Thermo-engineered zinc-alginate and pectin stabilized hydroxyapatite microspheres: A synergistic approach for bone repair and drug delivery

Abstract

This study reports the development of thermally engineered Zn-alginate-pectin stabilized hydroxyapatite (pHAP) microsphere for enhanced bone repair and targeted drug delivery. The microspheres were synthesized via a green route using carrot pomace-derived pectin mediated HAP with alginate, offering a biocompatible and biodegradable platform that mimics bone mineral. Incorporation of Zn²⁺ through Zn(NO₃)₂ cross-linking improved osteo conductivity, while calcination at 1000 °C facilitated phase transformation and zinc substitution into the HAP lattice, enhancing structural integrity and bioactivity. In vitro studies using MG-63 cells confirmed improved cell proliferation, ALP activity, and biomineralization, supporting their role in bone repair. In parallel, the system served as an efficient drug delivery platform by separately loading doxorubicin (DOX) and methotrexate (MTX). Drug release studies for both the drugs revealed a sustained and pH-responsive profile, with faster release under acidic conditions mimicking the tumour microenvironment. Cytotoxicity assays on MCF-7 and A549 cancer cells demonstrated significant, dose-dependent antiproliferative effects, with DOX-loaded microspheres showing higher potency. Apoptotic analysis (AO/EB and Hoechst staining) and migration/invasion studies (Scratch and Trans well assays) confirmed enhanced cancer cell inhibition. This dual-functional microsphere combines structural support for bone regeneration with controlled, localized chemotherapeutic delivery. The outcome results of this study highlighted that the integration of thermal engineering with biopolymers and zinc doping presents a unique and effective strategy.