Augmentation of Rotator Cuff Tendon-Bone Healing using Demineralised Bone Matrix and Mesenchymal Stem Cells

BACKGROUND: The results of surgery for tears of the rotator cuff are variable, with failure occurring in up to 94% of cases. Demineralised bone matrix (DBM) consists of a collagen scaffold containing multiple growth factors and has been used successfully to improve tendon-bone healing. By combining DBM with stem cells its effects may be enhanced given that many of the growth factors it contains are able to direct stem cell differentiation down tenogenic, chondrogenic, and osteogenic lineages. These cell lines produce elements essential to the formation of a naturally graded enthesis. AIM: To investigate the effect of DBM on regeneration of the tendon-bone interface, and whether its function can be enhanced by mesenchymal stem cells (MSCs). HYPOTHESIS: DBM will improve tendon-bone healing in an enthesis defect model, and its effect may be further enhanced by the incorporation of MSCs. METHODS: The following experiments were undertaken in order to investigate the hypothesis: 1. Tensile testing of allogenic and xenogenic cortical/cancellous DBM. 2. Evaluating the effect of allogenic and xenogenic DBM, incorporated with MSCs, on regeneration of the enthesis in a large animal model of severe tendon retraction. 3. Development of a chronic rotator cuff tear model. 4. Investigation of tendon-bone healing using DBM in a chronic rotator cuff tear model. 5. Investigation of tendon-bone healing using DBM and MSCs in a chronic rotator cuff tear model. RESULTS: Allogenic cortical DBM possessed the greatest tensile strength and was used in vivo to examine tendon-bone healing complicated by retraction. In this, DBM regenerated a direct enthesis characterised by fibrocartilage. A similar effect was noted in a chronic rotator cuff tear model with no additional effect conferred by the stem cells. CONCLUSION: This thesis has shown that DBM can regenerate a fibrocartilaginous enthesis in models of tendon retraction and chronic rotator cuff degeneration.