Soluble allogenic telocollagen as a direct protein therapeutic: Results of serial injections in a rodent rotator cuff tear model.

Abstract

Hypothesis: Delivery of soluble allogeneic type I telocollagen (allo-telocollagen) will accelerate and improve the healing of damaged tendons. Our hypothesis draws from known mechanochemical properties of type I collagen that direct its incorporation into damaged connective tissue. We further suggest that allo-telocollagen will raise a minimal immunogenic reaction due to homology within species.

Methods: Seventy-eight shoulders (39 Sprague-Dawley rats) had their supraspinatus tendon surgically detached from its footprint on the humerus and repaired (72 shoulders) or left uninjured (6 shoulders). The repaired tissue was treated with an injection of 100 μl of saline, 10 mg/ml allogeneic atelocollagen (allo-atelocollagen), or 10 mg/ml allo-telocollagen at 0-, 1-, and 2-weeks post-surgery. At 30- and 60-days post-surgery, the tendons were assessed by mechanical testing (failure load, failure stress, stiffness, and relaxation) and by semiquantitative histological scoring.

Results: At 30-days post-surgery, the mechanical and histological outcomes were not statistically different. However, at day 60, allo-telocollagen improved the failure strength of the supraspinatus (29.9 ± 4.7 N) relative to saline (20.0 ± 3.5 N; P value <= 0.001) or allo-atelocollagen (23.2 ± 1.5 N; P value = 0.025) treated tendons, and it approached that of uninjured controls (36.9 ± 5.0 N; P value = 0.021). Allo-telocollagen improved the failure stress of the supraspinatus (34.1 ± 9.3 MPa) relative to the saline treated tendons (21.4 ± 6.0 MPa; P value = 0.031; 160% improvement) and was no different than uninjured controls (33.4 ± 9.9 MPa; P value = 0.999) or allo-atelocollagen (32.3 ± 7.4 MPa; P value = 0.977). The stiffness of uninjured controls was far greater than any of injured/treated tendons (>200% stiffer). Histological scoring showed that the allo-telocollagen treated tendons produced better collagen fiber arrangement (1.55 ± 0.17) than saline (2.50 ± 0.29; P value = 0.001) or allo-atelocollagen (2.23 ± 0.28; P value = 0.042) treated tendons and that it did not increase markers of immunogenesis (1.10 ± 0.42) relative to either saline (1.44 ± 0.20; P value = 0.369) or allo-atelocollagen (0.68 ± 0.41; P value = 0.1058).

Conclusions: While all three treatments produced similar results at 30 days, by 60 days, soluble allo-telocollagen clearly separated from the other interventions, yielding better mechanical and histological outcomes in a torn/repaired rotator cuff rat model. Allo-telocollagen treated tendons also approached the failure strength and matched the failure stresses of uninjured control tendons. The data suggest a new use for allo-telocollagen as a deliverable direct protein mechanotherapeutic that can improve both healing quality and speed.