Abstract

The objective of this work was to fabricate a rigid, resorbable and osteoconductive scaffold by mimicking the hierarchical structure of the cortical bone. Aligned peptide-functionalize nanofiber microsheets were generated with calcium phosphate (CaP) content similar to that of the natural cortical bone. Next, the CaP-rich fibrous microsheets were wrapped around a microneedle to form a laminated microtube mimicking the structure of an osteon. Then, a set of the osteon-mimetic microtubes were assembled around a solid rod and the assembly was annealed to fuse the microtubes and form a shell. Next, an array of circular microholes were drilled on the outer surface of the shell to generate a cortical bone-like scaffold with an interconnected network of Haversian- and Volkmann-like microcanals. The CaP content, porosity and density of the bone-mimetic microsheets were 240 wt%, 8% and 1.9 g/ml, respectively, which were close to that of natural cortical bone. The interconnected network of microcanals in the fused microtubes increased permeability of a model protein in the scaffold. The cortical scaffold induced osteogenesis and vasculogenesis in the absence of bone morphogenetic proteins upon seeding with human mesenchymal stem cells and endothelial colony-forming cells. The localized and timed-release of morphogenetic factors significantly increased the extent of osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells in the cortical scaffold. The cortical bone-mimetic nature of the cellular construct provided balanced rigidity, resorption rate, osteoconductivity and nutrient diffusivity to support vascularization and osteogenesis.

Highlights

  • There is a clinical need for tissue-engineered cellular constructs for reconstruction of large skeletal defects [1]

  • The addition of citric acid to the modified simulated body fluid (SBF) significantly increased calcium phosphate (CaP) content of the microsheets from 148 6 20 wt% based on the fiber weight to 239 6 30 wt% after 24-h incubation

  • We previously showed that hMSCþECFC/vascular endothelial growth factor (VEGF)-NG seeded microchannels within a matrix seeded with human mesenchymal stem cells (hMSCs)/bone morphogenetic protein-2 (BMP2)-NGs increased osteogenic and vasculogenic differentiation of the seeded cells [28]

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Summary

Introduction

There is a clinical need for tissue-engineered cellular constructs for reconstruction of large skeletal defects [1]. Patients with large traumatic skeletal injuries undergo multiple costly operations followed by rehabilitation mainly due to insufficient mechanical stability, lack of vascularity and inadequate resorption of the graft [3]. There is insufficient source of autograft bone for patients with large skeletal defects [5]. The use of frozen or freeze-dried allogeneic bone increases the risk of transmission of unknown pathogens [6, 7]. To this end, the overall goal of this research was to engineer a bone-mimetic scaffold as a substitute for autograft in reconstruction of large bone defects

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