Soluble allogeneic 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 as a result of 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 postsurgery. At 30 and 60 days postsurgery, the tendons were assessed by mechanical testing (failure load, failure stress, stiffness, and relaxation) and by semiquantitative histologic scoring.

Results

At 30 days postsurgery, the mechanical and histologic 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 < .001) or allo-atelocollagen (23.2 ± 1.5 N, P = .025) treated tendons, and it approached that of uninjured controls (36.9 ± 5.0 N, P = .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 = .031, 160% improvement) and was no different than uninjured controls (33.4 ± 9.9 MPa, P = .999) or allo-atelocollagen (32.3 ± 7.4 MPa, P = .977). The stiffness of uninjured controls was far greater than any of injured or treated tendons (>200% stiffer). Histologic scoring showed that the allo-telocollagen–treated tendons produced better collagen fiber arrangement (1.55 ± 0.17) than saline (2.50 ± 0.29, P = .001) or allo-atelocollagen (2.23 ± 0.28, P = .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 = .369) or allo-atelocollagen (0.68 ± 0.41, P = .1058).

Conclusions

Although all 3 treatments produced similar results at 30 days, by 60 days, soluble allo-telocollagen clearly separated from the other interventions, yielding better mechanical and histologic outcomes in a torn or 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.