Tang, Tianyi; (2025) Degradable Phosphate Glass Microspheres Seeded into 3D Printed Scaffold for Applications in Osteochondral Tissue Engineering. Doctoral thesis (Ph.D), UCL (University College London).

Text Tianyi Tang - PhD Thesis - Final version.pdf - Accepted Version Access restricted to UCL open access staff until 1 November 2026. Download (23MB)

Abstract

INTRODUCTION: Osteochondral tissue engineering remains challenging as it involves the simultaneous regeneration of cartilage and subchondral bone. Phosphate bioactive glass microspheres, known for their degradability and biocompatibility, offer a promising platform to address this challenge through delivery, expansion, and differentiation of target cells. This study aimed to develop a series of ZnO-TiO2-CaO-Na2O-P2O5 glass microspheres as microcarriers and explore their integration within a multi-layered 3D-printed scaffold for osteochondral regeneration. MATERIALS AND METHODS: ZnO-TiO2-CaO-Na2O-P2O5 glass microspheres containing 0-10 mol% ZnO were synthesised and characterised by X-ray diffraction, Fourier-transform infrared-spectroscopy, differential thermal analysis, and scanning electron microscopy. In vitro biocompatibility and differentiation were evaluated using MC3T3-E1 pre-osteoblasts, ATDC5 chondrogenic cells, and human adipose-derived stem cells (ADSCs). 3D-printed scaffolds with gradient pore sizes were fabricated using CSMA-2 polymer, selectively incorporating microspheres of defined size ranges to reconstruct specific osteochondral layers. RESULTS: ZnO-TiO2-CaO-Na2O-P2O5 glass microspheres with ≤5 mol% ZnO supported cell adhesion and proliferation across MC3T3-E1 cells, ATDC5 cells, and ADSCs. Microspheres with 3-5 mol% ZnO significantly promoted osteogenic differentiation in MC3T3-E1 cells, enhancing mineralisation and BMP2 expression. Microspheres with ≤3 mol% ZnO facilitated extracellular matrix deposition and osteogenic differentiation of ATDC5 cells and ADSCs, respectively. Strategic incorporation of microspheres within the 3D-printed CSMA-2 scaffold allowed size-selective spatial microsphere distribution. DISCUSSION AND CONCLUSIONS: ZnO-TiO2-CaO-Na2O-P2O5 glass microspheres function as versatile microcarriers, supporting multiple cell types and enhancing proliferation and extracellular matrix deposition. Additional ZnO doping primarily improves osteogenic differentiation, while further compositional optimisation may enhance regenerative potential. Selective integration of microspheres within 3D-printed scaffolds facilitates precise microcarrier distribution and may help guide cells toward bone or cartilage-specific regions, enabling spatially controlled formation of osteochondral tissues. Present results from in vitro studies highlight the significant potential of phosphate glass microspheres for advancing osteochondral regeneration strategies, and more comprehensive research is required to further validate their efficacy.

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