BMP-2 Incorporated in a Tricalcium Phosphate Bone Substitute Enhances Bone Remodeling in Sheep

Abstract

Bone morphogenetic protein-2 (BMP-2) is a well-known osteoinductive protein, which requires a carrier for local application. As an alternative to the previously described carriers, an in situ hardening, resorbable, and osteoconductive beta-tricalcium phosphate cement (TCP) is tested. Trepanation defects in the bovine distal femoral epiphysis are filled with a composite consisting of TCP and 200 microg rhBMP-2 per cm3 TCP, autologous bone graft, pure TCP, or left empty. A radiological follow-up is performed after 7 weeks and 3 months. The sheep are euthanized and bone samples are analyzed by microradiography, histology, and histomorphometry. Microradiography and histology show similar results for pure TCP and the composite. The defects are filled with trabecular bone and newly formed bone is in close contact with the remaining TCP-particles. The majority of the cement is resorbed, in the composite group the amount of remaining cement particles is reduced. Defects treated with autologous bone graft are filled completely, while untreated defects shows only a small amount of bone originating from the rim of the defect. Histomorphometry of the defects treated with pure TCP shows a significantly increased bone content in comparison to defects treated with the composite or autologous bone graft. Analysis of the remaining cement particles shows significantly less cement in the TCP/rhBMP-2 group in comparison to pure TCP. The sum of bone and cement content in the rhBMP-2 group shows amounts comparable to the calcified structures found following autologous bone grafting. The addition of rhBMP-2 to the TCP leads to faster remodeling of the defect comparable to autologous bone graft, while defects treated with pure TCP are not completely remodeled.

Current trends and future perspectives of bone substitute materials – From space holders to innovative biomaterials

“…The current functions of BSM are as follows space maintenance for bone regeneration pre-setting of the desired anatomical form supporting functions for the periosteum and associated membranes acceleration of bone remodelling osteoconductive structural guidance for the regeneration of osseous tissue carrier substance for antibiotics, growth factors or approaches by gene therapy (Rupprecht et al, 2007;Fischer et al, 2011;Maus et al, 2008a;Smeets et al, 2009b;Kolk et al, 2011) scaffolds for tissue engineering approaches (Handschel et al, 2009a;Naujoks et al, 2011) The morbidity associated with autogenous bone graft harvest and concerns regarding transmission of live viruses from allografts have been the impetus for research into a variety of bone grafting materials. Current requirements for an ideal BSM are rigorous, as listed below: biocompatibility osteoinduction and osteopromotion/osteoconduction porosity stability under stress resorbability/degradability plasticity sterility stable and long-term integration of implants Biocompatibility ensures the absence of toxicity, teratogenity or carcinogenicity.…”

Controlled Multiple Growth Factor Delivery from Bone Tissue Engineering Scaffolds via Designed Affinity

“…This is consistent with previous work with other porous implants in which fibrous and/or bone tissue inflitration has been observed. 35,50 At both 2 and 4 weeks, we observed a thin fibrous capsule around the outer surface of the scaffold as well as around the pores (Fig. 9).…”

Recommendations and Considerations for the Use of Biologics in Orthopedic Surgery

“…[59] CaP cements can also be used as delivery systems for therapeutic peptides, antibacterials, anticancer drugs, anti-inflammatory drugs, or growth factors. [60] …”