Coating with a modular bone morphogenetic peptide promotes healing of a bone-implant gap in an ovine model

Abstract

Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed "modular bone morphogenetic peptide (mBMP)", which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle. The mBMP molecules efficiently bound to a hydroxyapatite-titanium implant and 64% of the initially bound mBMP molecules were released in a sustained manner over 28 days. The results demonstrated that the mBMP-coated implant group had significantly more mineralized bone filling in the implant-bone gap than the control group in C-arm computed tomography (DynaCT) scanning (25% more), histological (35% more) and microradiographic images (50% more). Push-out stiffness of the mBMP group was nearly 40% greater than that of control group whereas peak force did not show a significant difference. The results of this study demonstrated that mBMP coated on a hydroxyapatite-titanium implant stimulates new bone formation and may be useful to improve implant fixation in total joint arthroplasty applications.

Figure 1. Image of mBMP coated HAP-titanium implant and surgical implantation in sheep medial femoral condyle.

Figure 2. Images of release profile of mBMP in vitro.

(A) Cumulative release of mBMP from HAP-titanium implant in SBF is over 60% at 4 weeks. (B) Fluorescent images of an implant after incorporation with fluorescently labeled mBMP (top) and after 4-week incubation in simulated body fluid (SBF) (bottom).

Figure 3. Images of Dyna CT results between control and mBMP coated implants.

A: Control, DynaCT demonstrating that gap between the implant and host bone was still visible (white arrows). B: The gap between mBMP coated HAP-implant and host bone was filled with high density mineralized tissue.

Figure 4. Microradiographic calculation of new bone formation in the gap demonstrating mBMP group had significantly more new bone ingrowth than non-mBMP group at 3 levels of the implant and in total amount.

“*” means significant difference between treatments (p<0.05).

Figure 5. High detailed radiograph (A, B) and histologic section (C, D) of non-mBMP coated HAP-implants (A, C) and mBMP-coated implants (B, D).

In C and D, areas between white arrows highlighted original 1-mm gap between the implant and host bone.

Figure 6. Histologic calculation of new bone formation in the implant-bone gap on the Goldner’s trichrome staining slides demonstrated that middle section and total 3 sections of mBMP coated implant had significantly more new bone formation compared to control.

“*” means significant difference between treatments (p<0.05).