Repair of long bone defects of large size using a tissue-engineered periosteum in a rabbit model

Lin Zhao,Guangtie Ren,Junli Zhao,Zhenhe Tuo

doi:10.1007/s10856-021-06579-7

Abstract

Tissue engineering is a promising approach for bone regeneration. In this study, we aimed to investigate whether tissue engineered periosteum (TEP), which was fabricated by combining osteogenically-induced mesenchymal stem cells (MSCs) with porcine small intestinal submucosa (SIS), could restore long bone defects of large size in rabbits. Twenty-four adult New Zealand white rabbits (NZWRs) were used in the experiments. Long bone defects of large size (30 mm-50 mm; average, 40 mm) were established on both sides of NZWRs’ radii. The defects were treated with TEP (Group A), allogeneic deproteinized bone (DPB, Group B), TEP combined with DPB (Group C), and pure SIS (Group D). The healing outcome was evaluated by radiography and histological examination at 4, 8, and 12 weeks post-treatment. The radiographical findings showed that bone defects of large size were all repaired in Groups A, B and C within 12 weeks, whereas Group D (pure SIS group) failed to result in defect healing at 4, 8, and 12 weeks. Although there was some new bone regeneration connecting the allografts and bone ends, as observed under radiographical and histological observations, bone defects of large sizes were restored primarily by structurally allografted DPB within 12 weeks. The TEP groups (Groups A and C) showed partial or total bone regeneration upon histological inspection. Based on 12-week histological examinations, significantly more bone was formed in Group A than Group C (P < 0.05), and both groups formed significantly more bone than in Groups B and D. The results indicated that long bone defects of a large size could be restored by TEP or TEP combined with the DPB scaffold, and such materials provide an alternative approach to resolving pathological bone defects in clinical settings.

Highlights

Segmental bone defects due to trauma, cancer, or congenital deformity are major clinical challenges [1, 2]
Large-bone regeneration has failed previously due to the lack of the vascularization within the bone tissue engineering (BTE) constructs and slow penetration of the host vasculature; resulting in poor implant survival and integration [6, 7]
The osteogenic differentiation was further identified by AKP staining (Fig. 2c), and the formation of mineralized nodules determined by Alizarin Red staining (Fig. 2d)

Summary

Introduction

Segmental bone defects due to trauma, cancer, or congenital deformity are major clinical challenges [1, 2]. While much effort has been devoted to BTE, very little of such research has been translated to the clinic [1, 4]. Large-bone regeneration has failed previously due to the lack of the vascularization within the BTE constructs and slow penetration of the host vasculature; resulting in poor implant survival and integration [6, 7]. In the absence of capillary networks within the 3D implants, the engineered tissues can only have a maximum thickness of 150–200 mm; dimensions larger than this threshold may result in a lack of oxygen inside the biomaterials [8]

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Conclusion