Platelet-Rich Fibrin–Augmented Gap-Bridging Strategy in Rabbit Anterior Cruciate Ligament Repair

Abstract

Background: We assessed the efficacy of a novel platelet-rich fibrin (PRF)–augmented repair strategy for promoting biological healing of an anterior cruciate ligament (ACL) midsubstance tear in a rabbit model. The biological gap-bridging effect of a PRF scaffold alone or in combination with rabbit ligamentocytes on primary ACL healing was evaluated both in vitro and in vivo. Hypothesis: A PRF matrix can be implanted as a provisional fibrin-platelet bridging scaffold at an ACL defect to facilitate functional healing. Study Design: Controlled laboratory study. Methods: The biological effects of PRF on primary rabbit ligamentocyte proliferation, tenogenic differentiation, migration, and tendon-specific matrix production were investigated for treatment of cells with PRF-conditioned medium (PRFM). Three-dimensional (3D) lyophilized PRF (LPRF)–cell composite was fabricated by culturing ligamentocytes on an LPRF patch for 14 days. Cell-scaffold interactions were investigated under a scanning electron microscope and through histological analysis. An ACL midsubstance tear model was established in 3 rabbit groups: a ruptured ACL was treated with isolated suture repair in group A, whereas the primary repair was augmented with LPRF and LPRF-cell composite to bridge the gap between ruptured ends of ligaments in groups B and C, respectively. Outcomes—gross appearance, magnetic resonance imaging, and histological analysis—were evaluated in postoperative weeks 8 and 12. Results: PRFM promoted cultured ligamentocyte proliferation, migration, and expression of tenogenic genes (type I and III collagen and tenascin). PRF was noted to upregulate cell tenogenic differentiation in terms of matrix production. In the 3D culture, viable cells formed layers at high density on the LPRF scaffold surface, with notable cell ingrowth and abundant collagenous matrix depositions. Moreover, ACL repair tissue and less articular cartilage damage were observed in knee joints in groups B and C, implying the existence of a chondroprotective phenomenon associated with PRF-augmented treatment. Conclusion: Our PRF-augmented strategy can facilitate the formation of stable repair tissue and thus provide gap-bridging in ACL repair. Clinical Relevance: From the translational viewpoint, effective primary repair of the ACL may enable considerable advancement in therapeutic strategy for ACL injuries, particularly allowing for proprioception retention and thus improved physiological joint kinematics.

Current Progress of Platelet-Rich Derivatives in Cartilage and Joint Repairs

“…Two systematic reviews and meta-analyses examining treatment with PRP reported that lateral epicondylitis, commonly known as tennis elbow, improves pain and function more effectively than corticosteroid injections in the intermediate term (12–26 weeks) [ 96 ] and for long-term follow-up (24 weeks post-treatment) [ 97 ]. Another systematic review demonstrated that PRP injection did not significantly reduce the pain intensity in chronic greater trochanteric pain syndrome compared with placebo injection (saline) [ 98 ], and a randomized, double-blind, controlled trial showed that PRP could achieve greater clinical improvements at 12 weeks than corticosteroid injection [ 99 ]. A systematic review of 34 randomized trials revealed that the use of PRP injections has a low risk of harm and is beneficial for long-term outcomes (≥12 months).…”

Platelet-Rich Fibrin–Augmented Gap-Bridging Strategy in Rabbit Anterior Cruciate Ligament Repair: Letter to the Editor

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We are writing to request a better explanation of the method of venipuncture to produce platelet-rich fibrin (PRF) in rabbits in the article recently published by Weng et al 2 Additionally, the authors of the present letter would like to highlight the use of rabbits for this captivating study not only because of the use of the surgical model but also because rabbits are considered one of the best species for examining platelets. 1 Different sites can be used for venipuncture in rabbits, such as the ear, jugular vein, and heart.

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“…For the second part, in fact, we have done very thorough PRF characterization in our previous studies using the rabbit animal model, particularly on the cytokine content and its release kinetics from the PRF scaffold. 2,3 The concentrations of 5 different kinds of growth factors released from PRF, PDFG-AA, PDFG-BB, FGF-2, TGF-b, and IGF-1, were measured at different time points (1 hour, 6 hours, 12 hours, 24 hours, 72 hours, and 6 days).…”

“…In their article, Weng et al 2 should clarify these aspects because they go beyond an experimental surgical assessment. Moreover, as a translational study, a comparison with human beings in the Discussion section would help readers understand the relevance of the study's findings.…”

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing

“…Endogenous healing contributed to the recovery of tendon biomechanics and motor function. , Regrettably, tendons exhibit restricted intrinsic healing capabilities due to low cell density and a blood supply. The rupture of the epitendineum and inadequate blood supply impede the formation of Fb hematoma, leading to reduced metabolic activity and prolonged inflammatory reactions, , ultimately resulting in adhesion. ,,− Strategies to enhance endogenous healing have been attempted, ,, including the use of Fb clots as temporary scaffolds to trigger the healing cascade reaction, regulate inflammation, and restore early blood supply. − In our prior study, Fb-loaded nanofibers were found to effectively promote endogenous healing of tendons.…”