Cryogenic 3D printing of porous scaffolds for in situ delivery of 2D black phosphorus nanosheets, doxorubicin hydrochloride and osteogenic peptide for treating tumor resection-induced bone defects

Abstract

Tumor resection is widely used to prevent tumor growth. However, the defected tissue at the original tumor site also causes tissue or organ dysfunction which lowers the patient’s life quality. Therefore, regenerating the tissue and preventing tumor recurrence are highly important. Herein, according to the concept of ‘first kill and then regenerate’, a versatile scaffold-based tissue engineering strategy based on cryogenic 3D printing of water-in-oil polyester emulsion inks, containing multiple functional agents, was developed, in order to realize the elimination of tumor cells with recurrence suppression and improved tissue regeneration sequentially. To illustrate our strategy, water/poly(lactic-co-glycolic acid)/dichloromethane emulsions containing β-tricalcium phosphate (β-TCP), 2D black phosphorus (BP) nanosheets, low-dose doxorubicin hydrochloride (DOX) and high-dose osteogenic peptide were cryogenically 3D printed into hierarchically porous and mechanically strong nanocomposite scaffolds, with multiple functions to treat bone tumor, resection-induced tissue defects. Prompt tumor ablation and long-term suppression of tumor recurrence could be achieved due to the synergistic effects of photothermotherapy and chemotherapy, and improved bone regeneration was obtained eventually due to the presence of bony environment and sustained peptide release. Notably, BP nanosheets in scaffolds significantly reduced the long-term toxicity phenomenon of released DOX during in vivo bone regeneration. Our study also provides insights for the design of multi-functional tissue engineering scaffolds for treating other tumor resection-induced tissue defects.

Cryogenic 3D printing of dual-delivery scaffolds for improved bone regeneration with enhanced vascularization

“…However, OP/TCP/PLGA scaffolds had a rough strut surface on which a number of micropores and numerous TCP particles (200 nm) can be observed ( Fig. 2 b and c) [ 24 ]. In comparison, after the coating of AP/collagen I hydrogel, most micropores were filled with hydrogels, and thus a relatively smooth strut surface can be observed ( Fig.…”

Black phosphorus-based 2D materials for bone therapy

“…Due to the huge surface area of GO and the phosphate released by BP's continuous oxidation, the synergistic effect of GO and BP on cell proliferation and osteogenic differentiation was played. According to the concept of "kill first, then repair and regenerate ", based on 3D printing technology at low temperature, Wang et al printed out a 3D porous nanocomposite scaffold with high mechanical strength, containing poly(lactic-co-glycolic acid) (PLGA), β-TCP, BP, DOX and BMP 2 and used this scaffold to reconstruct the defect after bone tumor resection [ 174 ] ( Fig. 10 ).…”

“…Reprinted with permissons from Ref. [ 174 ], Copyright 2020, IOP Publisher. Abbreviations: PVA, polyvinyl alcohol; TP, TCP/PLGA scaffold; PTP, P24/TCP/PLGA scaffold; DPTP, DOX/P24/TCP/PLGA scaffold; BPTP, BP/P24/TCP/PLGA scaffold; BDPTP, DOX/P24/BP/TCP/PLGA scaffold.…”

Recent Advances in Biomaterial Scaffolds for Integrative Tumor Therapy and Bone Regeneration

“…[39] Besides, