A modified rabbit ulna defect model for evaluating periosteal substitutes in bone engineering: a pilot study.

Rania M El Backly,Federico Santolini,Ranieri Cancedda,Giuliana Tromba,Anita Muraglia,Maddalena Mastrogiacomo,Danilo Chiapale,Chiara Ottonello

doi:10.3389/fbioe.2014.00080

Abstract

The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX®) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX®) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute.

Highlights

Metaphyseal long bone defects in animal models are commonly used to evaluate bone repair/regeneration since a high proportion of fracture injuries in human beings occur in long bones
Several studies have used this model to evaluate the efficacy of tissue-engineered constructs to enhance bone repair, including the use of allogenic peripheral blood-derived mesenchymal stem cells associated with ceramic scaffolds (Wan et al, 2006), adipose-derived stromal vascular fraction (SVF) cells (Kim et al, 2012), novel alloy-based scaffolds (Smith et al, 2012), tri-phasic release of rhBMP-2 (Bae et al, 2011), and platelet-rich plasma (Kasten et al, 2008)
RADIOGRAPHIC ASSESSMENT AND COMPUTED MICROTOMOGRAPHY ANALYSIS Post-operative radiographs for group (Ia) showed a thickening of the radial cortical plate facing the defect area with formation of radio-ulnar fusion while the defect area itself remained devoid of new bone formation (Figure 3A)

Summary

Introduction

Metaphyseal long bone defects in animal models are commonly used to evaluate bone repair/regeneration since a high proportion of fracture injuries in human beings occur in long bones. Several studies have used this model to evaluate the efficacy of tissue-engineered constructs to enhance bone repair, including the use of allogenic peripheral blood-derived mesenchymal stem cells associated with ceramic scaffolds (Wan et al, 2006), adipose-derived stromal vascular fraction (SVF) cells (Kim et al, 2012), novel alloy-based scaffolds (Smith et al, 2012), tri-phasic release of rhBMP-2 (Bae et al, 2011), and platelet-rich plasma (Kasten et al, 2008) All of these studies showed a clear fusion between the radius and the ulna at the sites of defect formation as a biologic response from cells from the surrounding tissues, masking the contribution of the implanted construct (Kasten et al, 2008). Periosteal remnants from the proximal and distal ends of the defect, in addition to the membrana interossea found between the two bones, may well be responsible for the synostosis or fusion between the radius and the ulna of the rabbit in these bone regeneration studies (Bodde et al, 2008)

Methods

Results

Discussion

Conclusion