Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits
Autor: | Elifho Obopilwe, Paulos Y. Mengsteab, Ho-Man Kan, Takayoshi Otsuka, Anthony T. Vella, Lakshmi S. Nair, Cato T. Laurencin, Aneesah McClinton, Shiv Shah, Nikoo Saveh Shemshaki |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Anterior cruciate ligament Polyesters Bioengineering 02 engineering and technology Osseointegration Extracellular matrix 03 medical and health sciences Bone marrow aspirate medicine Animals Regeneration Multidisciplinary Anterior Cruciate Ligament Reconstruction Tissue Scaffolds Chemistry Guided Tissue Regeneration Polyethylene Terephthalates Regeneration (biology) 021001 nanoscience & nanotechnology musculoskeletal system Tendon 030104 developmental biology medicine.anatomical_structure surgical procedures operative Physical Sciences Rabbit model Intercellular Signaling Peptides and Proteins Rabbits 0210 nano-technology Disease transmission Biomedical engineering Stem Cell Transplantation |
Zdroj: | Proc Natl Acad Sci U S A |
Popis: | The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix. |
Databáze: | OpenAIRE |
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