Effect of recombinant human platelet-derived growth factor-BB-coated sutures on Achilles tendon healing in a rat model: A histological and biomechanical study

Abstract

Purpose: Repairing tendon injuries with recombinant human platelet-derived growth factor-BB has potential for improving surgical outcomes. Augmentation of sutures, a critical component of surgical tendon repair, by coating with growth factors may provide a clinically useful therapeutic device for improving tendon repair. Therefore, the purpose of this study was to (a) coat Vicryl sutures with a defined dose of recombinant human platelet-derived growth factor-BB without additional coating excipients (e.g. gelatin), (b) quantify the recombinant human platelet-derived growth factor-BB released from the suture, and (c) use the recombinant human platelet-derived growth factor-BB-coated sutures to enhance tendon repair in a rat Achilles tendon transection model.

Methods: Vicryl sutures were coated with 0, 0.3, 1.0, and 10.0 mg/mL concentrations of recombinant human platelet-derived growth factor-BB using a dip-coating process. In vitro release was quantified by an enzyme-linked immunosorbent assay. Acutely transected rat Achilles tendons were repaired using one of the four suture groups (n = 12 per group). Four weeks following repair, the tensile biomechanical and histological (i.e. collagen organization and angiogenesis) properties were determined.

Results: A dose-dependent bolus release of recombinant human platelet-derived growth factor-BB occurred within the first hour in vitro, followed by a gradual release over 48 h. There was a significant increase in ultimate tensile strength (p < 0.01) in the two highest recombinant human platelet-derived growth factor-BB dose groups (1.9 ± 0.5 and 2.1 ± 0.5 MPa) relative to controls (1.0 ± 0.2 MPa). The modulus significantly increased (p = 0.031) with the highest recombinant human platelet-derived growth factor-BB dose group (7.2 ± 3.8 MPa) relative to all other groups (control: 3.5 ± 0.9 MPa). No significant differences were identified for the maximum load or stiffness. The histological collagen and angiogenesis scores were comparable in all groups, although there was a trend for improved collagen organization in the recombinant human platelet-derived growth factor-BB-treated groups (p = 0.054).

Conclusions: The results of this study suggest that recombinant human platelet-derived growth factor-BB can be used to reproducibly coat Vicryl sutures and improve remodeling in a rat Achilles tendon transection model by significantly decreasing the resulting cross-sectional area, thus improving the material properties of the repaired tendon.

Keywords: biomechanics; histology; recombinant human platelet-derived growth factor-BB; suture; tendon repair.

Figure 1.

(a) Amount of rhPDGF-BB released from the coated sutures at each time point in vitro and (b) the cumulative amount of rhPDGF-BB released from the coated sutures in vitro plotted on a semilogarithmic scale. The amounts released in vitro were normalized by the length of the suture (ng/cm). rhPDGF-BB: recombinant human platelet-derived growth factor-BB.

Figure 2.

Representative polarized light microscopy images showing collagen organization in the repaired regions of the tendons for (a) Group 1, (b) Group 2, (c) Group 3, and (d) Group 4. Bright exposure under polarized light indicates collagen that is highly aligned along the direction of loading, while areas of darker exposure (arrows) indicate regions of decreased collagen organization/alignment. (b–d) A trend for increased collagen organization (decreased observations of unorganized tissue) was observed in the rhPDGF-BB-treated groups (scale bar = 500 µm). rhPDGF-BB: recombinant human platelet-derived growth factor-BB.