Effects of BMP-12-Releasing Sutures on Achilles Tendon Healing

Abstract

Tendon healing is a complex coordinated event orchestrated by numerous biologically active proteins. Unfortunately, tendons have limited regenerative potential and as a result, repair may be protracted months to years. Current treatment strategies do not offer localized delivery of biologically active proteins, which may result in reduced therapeutic efficacy. Surgical sutures coated with nanostructured minerals may provide a potentially universal tool to efficiently incorporate and deliver biologically active proteins directly to the wound. Additionally, previous reports indicated that treatment with bone morphogenetic protein-12 (BMP-12) improved tendon healing. Based on this information, we hypothesized that mineral-coated surgical sutures may be an effective platform for localized BMP-12 delivery to an injured tendon. The objective of this study was, therefore, to elucidate the healing effects of mineral-coated sutures releasing BMP-12 using a rat Achilles healing model. The effects of BMP-12-releasing sutures were also compared with standard BMP-12 delivery methods, including delivery of BMP-12 through collagen sponge or direct injection. Rat Achilles tendons were unilaterally transected and repaired using BMP-12-releasing suture (0, 0.15, 1.5, or 3.0 mg), collagen sponge (0 or 1.5 mg BMP-12), or direct injection (0 or 1.5 mg). By 14 days postinjury, repair with BMP-12-releasing sutures reduced the appearance of adhesions to the tendon and decreased total cell numbers. BMP-12 released from sutures and collagen sponge also tended to improve collagen organization when compared with BMP-12 delivered through injection. Based on these results, the release of a protein from sutures was able to elicit a biological response. Furthermore, BMP-12-releasing sutures modulated tendon healing, and the delivery method dictated the response of the healing tissue to BMP-12.

Coated Sutures

“…To test these sutures for mineral coating abilities, these sutures were coated with calcium phosphate then incubated in modified simulated body fluids to mimic an in vivo environment. 22 All sutures showed an effective mineral coating. Because of surgical requirements, the Vicryl suture was used for the in vivo experiments in rat Achilles tendon repairs.…”

“…7,16,[18][19][20][21][22] The aim of these studies was to locally deliver different growth factors such as basic fibroblast growth factor (bFGF), 20 vascular endothelial growth factor (VEGF), 8 recombinant human platelet-derived growth factor-BB (rhPDGF-BB), 21 bone morphogenetic protein (BMP)-12, or recombinant human growth and differentiation factor-5 (rhGDF-5). 16 Furthermore, sutures coated with mesenchymal stem cells (MSC) 23 or pluripotential embryonic cells 24 were developed in an attempt to integrate cells with a high capacity for proliferation and differentiation into the surgical site to promote healing.…”

“…Four hours before repair, the precoated Vicryl sutures were incubated in BMP-12 to begin absorption of the calcium phosphate surface in accordance with previously reported protein-release studies. 10,19,22,29 The authors compared the effects of the coated sutures (0, 0.15, 1.5, or 3.0 mg) to standard delivery methods such as a BMP-12-loaded collagen sponge (0 or 1.5 mg) or direct injection (0 or 1.5 mg). The authors transected rat Achilles tendons and performed the repairs with one of the previously mentioned biological augmentations.…”

“…BMP-12 released from sutures and collagen sponges also tended to improve collagen organization when compared with BMP-12 delivered via injection. 22 …”

TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model

“…TOB1 has been implicated in diverse biological activities such as dorsal development of embryos and T cell activation [13][14][15]. It is well known that bone morphogenetic protein (BMP)/Sma and mad related family (Smad) signaling can effectively improve osteoblast differentiation and tendon-bone healing [16][17][18]. TOB1 is a negative regulator of BMP/Smad signaling and negatively regulates osteoblast proliferation and differentiation by suppressing the activity of receptor-regulated Smad proteins [19].…”