Paclitaxel-loaded Bone Acellular Extracellular Matrix Injectable Hydrogel for Osteosarcoma Treatment.

A novel local chemotherapy delivery system was developed to improve the therapeutic efficacy of paclitaxel (PTX) for osteosarcoma while reducing systemic toxicity, low bioavailability, and tumor recurrence. PTX-loaded polylactic-co-glycolic acid nanoparticles (PLGA/PTX) were fabricated by an emulsification solvent evaporation method. Meanwhile, low-immunogenicity bone extracellular matrix (ECM) was prepared from porcine/bovine femurs through gradient decellularization combined with physical, chemical, and enzymatic treatments, followed by pepsin digestion to create a temperature-responsive injectable hydrogel. PLGA/PTX nanoparticles were incorporated into the bone ECM pre-gel to form a composite hydrogel system (H@PLGA/PTX). The processed bone ECM achieved over 97% decellularization while preserving collagen structure and biocompatibility. The composite hydrogel exhibited a porous three-dimensional network and released 62.5 ± 4.5% of PTX within 48 hours under mildly acidic conditions (pH 6.5). In vitro assays showed superior anti-tumor effects against MG-63 osteosarcoma cells compared with free PTX. In vivo studies demonstrated significant tumor inhibition, stable body weight, and prolonged survival, associated with enhanced Caspase-3-mediated apoptosis. Overall, H@PLGA/PTX provides sustained local drug release with strong anti-tumor activity and low systemic toxicity, offering a promising strategy for adjuvant osteosarcoma chemotherapy.