A bifunctional bortezomib-loaded porous nano-hydroxyapatite/alginate scaffold for simultaneous tumor inhibition and bone regeneration

Abstract

Treatments of osteolytic lesions due to malignant metastasis remain one of the major clinical challenges. The residual tumor cells after surgical resections and an acidic tumor microenvironment are unfavorable for osteogenic induction. Bortezomib (BTZ), a proteasome inhibitor used in chemotherapy, also has an osteogenic potential in concentration- and Ca2+-dependent manners. In this study, controlled delivery of BTZ in a novel bifunctional scaffold based on nano-hydroxyapatite (nHA) and sodium alginate (SA) nanocomposite, namely BTZ/nHA@SA, has been explored. By smartly adjusting microenvironments, a sustainable release of Ca2+ from nHA could be achieved, which was not only able to cross-link SA but also to regulate the switch between the dual functions of tumor inhibition and bone regeneration of BTZ to promote the osteogenic pathway. The freeze-dried BTZ/nHA@SA scaffold has excellent interconnectivity, is capable to promote the attachment and proliferation of mouse embryonic osteoblast precursor cells, as well as effectively induces breast cancer cell death in vitro. Furthermore, in vivo, studies using a mouse tumor model and a rabbit femoral defect model showed that the BTZ/nHA@SA scaffold could promote tumor ablation, and also enhance bone repair. Therefore, the BTZ/nHA@SA scaffold has unique dual functions of inhibiting tumor recurrence and promoting bone tissue regeneration simultaneously. This smart bi-functional scaffold offers a promising novel approach for oncological treatments by synchronously orchestrating tumor inhibition and tissue regeneration for the repair of neoplastic bone defects.

Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration

“…Most biomimetic mineralization approaches are conducted in aqueous environments with controllable conditions. As a calcium phosphate crystal derivative, hydroxyapatite (HA) is the main inorganic substance existing in natural bone tissue and possesses unique crystallographic nanostructures, hierarchically arranged between the collagen fibrils [ 12 ]. In vitro, due to similar components to native bone tissue, HA has been widely used as a calcium–phosphate (CaP)-based bone substitute for bone regeneration.…”

Biodegradable Nanoflowers with Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration

“…Interestingly, this flower-like structure could release bioactive ions including Ca 2+ and PO 4 3− for the joint bone remodeling process. 33,34 The Ca 2+ released from flower also could create the in situ biomineralization layer, thus providing an "osteogenic microenvironment" for the BMSCs' osteogenic induction. 35 The interface integration by appropriate calcium chelation Ca 2+ was efficient for the osteogenesis; 36 herein, the bioactive flower-like structure served as ion carrier and pool which could release Ca 2+ /PO 4 3− for the micro-calcium phosphate formation.…”