Engineered periosteum-bone biomimetic bone graft enhances posterolateral spine fusion in a rabbit model

Abstract

Background context: Bone marrow derived mesenchymal stem cells (BMSCs) and periosteum-derived cells (PDCs) have shown great viability in terms of osteogenic potential and have been considered the major cellular source for skeletal tissue engineering. Using a PDCs-impregnated cell sheet to surround a BMSCs-impregnated tricalcium phosphate (TCP) scaffold might create a periosteum-bone biomimetic bone graft substitute to enhance spine fusion.

Purpose: The purpose of this study was to determine the feasibility of using this newly tissue-engineered biomimetic bone graft for posterolateral spine fusion.

Study design/setting: This study design was based on an animal model using adult male New Zealand White rabbits.

Methods: New Zealand White rabbits underwent operation and were divided into three groups based on the experimental material implanted in the bilateral L4-L5 intertransverse space. Group 1 was BMSCs-free TCP wrapped in a PDCs-free cell sheet. Group 2 was BMSCs-loaded-TCP wrapped in a PDCs-free cell sheet. Group 3 was BMSCs-loaded-TCP wrapped in a PDCs-loaded cell sheet. After 12 weeks, six rabbits from each group were euthanized for computed tomography scanning, manual palpation, biomechanical testing, and histology. Each group had 12 radiographic fusion areas for analysis because the right and left intertransverse fusion areas were collected separately.

Results: Radiographic union of 12 fusion areas for groups 1, 2, and 3 was 0, 3, and 9, respectively. Group 3 had significantly higher fusion success than groups 1 and 2 (p<.001). Solid fusion of six fusion segments in each group by manual palpation was 0, 1, and 5, accordingly. Group 3 had a higher successful solid fusion rate than groups 1 and 2 (p=.005). The average maximal torques at failure were 727±136 N mm, 627±91 N mm, and 882±195 N mm for groups 1, 2, and 3, accordingly. The maximal torque was significantly higher in group 3 than in group 2 (p=.028). Histological evaluation verified that new bone regeneration were greater in the group 3 samples.

Conclusions: The results indicated the potential of using a PDCs-impregnated cell sheet to surround the BMSCs-impregnated TCP scaffold for creating a periosteum-bone biomimetic bone graft substitute to enhance bone regeneration and posterolateral fusion success.

Keywords: Artificial cell sheet; Bone marrow mesenchymal stem cells; Bone regeneration; Periosteum-derived cells; Posterolateral fusion; Tissue-engineered bone graft.