Osteoinductive Bone Morphogenic Protein, Collagen Scaffold, Calcium Phosphate Cement, and Magnesium-Based Fixation Enhance Anterior Cruciate Ligament Tendon Graft to Bone Healing In Animal Models: A Systematic Review.

Purpose: To perform a systematic literature review to analyze the results of the in vivo animal models and strategies that use osteoinductive materials to enhance the tendon graft-bone interface for anterior cruciate ligament reconstruction (ACLR).

Methods: Following the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines, the PubMed, Embase, and Web of Science databases were searched. The inclusion criteria were studies of in vivo animal models of ACLR using a material to enhance tendon graft-bone interface healing and reporting at least the histologic results at the interface, along with radiologic and biomechanical data. Studies without control group or with another tendon-bone healing model were excluded. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments 1guidelines.

Results: Twenty-seven studies met the inclusion criteria. Rabbit was the main animal model of ACLR, along with sheep and dog models. ACLR procedures varied widely between studies.. The main promising strategies and materials were wrapping the material around the graft, with a collagen scaffold loaded with an osteoinductive molecule (mostly bone morphogenetic proteins). The second strategy consisted of injecting the material at the tendon-bone interface; calcium phosphate cement or a derivative were the most used materials. Finally, using osteoinductive fixation devices was the third strategy; magnesium-based interference screws seemed to show most favorable results.

Conclusions: The studies retained had major methodologic flaws that limit the scope of these conclusions. However, based on histologic, biomechanical, and radiologic analyses, the most promising materials were a collagen scaffold loaded with an osteoinductive molecule and wrapped around the graft, calcium phosphate cement injected in the bone tunnel, and a magnesium-based fixation device.

Clinical Relevance: In vivo animal models have identified several promising strategies and materials to optimize the tendon-bone interface after ACLR, but standardized and reproducible assessments are needed before these strategies can be adopted clinically.