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In Situ "Humanization" of Porcine Bioprostheses: Demonstration of Tendon Bioprostheses Conversion into Human ACL and Possible Implications for Heart Valve Bioprostheses.

ABSTRACT: This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as "humanization". Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), replacing torn anterior-cruciate-ligament (ACL) in patients. In addition to its possible use in orthopedic surgery, it is suggested that this humanization method should be studied as a possible mechanism for converting implanted porcine bioprosthetic heart-valves (BHV) into viable tissue valves in young patients. Presently, these patients are only implanted with mechanical heart-valves, which require constant anticoagulation therapy. The processing of porcine bioprostheses, which enables humanization, includes elimination of ?-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of ?-gal epitopes prevents subsequent accelerated destruction of implanted tissues by the natural anti-Gal antibody, whereas the partial crosslinking by glutaraldehyde molecules results in their function as "speed bumps" that slow the infiltration of macrophages. Anti-non gal antibodies produced against porcine antigens in implanted bioprostheses recruit macrophages, which infiltrate at a pace that enables slow degradation of the porcine tissue, neo-vascularization, and infiltration of fibroblasts. These fibroblasts align with the porcine collagen-fibers scaffold, secrete their collagen-fibers and other extracellular-matrix (ECM) components, and gradually replace porcine tissues degraded by macrophages with autologous functional viable tissue. Porcine BTB implanted in patients completes humanization into autologous ACL within ~2 years. The similarities in cells and ECM comprising heart-valves and tendons, raises the possibility that porcine BHV undergoing a similar processing, may also undergo humanization, resulting in formation of an autologous, viable, permanently functional, non-calcifying heart-valves.

SUBMITTER: Galili U

PROVIDER: S-EPMC7826727 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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In Situ "Humanization" of Porcine Bioprostheses: Demonstration of Tendon Bioprostheses Conversion into Human ACL and Possible Implications for Heart Valve Bioprostheses.

Galili Uri U Stone Kevin R KR

Bioengineering (Basel, Switzerland) 20210112 1

This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as "humanization". Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), ...[more]

PMID: 33445522

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Project description:The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding.We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79).Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

Project description:Background Transcatheter aortic valve replacement with supra-annular transcatheter heart valves has been adopted in patients with degenerated surgical aortic valves. The next generation self-expanding Evolut PRO valve has not been evaluated in patients with surgical valve failure. Methods and Results Patients undergoing transcatheter aortic valve replacement in degenerated surgical aortic valve procedures using the Evolut R or Evolut PRO transcatheter heart valves in the Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Therapy Registry between April 2015 and June 2019 were evaluated. Transcatheter valve performance was evaluated by clinical site echocardiography. In-hospital, 30-day, and 1-year clinical outcomes were based on the Society of Thoracic Surgeons-American College of Cardiology-Transcatheter Valve Therapy registry definitions. Transcatheter aortic valve replacement in degenerated surgical aortic valve was performed in 5897 patients (5061 [85.8%] patients received the Evolut R valve and 836 [14.2%] received the Evolut PRO valve). Thirty-day transcatheter heart valves hemodynamic performance was excellent in both groups (mean gradient: Evolut PRO: 13.8±7.5 mm Hg; Evolut R: 14.5±8.1 mm Hg), while paravalvular regurgitation was significantly different between valve types (P=0.02). Clinical events were low at 30 days (Evolut PRO: for the all-cause mortality, 2.8%, any stroke was 1.8%, new pacemaker implantation, 3.0%: Evolut R:all-cause mortality, 2.5%, any stroke was 2.2%, new pacemaker implantation, 5.3%) and 1 year (Evolut PRO: all-cause mortality, 9.2%; any stroke, 3.1%; Evolut R: all-cause mortality, 9.8%; any stroke, 2.9%). Conclusions Transcatheter aortic valve replacement in degenerated surgical aortic valve with self-expandable supra-annular transcatheter heart valves is associated with excellent clinical outcomes and valve hemodynamics. Additional reductions in residual paravalvular regurgitation were obtained with the next generation Evolut PRO.

Dataset Information

In Situ "Humanization" of Porcine Bioprostheses: Demonstration of Tendon Bioprostheses Conversion into Human ACL and Possible Implications for Heart Valve Bioprostheses.

Publications

In Situ "Humanization" of Porcine Bioprostheses: Demonstration of Tendon Bioprostheses Conversion into Human ACL and Possible Implications for Heart Valve Bioprostheses.

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