Injectable Fibrocartilage-Forming Cores Enhance Bone-Tendon Healing in a Rat Rotator Cuff Model

BACKGROUND: After surgical repair of rotator cuff (RC) tears, the torn tendon heals unsatisfactorily to the greater tuberosity owing to limited regeneration of the bone-tendon (BT) insertion. This situation motivates the need for new interventions to enhance BT healing in the RC repair site. PURPOSE: To develop injectable fibrocartilage-forming cores by tethering fibroblast growth factor 18 (FGF18) on acellular fibrocartilage matrix microparticles (AFM-MPs) and evaluate their efficacy on BT healing. STUDY DESIGN: Controlled laboratory study. METHODS: We harvested normal fibrocartilage tissue from the porcine RC insertion, after which it was decellularized and then micronized for fabricating AFM-MPs. The collagen-binding domain was fused into the N-terminus of FGF18 to synthesize recombinant FGF18 (CBD-FGF18), which was tethered to the collagen fibers of AFM-MPs to prepare the injectable fibrocartilage-forming cores (CBD-FGF18@AFM-MPs). After examining the influence of the CBD-FGF18@AFM-MPs on the viability and chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro, we determined the function of the CBD-FGF18@AFM-MPs on BT healing in a rat RC tear model. A total of 80 Sprague-Dawley rats with RC injuries were randomly assigned to 4 supplemental treatments during RC repair: saline injection (control group), AFM-MPs injection, natural FGF18@AFM-MPs injection, and CBD-FGF18@AFM-MPs injection. At 4 and 8 weeks postoperatively, the harvested RC specimens were evaluated via micro-computed tomography, histologic staining, and mechanical testing. RESULTS: In vitro, the CBD-FGF18@AFM-MPs were highly biomimetic, suitable for cell growth and proliferation, and superior in stimulating chondrogenesis. In vivo micro-computed tomography results showed that the CBD-FGF18@AFM-MPs group had significantly more new bone formation and better bone remodeling than the other 3 groups. Histologically, at 4 and 8 weeks postoperatively, the CBD-FGF18@AFM-MPs group had the best continuity of the BT insertion with regular collagen alignment and extensive fibrocartilage regeneration. Importantly, at 8 weeks postoperatively, the RC specimens from the CBD-FGF18@AFM-MPs group presented the highest failure load and stiffness. CONCLUSION: The injectable fibrocartilage-forming cores provide a new biological intervention to promote RC healing. CLINICAL RELEVANCE: The injectable fibrocartilage-forming cores may be a new complementary treatment for surgical repair of RC tears.