Fixation of Bovine Pericardium-Based Tissue Biomaterial with Irreversible Chemistry Improves Biochemical and Biomechanical Properties

Abstract

Bioprosthetic heart valves (BHVs), derived from glutaraldehyde crosslinked (GLUT) porcine aortic valve leaflets or bovine pericardium (BP), are used to replace defective heart valves. However, valve failure can occur within 12–15 years due to calcification and/or progressive structural degeneration. We present a novel fabrication method that utilizes carbodiimide, neomycin trisulfate, and pentagalloyl glucose crosslinking chemistry (TRI) to better stabilize the extracellular matrix of BP. We demonstrate that TRI-treated BP is more compliant than GLUT-treated BP. GLUT-treated BP exhibited permanent geometric deformation and complete alteration of apparent mechanical properties when subjected to induced static strain. TRI BP, on the other hand, did not exhibit such permanent geometric deformations or significant alterations of apparent mechanical properties. TRI BP also exhibited better resistance to enzymatic degradation in vitro and calcification in vivo when implanted subcutaneously in juvenile rats for up to 30 days.

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

“…70,88 The aforementioned advantages of PGG have paved the path for its use in tissue engineering studies of valves, development of vascular grafts, and numerous other potential therapeutic applications. 32,33,35,39,47,88,119,120,129,154,156,167,168,170,171 In this review, we critically evaluate recent work relevant to drug-delivery and translation-related applications of PGG.…”

Calcification of Biomaterials and Diseased States

“…Little to no calcification was found on any of the leaflets. The study showed the potential benefits of using this cross-linking method to prevent or delay calcification in implants, though further data should be collected (Figure 3) [5]. Treating the biomaterial with POSS to form POSS-PCU changes existing receptors so that free calcium ions are no longer able to bind, preventing deposition and mineralization [5].…”

“…Several crosslinking methods, specifically crosslinking with glutaraldehyde, provide strength by preventing degradation, but the elastin in the ECM is not protected. This leads to stiffness, tears, and deformations in the surface of the material, a condition known as "permanent set" [5]. A modified form of crosslinking involving treating the surface of biomaterial implants with pentagalloyl glucose does not cause damage to collagen or surface deformations.…”

“…Vascular calcification is also seen to increase in patients on dialysis, due to serum being stripped of natural inhibitors of mineralization [4]. Valve implants, coronary stents, and balloon angioplasty are all affected by mineralization due to immune response of biomaterials used, calcium affinity, or even elastin/collagen injury post-implantation [5]. The consequence of this calcification is often associated with implant failure and stiffness of tissue.…”

Tissue Engineering—Bridging the Gap

“…The challenges in translating the data from pre-clinical and clinical pilot trials that will ultimately be faced by all tissue engineering projects are also reviewed [4]. The experimental studies in this issue address a variety of topics within the heart valve field including two papers on the development of decellularised valves [5,6], the chemical fixation of bovine pericardium and the assessment of a new transcatheter heart valve [7,8]. Within the vascular field, there are two papers, the first addresses the use of an in vivo approach that utilises the host reaction to an implanted biomaterial for the generation of completely autologous tissues, while the second examines the use of intravascular echo as a tool to evaluate the changes within tissue-engineered valves implanted into sheep [9,10].…”