Histomorphometric description of allograft bone remodeling and union in a canine segmental femoral defect model: A comparison of rhBMP‐2, cancellous bone graft, and absorbable collagen sponge

Abstract

The purpose of this study was to determine the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) on the histomorphometry of femoral allograft-host bone union and allograft remodeling. A 6 cm mid-diaphyseal femoral defect was created and filled with an allograft stabilized with an interlocking nail in 21 dogs. Dogs were randomly divided into three equal groups and the allograft-host bone junctions and the mid-diaphyses of the allografts were treated with either an absorbable collagen sponge (ACS) loaded with rhBMP-3 (BMP group), an autogenous cancellous bone graft (CBG group), or ACS loaded with buffer solution (ACS group). All dogs received daily tetracycline until sacrifice at 24 weeks to label new bone formation. Histomorphometric analyses on sections of proximal and distal allograft-host bone junctions and the mid-diaphyseal portion of allografts were performed using fluorescent and regular light microscopy. Analyses of the host bone and junctions between allograft and host bone revealed significantly greater new bone formation and larger osteon radii in the BMP group compared to CBG and ACS groups and contralateral intact bone. Porosity in CBG and ACS groups was significantly higher than in the BMP group, which had similar values to intact bone. In transverse sections of allografts, the largest pore diameters were present in the CBG group. Based on all parameters measured, significantly higher bone turnover occurred in the outer cortical area of the allograft in all groups as compared to the inner cortical and mid-cortical areas. New bone formation and osteon radiuslosteon width in allografts were similar for all three groups. Higher porosity and larger pore diameters in the CBG and ACS groups suggested higher bone resorption versus formation in these groups compared to the BMP group. The results of this study reveal more balanced allograft bone resorption and bone formation in the BMP group, with greater resorptive activity in the CBG and ACS groups. However, neither rhBMP-2 nor autogenous bone graft increased allograft incorporation when compared to the negative control (ACS group).

Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft

“…Clinically, rhBMP-2 has been used to overcome the limitations of bone grafting such as slow healing and nonunion. Scaffold-based BMP delivery, especially on an absorbable collagen sponge (eg, ACS-rhBMP-2), has become popular as a clinical therapeutic alternative, at least in the United States, on the basis of promising animal and clinical results [20,24,35,37,38,46]. However, evidence of large doses of rhBMP-2 leading to instances of heterotopic ossification, excessive inflammation, or poor bone structure has led to concerns regarding its clinical use, where an exact dose-response relationship has not been determined [6,37,38,47].…”

“…Allograft has reduced osteoinductive potential and slower healing, whereas demineralized scaffolds lack structural stability [1,13,19,25]. The widespread use of recombinant human BMP-2 (rhBMP-2) highlights its capability to augment large segmental bone defect repair, especially in the context of animal studies, with BMP-2 supplementation showing improved healing compared with allograft and ceramic fillers [25,46]. Concerns about BMP-2 side effects, optimal delivery scaffolds, and BMP-2 release kinetics notwithstanding, rhBMP-2 delivered in an absorbable collagen sponge (ACS-rhBMP-2) has become a popular clinical alternative to bone grafting in the United States while tunable delivery systems with tailored BMP release kinetics are sought [28,47].…”

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

“…Some BMPs can induce bone formation in mice, rats, rabbits, sheep, dogs, monkeys, and baboons. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] Purified BMP-2, BMP-4, and BMP-7 have been used in human clinical cases to repair resistant nonunions and segmental defects of long bones. [19][20][21][22][23] In a previous study, the ability of recombinant human BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, and BMP-7 to stimulate DNA synthesis was compared in cultures of periosteal cells and epiphyseal and sternal chondrocytes of embryonic chick.…”

Compressed homologous cancellous bone and bone morphogenetic protein (BMP)-7 or bone marrow accelerate healing of long-bone critical defects

“…osteoinductive insufficiency or structural bone loss. Numerous pre-clinical and clinical studies have provided evidence that bone morphogenetic proteins (BMPs) enable healing of critical-size long-bone defects [6,8,16,21,22,23] and are beneficial in hip reconstructive procedures [7]. The osteogenic properties of BMP-7 have been demonstrated in rabbits and dogs [6], and BMP-2 has been successfully used to treat large bone defects and to promote spinal fusion [6,12,16].…”