CHD) accounts for nearly one-third of all congenital defects, and patients often require repeated heart valve replacements throughout their lives, due to failed surgical repairs and lack of durability of bioprosthetic valve implants. This objective of this study is to develop and in vitro test a fetal transcatheter pulmonary valve replacement (FTPVR) using sutureless techniques to attach leaflets, as an option to correct congenital defects such as pulmonary atresia with intact ventricular septum (PA/IVS), in utero. A balloon expandable design was analyzed using computational simulations to identify areas of failure. Five manufactured valves were assembled using the unique sutureless approach and tested in the fetal right heart simulator (FRHS) to evaluate hemodynamic characteristics. Computational simulations showed that the commissural loads on the leaflet material were significantly reduced by changing the attachment techniques. Hemodynamic analysis showed an effective orifice area of 0.08 cm2, a mean transvalvular pressure gradient of 7.52 mmHg, and a regurgitation fraction of 8.42%, calculated over 100 consecutive cardiac cycles. In conclusion, the FTPVR exhibited good hemodynamic characteristics, and studies with biodegradable stent materials are underway.

Design consideration of a novel polymeric transcatheter heart valve through computational modeling.

Transcatheter heart valve replacement is becoming a more routine procedure, and this is further supported by positive outcomes from studies involving low-risk patients. Nevertheless, the lack of long-term transcatheter heart valve (TAV) durability is still one of the primary concerns. As a result, more research has been focused on improving durability through various methods such as valve design, computational modeling, and material selection. Recent advancements in polymeric valve fabrication showed that linear low-density polyethylene (LLDPE) could be used as leaflet material for transcatheter heart valves. In this paper, a parametric study of computational simulations showed stress distribution on the leaflets of LLDPE-TAV under diastolic load, and the results were used to improve the stent design. The in silico experiment also tested the effect of shock absorbers in terms of valve durability. The results demonstrated that altering specific stent angles can significantly lower peak stress on the leaflets (13.8 vs. 6.07 MPa). Implementing two layers of shock absorbers further reduces the stress value to 4.28 MPa. The pinwheeling index was assessed, which seems to correlate with peak stress. Overall, the parametric study and the computational method can be used to analyze and improve valve durability.

Transcatheter Heart Valves: A Biomaterials Perspective.

Heart valve disease is prevalent throughout the world, and the number of heart valve replacements is expected to increase rapidly in the coming years. Transcatheter heart valve replacement (THVR) provides a safe and minimally invasive means for heart valve replacement in high-risk patients. The latest clinical data demonstrates that THVR is a practical solution for low-risk patients. Despite these promising results, there is no long-term (>20 years) durability data on transcatheter heart valves (THVs), raising concerns about material degeneration and long-term performance. This review presents a detailed account of the materials development for THVRs. It provides a brief overview of THVR, the native valve properties, the criteria for an ideal THV, and how these devices are tested. A comprehensive review of materials and their applications in THVR, including how these materials are fabricated, prepared, and assembled into THVs is presented, followed by a discussion of current and future THVR biomaterial trends. The field of THVR is proliferating, and this review serves as a guide for understanding the development of THVs from a materials science and engineering perspective.

Development and Fabrication of Vapor Cross-Linked Hyaluronan-Polyethylene Interpenetrating Polymer Network as a Biomaterial.

Flexible heart valve leaflets made from hyaluronan-enhanced linear low-density polyethylene interpenetrating polymeric network (HA-LLDPE IPN) films have been shown to provide good hemodynamics, but the resulting surfaces were not consistent; therefore, the present work tries to mitigate this problem by developing a vapor cross-linked HA-LLDPE IPN. Herein, the HA-LLDPE fabrication process is studied, and its parameters are varied to assess their effects on the IPN formation. Thermal analysis and gas chromatography-mass spectrometry were used to quantify the effects of different treatment conditions on material properties. Water contact angle goniometry, infrared spectroscopy, and toluidine blue O (TBO) staining were used to characterize the surface of the HA-LLDPE IPN. The results show that a hydrophilic surface is formed on HA-LLDPE, which is indicative of HA. HA surface density data from TBO staining show consistent HA distribution on the surface. The IPN fabrication process does not affect the tensile properties that make LLDPE an attractive material for use in flexible heart valve leaflets. The 28 day in vitro biological assays show HA-LLDPE to be noncytotoxic and resistant to enzymatic degradation. The HA-LLDPE showed less platelet adhesion and caused less platelet activation than the plain LLDPE or tissue culture polystyrene. All of the results indicate that vapor cross-linked HA-LLDPE IPN is a promising material for use as flexible leaflets for heart valve replacements.

