Abstract: OPTIMAL MURINE CRANIAL DEFECT RECONSTRUCTION UTILIZING A NOVEL COLLAGEN SCAFFOLD AND rhBMP2 WITH ANALYSIS UTILIZING CONFOCAL MICROSCOPY (Plastic Surgery 2015)

Monday, October 19, 2015: 11:10 AM

Christopher L Madsen, MD , Department of Plastic and Reconstructive Surgery, The Johns Hopkins University, Baltimore, MD

Denver M Lough, MD, PhD , Department of Plastic & Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD

Qiongyu Guo, PhD , Department of Plastic & Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD

Edward W Swanson, MD , Department of Plastic & Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD

Nikolai Sopko, MD, PhD , Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

Devin Miller, BA , Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

Gerald Brandacher, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Anand R Kumar, MD , Department of Plastic & Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD

Presentation PDF file

Introduction

Although tremendous advancements in the surgical reconstruction of large craniofacial defects have been made, a large proportion of patient outcomes remain unfavorable. Patients with combat and civilian trauma, craniectomy for various intracranial pathologies and large en-bloc tumor resections are often left with few reconstructive options. Technical challenges that exist in the reconstruction of larger and more complex craniofacial defects are pronounced due to a higher incidence of infection, soft tissue erosion, extrusion, and migration. This study aims to further delineate the role of recombinant human bone morphogenetic protein-2 (rhBMP2) by determining the smallest dose required for maximal bone regeneration when delivered in a novel collagen scaffold.

Methods

Utilizing a murine model, C57BL/6 (n=31) mice received two identical 5mm full-thickness craniectomy defects (61.6 mm²) using a standardized micro-drill core bit. The mice were divided into 7 groups consisting of: craniectomy without treatment (Group 1, n=3, negative control), craniectomy with collagen only (Group 2, n=3), craniectomy, collagen and 0.1µg rhBMP2 (Group 3, n=5), craniectomy, collagen and 1.0µg rhBMP2 (Group 4, n=5), craniectomy, collagen and 2.5µg rhBMP2 (Group 5, n=5), craniectomy, collagen and 4µg rhBMP2 (Group 6, n=5), and craniectomy, collagen and 5.0µg rhBMP2 (Group 7, n=5). Mice underwent CT imaging at 2 and 8 weeks to assess volumetric calvarial bone regeneration.

Results

The mice in Group 1 who received craniectomy without treatment and those in Group 2 who received craniectomy with collagen only, showed no appreciable healing at 8 weeks (p<0.05). Our preliminary data suggests a dose response curve for Groups 3-5, whereby statistically significant stepwise increases in bone regeneration occur as the dose of rhBMP2 increases from 0.1µg to 4µg (P<0.05); however no appreciable increase in bone regeneration occurs at rhBMP2 doses >4µg (Groups 6 and 7). The optimal dose of rhBMP2 to heal a 61.6 mm² defect in our study appears to consistently augment bone regeneration with >50% healing observed at 8 weeks (p<0.05).

Conclusions

Current surgical reconstruction of large craniofacial defects remains challenging and associated with a high incidence of complications. The determination of an optimal dose of rhBMP2 delivered in a novel collagen scaffold, as outlined here in a murine cranial defect, facilitates further evaluation of rhBMP2 when used alone or in combination with other biologic products to reconstruct large craniofacial defects.

28065 OPTIMAL MURINE CRANIAL DEFECT RECONSTRUCTION UTILIZING A NOVEL COLLAGEN SCAFFOLD AND rhBMP2 WITH ANALYSIS UTILIZING CONFOCAL MICROSCOPY