Repair of rotator cuff injury in rabbit animal model by in situ implantation of an injectable elastin-like recombinamer and allogeneic mesenchymal stem cells

摘要

Introduction: One of the most common musculoskeletal pathologies is the shoulder pain, the rotator cuff injury affects more than 40% of patients over 60 years and causes disabling pain and loss of shoulder functionality. Despite the recent improvements and advances in the surgery, there remains a failure rate of between 20% and 70%. To obtain the tendon repair augmentation the new treatment strategies are directed to reinforce the mechanical properties and the biological healing capacity by implanting matrices, although the currently in use usually cause inflammatory reaction. To solve this problem, in this study we employed a modified version of an advanced matrix that has been demonstrating high efficiency and biocompatibility as bioactive support in regenerative medicine. It belongs to the family of (ELRs) the Elastin-like recombinamers with high mechanical performance designed as injectable thermogelling systems. The matrix was co-injected with rabbit bone marrow mesenchymal stem cells (rMSCs), under physiological conditions to evaluate the effect of cell therapy on the tendon pathology. Experimental Methods: ELRs were produced by DNA recombinant techniques and E. coli biosynthesis as described elsewhere. Rabbit mesenchymal stem cells (rMSCs) were obtained from rabbit bone marrow and BrdU stained. New Zealand rabbits with critical defect in the infraspinatus tendon were randomly allocated into 3 groups (negative control, treated with ELRs matrix, treated with ELRs matrix and rMSCs). At 10,1,4 and 16 weeks the animals were sacrificed and their tendons removed to perform biomechanical tests and immunohistochemical analysis. Results and Discussion: This study describes the use of injectable thermo-gelling scaffold whose applicability is focused specifically on regenerative medicine. The scaffold generated "in situ" under physiological condition was assayed in combination or not with rMSCs for the forming of an artificial matrix that improved tendon repair capacity. The results at 0,1,4 and 16 weeks were compared with which obtained adding ELR matrix and with the normal healing process the after injury of the infraspinatus tendon in rabbits. Figure 1. Showed the BRdU stained rMSCs and the ELR matrix after 1 month in the rabbit tendon implantation. In this work we observed a stronger and more physiological infraspinatus tendon repair using allogeneic rabbit mesenchymal stem cells in combination with an innovative ELRs thermogelling scaffold. Conclusion: The thermo-gelling property of the ELRs matrix has greatly facilitated the surgical technique as it is easier to handle (for injection), especially when used arthroscopically. The bioactivity and biocompatibility of the matrix enhanced the adhesion and proliferation of the rMSCs embedded in ELR-matrix in vitro. The in vivo tendon suture repair of the infraspinatus tendon has been studied in New Zealand rabbits. The rMSCs showed a high proliferation rate in the ELRs matrix when implanted in the tendons and a reinforced structural was obtained as was proved through the biomechanical, histological and immunohistochemical assays.