Abstract
The repair of large bone defects with complex geometries remains a major clinical challenge. Here, we explored the feasibility of fabricating polylactic acid-hydroxyapatite (PLA-HA) composite scaffolds. These scaffolds were constructed from vascularized tissue engineered bone using an in vivo bioreactor (IVB) strategy with three-dimensional printing technology. Specifically, a rabbit model was established to prefabricate vascularized tissue engineered bone in two groups. An experimental group (EG) was designed using a tibial periosteum capsule filled with 3D printed (3DP) PLA-HA composite scaffolds seeded with bone marrow stromal cells (BMSCs) and crossed with a vascular bundle. 3DP PLA-HA scaffolds were also combined with autologous BMSCs and transplanted to tibial periosteum without blood vessel as a control group (CG). After four and eight weeks, neovascularisation and bone tissues were analysed by studying related genes, micro-computed tomography (Micro-CT) and histological examinations between groups. The results showed that our method capably generated vascularized tissue engineered bone in vivo. Furthermore, we observed significant differences in neovascular and new viable bone formation in the two groups. In this study, we demonstrated the feasibility of generating large vascularized bone tissues in vivo with 3DP PLA-HA composite scaffolds.
Highlights
The reconstruction of large size bone defects caused by tumour resection, trauma or congenital malformation remains a major clinical challenge in reconstructive, orthopaedic and craniofacial surgeries[1]
To better characterize the expression of angiogenesis and osteogenic biomarkers generated within the in vivo bioreactors, Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed for Vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) expressed during vascularisation and for OPN and COL-1, indicative of viable bone formation
The experimental group (EG) revealed significantly greater expression of all four genes compared with the control group (CG)
Summary
The reconstruction of large size bone defects caused by tumour resection, trauma or congenital malformation remains a major clinical challenge in reconstructive, orthopaedic and craniofacial surgeries[1]. To generate large bone tissues with customized geometries for repair applications and aesthetic needs to preserve natural contours, numerous approaches have been explored for bone defect reconstruction[2,3]. Tremendous advances for the construction of tissue-engineered bone have been observed, BTE has not considered the functional factors of a true regenerative microenvironment[8]. In vivo bioreactors (IVBs), which are designed to mimic in vivo microenvironments, have been explored for the repair of large bone defects for clinical applications by using an in vivo BTE approach[9]. Many studies, including our previous study, have prefabricated large vascularized tissue engineered bones and have shown the feasibility of this in vivo bioreactor approach[11,12,13]
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