Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits

Abstract

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.

Adipose tissue is a critical regulator of osteoarthritis

“…However, increasing evidence is mounting that changes in biomechanical loading due to increased body mass do not account for the severity of obesity-induced knee OA (1)(2)(3)(4)(5)(6)(7)(8)(9). These observations suggest that other factors related to the presence of adipose tissue and adipose tissue-derived cytokines-termed adipokines-play critical roles in this process and other musculoskeletal conditions (1,2,6,7,10). As there are presently no disease-modifying OA drugs available, direct evidence linking adipose tissue and cartilage health could provide important mechanistic insight into the natural history of OA and obesity and therefore guide the development and translation of novel OA therapeutic strategies designed to preserve joint health.…”

Multivalent network modifier upregulates bioactivity of multispecies biofilm-resistant polyalkenoate cement

“…The critical pH for the dental hard tissues is believed to be at 5.5, below which the organic matrix begins to break and initiate demineralization. Similarly, for the deeper tissues at the periosteal level, slight pH changes can affect the healing and mineralization by affecting the cell activity [ 39 ]. We tested the buffering capacity (in lactic acid: pH = 4.0) of the Control against the zPACs in triplicate and observed that zPAC had a more steady change in pH.…”

Control of mesenchymal cell fate via application of FGF-8b in vitro

“…The main actor in the progression of osteoarthritis is controversial, however a greater appreciation of the role adipose tissue (infrapatellar fat pad) plays in promoting osteoarthritis has recently garnered more interest ( Collins et al, 2021 ; Greif et al, 2020 ). Moreover, the combinatorial application of FGF-2 and FGF-8 in the knee joint was recently found to suppress adipokine secretion and demonstrated a decreased inflammatory profile ( Mengsteab et al, 2020 ). Evidence has begun to reveal that adipose tissue promotes inflammation within the knee, which leads to cartilage degeneration.…”