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Buchmann, Stefan; Sandmann, Gunther H.; Walz, Lars; Reichel, Thomas; Beitzel, Knut; Wexel, Gabriele; Tian, Weiwei; Battmann, Achim; Vogt, Stephan; Winter, Gerhard; Imhoff, Andreas B. (2015): Growth factor release by vesicular phospholipid gels: in-vitro results and application for rotator cuff repair in a rat model. In: BMC Musculoskeletal Disorders 16:82
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Abstract

Background: Biological augmentation of rotator cuff repair is of growing interest to improve biomechanical properties and prevent re-tearing. But intraoperative single shot growth factor application appears not sufficient to provide healing support in the physiologic growth factor expression peaks. The purpose of this study was to establish a sustained release of granulocyte-colony stimulating factor (G-CSF) from injectable vesicular phospholipid gels (VPGs) in vitro and to examine biocompatibility and influence on histology and biomechanical behavior of G-CSF loaded VPGs in a chronic supraspinatus tear rat model. Methods: G-CSF loaded VPGs were produced by dual asymmetric centrifugation. In vitro the integrity, stability and release rate were analyzed. In vivo supraspinatus tendons of 60 rats were detached and after 3 weeks a transosseous refixation with G-CSF loaded VPGs augmentation (n = 15;control, placebo, 1 and 10 mu g G-CSF/d) was performed. 6 weeks postoperatively the healing site was analyzed histologically (n = 9;H&E by modified MOVIN score/Collagen I/III) and biomechanically (n = 6). Results: In vitro testing revealed stable proteins after centrifugation and a continuous G-CSF release of up to 4 weeks. Placebo VPGs showed histologically no negative side effects on the healing process. Histologically in vivo testing demonstrated significant advantages for G-CSF 1 mu g/d but not for G-CSF 10 mu g/d in Collagen III content (p = 0.035) and a higher Collagen I/III ratio compared to the other groups. Biomechanically G-CSF 1 mu g/d revealed a significant higher load to failure ratio (p = 0.020) compared to control but no significant differences in stiffness. Conclusions: By use of VPGs a continuous growth factor release could be obtained in vitro. The in vivo results demonstrate an improvement of immunohistology and biomechanical properties with a low dose G-CSF application via VPG. The VPG itself was well tolerated and had no negative influence on the healing behavior. Due to the favorable properties (highly adhesive, injectable, biocompatible) VPGs are a very interesting option for biologic augmentation. The study may serve as basis for further research in growth factor application models.