The authors declare that they have no competing interests.
Herewith it is confirmed that all authors read and approved the final manuscript. SB: principle investigator, study design, rat surgeries, data evaluation, writing manuscript. GHS: study design, rat surgeries, drafting manuscript. LW: histology, drafting manuscript, grant acquisition. TR: thesis of TR, rat surgeries, biomechanical study design, statistics. KB: biomechanical testing, rat surgeries, drafting manuscript. GW: vet doctor, rat surgeries, study design, drafting manuscript. WT: development of phospholipid gels, in vitro testing, gel production, drafting manuscript. AB: histology, drafting manuscript. SV: study design, animal study supervision, drafting and final approval manuscript. GW: development of phospholipid gels, in vitro testing, gel production, drafting manuscript. ABI: study design, grant acquisition, drafting and final approval manuscript.
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.
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 μg 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).
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 μg/d but not for G-CSF 10 μg/d in Collagen III content (p = 0.035) and a higher Collagen I/III ratio compared to the other groups. Biomechanically G-CSF 1 μg/d revealed a significant higher load to failure ratio (p = 0.020) compared to control but no significant differences in stiffness.
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.
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- Growth factor release by vesicular phospholipid gels: in-vitro results and application for rotator cuff repair in a rat model
Gunther H Sandmann
Andreas B Imhoff
- BioMed Central
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