scholarly journals In Situ “Humanization” of Porcine Bioprostheses: Demonstration of Tendon Bioprostheses Conversion into Human ACL and Possible Implications for Heart Valve Bioprostheses

2021 ◽  
Vol 8 (1) ◽  
pp. 10
Author(s):  
Uri Galili ◽  
Kevin R. Stone
Keyword(s):  
Extracellular Matrix ◽  
Heart Valves ◽  
Cruciate Ligament ◽  
Anticoagulation Therapy ◽  
Young Patients ◽  
Collagen Fibers ◽  
Reconstruction Process ◽  
Bioprosthetic Heart Valves ◽  
Porcine Tissue ◽  
Anterior Cruciate

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 α-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of α-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.

Assessing Physical Activity After ACL Injury: Moving Beyond Return to Sport

2021 ◽  
pp. 194173812110253
Author(s):  
Christopher Kuenze ◽  
Katherine Collins ◽  
Karin Allor Pfeiffer ◽  
Caroline Lisee
Keyword(s):  
Physical Activity ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Young Patients ◽  
Return To Sport ◽  
Acl Injury ◽  
Noncommunicable Diseases ◽  
Successful Recovery ◽  
Patient Reported ◽  
Anterior Cruciate

Context: Return to sport is widely utilized by sports medicine researchers and clinicians as a primary outcome of interest for successful recovery when working with young patients who have undergone anterior cruciate ligament (ACL) reconstruction (ACLR). While return-to-sport outcomes are effective at tracking progress post-ACLR, they are limited because they do not necessarily capture physical activity (PA) engagement, which is important to maintain knee joint health and reduce the risk of noncommunicable diseases. Therefore, there is a critical need (1) to describe current PA participation and measurement recommendations; (2) to appraise common PA measurement approaches, including patient-reported outcomes and device-based methodologies; and (3) to provide clinical recommendations for future evaluation. Evidence Acquisition: Reports of patient-reported or device-based PA in patients with ACL injury were acquired and summarized based on a PubMed search (2000 through July 2020). Search terms included physical activity OR activity AND anterior cruciate ligament OR ACL. Study Design: Clinical review. Level of Evidence: Level 5. Results: We highlight that (1) individuals with ACLR are 2.36 times less likely to meet the US Department of Health and Human Services PA recommendations even when reporting successful return to sport, (2) common patient-reported PA assessments have significant limitations in the data that can be derived, and (3) alternative patient-reported and device-based assessments may provide improved assessment of PA in this patient population. Conclusion: Clinicians and researchers have relied on return to sport status or self-reported PA participation via surveys. These approaches are not consistent with current recommendations for PA assessment and do not allow for comparison with contemporary PA recommendations or guidelines. Return to sport, patient-reported outcome measures, and device-based assessment approaches should be used in complementary manners to comprehensively assess PA participation after ACLR. However, appropriate techniques should be used when assessing PA in adult and adolescent populations.

scholarly journals Ultrastructural pathology of bioprosthetic heart valves with infectious endocarditis

2021 ◽  
Vol 6 (3) ◽  
pp. 25-34
Author(s):  
R. A. Mukhamadiyarov ◽  
I. V. Milto ◽  
A. G. Kutikhin
Keyword(s):  
Extracellular Matrix ◽  
Heart Valves ◽  
Osmium Tetroxide ◽  
Giant Cells ◽  
Uranyl Acetate ◽  
Diglycidyl Ether ◽  
Multinucleated Giant Cells ◽  
Bioprosthetic Heart Valves ◽  
Sputter Coating ◽  
Backscattered Scanning Electron Microscopy

Aim. To study the ultrastructure of mitral bioprosthetic heart valves (BHVs) which failed due to infective endocarditis.Materials and Methods. Here we examined 7 ethylene glycol diglycidyl ether-treated xenopericardial BHVs excised during repeated BHV replacement because of prosthetic endocarditis. After being fixed in formalin and postfixed in osmium tetroxide, BHVs were dehydrated and stained in uranyl acetate with the subsequent embedding into epoxy resin, grinding, polishing, and lead citrate counterstaining. Upon the sputter coating with carbon, we visualised the BHV microanatomy by means of backscattered scanning electron microscopy at 15 kV voltage.Results. The extracellular matrix underwent degradation and disintegration resulting in loosening, fragmentation, and reduction in the electron density of collagen and elastin fibers. We observed a number of recipient cells (macrophages, multinucleated giant cells, neutrophils, endothelial cells and smooth muscle cells) within the BHVs. The highest number of cells was localized on the valve surfaces. The localization of the recipient cells on the ventricular and atrial surfaces was different. The central part of the valves was abundantly populated by macrophages.Conclusion. Prosthetic endocarditis is accompanied by the migration of recipient cells into the BHV structure, which is the consequence of surface and extracellular matrix disintegration.

scholarly journals Anterior Cruciate Ligament Tear Promotes Skeletal Muscle Myostatin Expression, Fibrogenic Cell Expansion, and a Decline in Muscle Quality

2019 ◽  
Vol 47 (6) ◽  
pp. 1385-1395 ◽  
Author(s):  
Bailey D. Peck ◽  
Camille R. Brightwell ◽  
Darren L. Johnson ◽  
Mary Lloyd Ireland ◽  
Brian Noehren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Quadriceps Muscle ◽  
Muscle Quality ◽  
Injured Limb ◽  
Extracellular Matrix Components ◽  
Anterior Cruciate

Background: Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies. Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury. Study Design: Descriptive laboratory study. Methods: After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components. Results: Injured limb skeletal muscle demonstrated elevated myostatin gene ( P < .005) and protein ( P < .0005) expression, which correlated ( R2 = 0.38, P < .05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro ( P < .05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb ( P < .05). The abundance of procollagen 1–expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb ( P < .05). Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury. Clinical Relevance: The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport.

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