Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration

Abstract

Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dyepolyethylene glycol@sodium alginate hydrogel and poly(Llactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable ostealmicroenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

Productizing Nano-Bioactive Glass-Based Bilayer Scaffolds: A Graft for Reconstruction of Mandibular and Femoral Bone Defects

“…Our design strategy focuses on a two-layered structure, catering to the distinct requirements of both soft and hard tissues within the mandibular bone defect for optimal repair effects. Bilayers contain two layers with different structures and functions; it can be designed to mimic normal skin tissue by providing a protective barrier with a hydrophobic outer layer and a hydrophilic inner layer. , The outer layer of the bilayer scaffold can provide other benefits, such as increasing scaffold strength, providing a hydrophobic and antibacterial surface, and accelerating the wound healing process . In other words, alginate/gelatin can maintain the environment of the defect site and prevent bacterial invasion through its superstructure by delivering drugs.…”