Demineralized Bone Matrix to Augment Tendon-Bone Healing: A Systematic Review

Abstract

Background:Following injury to the rotator cuff and anterior cruciate ligament, a direct enthesis is not regenerated, and healing occurs with biomechanically inferior fibrous tissue. Demineralized bone matrix (DBM) is a collagen scaffold that contains growth factors and is a promising biological material for tendon and ligament repair because it can regenerate a direct fibrocartilaginous insertion via endochondral ossification.Purpose:To provide a comprehensive review of the literature investigating the use of DBM to augment tendon-bone healing in tendon repair and anterior cruciate ligament reconstruction (ACLR).Study Design:Systematic review.Methods:Electronic databases (MEDLINE and EMBASE) were searched for preclinical and clinical studies that evaluated the use of DBM in tendon repair and ACLR. Search terms included the following: (“demineralized bone matrix” OR “demineralized cortical bone”) AND (“tissue scaffold” OR “tissue engineering” OR “ligament” OR “tendon” OR “anterior cruciate ligament” OR “rotator cuff”). Peer-reviewed articles written in English were included, and no date restriction was applied (searches performed February 10, 2017). Methodological quality was assessed with peer-reviewed scoring criteria.Results:The search strategy identified 339 articles. After removal of duplicates and screening according to inclusion criteria, 8 studies were included for full review (tendon repair, n = 4; ACLR, n = 4). No human clinical studies were identified. All 8 studies were preclinical animal studies with good methodological quality. Five studies compared DBM augmentation with non-DBM controls, of which 4 (80%) reported positive findings in terms of histological and biomechanical outcomes.Conclusion:Preclinical evidence indicates that DBM can improve tendon-bone healing, although clinical studies are lacking. A range of animal models of tendon repair and ACLR showed that DBM can re-create a direct fibrocartilaginous enthesis, although the animal models are not without limitations. Before clinical trials are justified, research is required that determines the best source of DBM (allogenic vs xenogenic) and the best form of DBM (demineralized cortical bone vs DBM paste) to be used in them.

Are orthobiologics the next chapter in clinical orthopedics? A literature review

“…Orthobiologics have been suggested to enhance healing. A recent review by Hexter et al [52] on the use of DBM to induce tendon-bone healing via enchondral ossification, similar to original enthesis, commented that available data on the topic relies on animal studies. Their conclusion was that although DBM shows potential in animal studies, in order to achieve significant improvements in enthesis healing, combinations of orthobiologics require further investigation.…”

Anterior Cruciate Ligament Reconstruction Using a Ribbon-Like Graft With a C-Shaped Tibial Bone Tunnel

“…Their size and number are positively correlated with the graft pull-out strength. 17 Revascularization only starts after 4 weeks, progressing from the periphery of the graft to the entire diameter. 18 As the contact area of a flat ACL graft is about 3 times greater in relation to its volume compared with a round one, the formation of Sharpey-like fibers as well as the vascularization can take place on an increased area and the distance to the central part of the graft is still limited.…”

Concentrated Bone Marrow Aspirate and Subacromial Bursa-Derived Cells Demonstrate Similar Cellular Adhesion and Proliferation Potential on Demineralized Bone Matrix Scaffolds for Biologic Augmentation of Rotator Cuff Repair

“…Despite these improvements in biologic therapies, extracellular matrix of specific scaffolds is still required to sufficiently deliver and retain applied MSCs to the targeted zone of repaired tissue (12). As artificial scaffolds require biocompatibility in order to ensure retaining the seeded MSCs and mimic natural properties, repair augmentation using demineralized bone matrix (DBM) scaffolds has recently emerged (12)(13)(14)(15)(16). DBM scaffolds are a composite of collagen, several growth factors, along with calcium phosphate.…”

“…DBM scaffolds are a composite of collagen, several growth factors, along with calcium phosphate. Its spongy structure allows for flexibility in the hydrated state, while maintaining an osteoinductive potential (12,13,16). In animal models, DBM has been shown to improve tendon-bone healing and to restore bone mineral density at the enthesis, highlighting its potential role as an augment in rotator cuff healing (14)(15)(16).…”

“…Its spongy structure allows for flexibility in the hydrated state, while maintaining an osteoinductive potential (12,13,16). In animal models, DBM has been shown to improve tendon-bone healing and to restore bone mineral density at the enthesis, highlighting its potential role as an augment in rotator cuff healing (14)(15)(16). In addition, Hoberman et al demonstrated that DBM scaffolds are very potent in retaining applied cells, with bone marrow-derived MSCs (bMSCs) having superior adhesion and proliferation potential on DBM when compared to normal human tendon (12).…”