Hyaluronan enhancement of expanded polytetrafluoroethylene cardiovascular grafts.

Heart disease continues to be the leading cause of death in the United States. The demand for cardiovascular bypass procedures increases annually. Expanded polytetrafluoroethylene is a popular material for replacement implants, but it does have drawbacks such as high thrombogenicity and low patency, particularly in small diameter grafts. Hyaluronan, a naturally occurring polysaccharide in the human body, is known for its wound healing and anticoagulant properties. In this work, we demonstrate that treating the luminal surface of expanded polytetrafluoroethylene grafts with hyaluronan improves hemocompatibility without notably changing its mechanical properties and without significant cytotoxic effects. Surface characterization such as ATR-FTIR and contact angle goniometry demonstrates that hyaluronan treatment successfully changes the surface chemistry and increases hydrophilicity. Tensile properties such as elastic modulus, tensile strength, yield stress and ultimate strain are unchanged by hyaluronan enhancement. Durability data from flow loop studies demonstrate that hyaluronan is durable on the expanded polytetrafluoroethylene inner lumen. Hemocompatibility tests reveal that hyaluronan-treated expanded polytetrafluoroethylene reduces blood clotting and platelet activation. Together our results indicate that hyaluronan-enhanced expanded polytetrafluoroethylene is a promising candidate material for cardiovascular grafts.

Characterizing the Cytocompatibility of Various Cross-Linking Chemistries for the Production of Biostable Large-Pore Protein Crystal Materials.

With rapidly growing interest in therapeutic macromolecules, targeted drug delivery, and in vivo biosensing comes the need for new nanostructured biomaterials capable of macromolecule storage and metered release that exhibit robust stability and cytocompatibility. One novel possibility for such a material are engineered large-pore protein crystals (LPCs). Here, various chemically stabilized LPC derived biomaterials were generated using three cross-linking agents: glutaraldehyde, oxaldehyde, and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. LPC biostability and in vitro mammalian cytocompatibility was subsequently evaluated and compared to similarly cross-linked tetragonal hen egg white lysozyme crystals. This study demonstrates the ability of various cross-linking chemistries to physically stabilize the molecular structure of LPC materials-increasing their tolerance to challenging conditions while exhibiting minimal cytotoxicity. This approach produces LPC-derived biomaterials with promising utility for diverse applications in biotechnology and nanomedicine.

PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries.

Marrow stromal cells (MSCs) have been suggested as a means to improve healing in tendon overuse injuries (tendinopathy), but optimal delivery methods for these cells have yet to be determined. In this study novel degradable hydrogels based on oligo(poly(ethylene glycol) fumarate) (OPF) and acrylated poly(ethylene glycol)-dithiothreitol (Ac PEG-DTT) with tunable degradation times ranging from a few days to >1 month were synthesized as MSC carriers for tendon overuse injuries. The addition of higher amounts of OPF or higher dithiothreitol (DTT) concentrations resulted in enhanced fold swelling and degradation. Three formulations, including non-degrading, slower degrading (degraded in ∼10 days) and faster degrading (degraded in ∼5 days) hydrogels were selected for studies with MSCs in tendon tissue explants that had been treated with collagenase as a reproducible model of tendinopathy. Quantitative analysis of the resulting histology images indicated that cell delivery from the hydrogels was dependent on the degradation rate, with cells present in the tissue only after hydrogel dissolution. In addition, significantly more cells were found in the tendon after 14 days with the fast degrading (53±19) vs. slow degrading (20±6) hydrogels. Based on these results, OPF/Ac PEG-DTT hydrogels provide a versatile biomaterial platform to control cell delivery and thus better identify dosing regimens required for MSC-based therapies for tendinopathy.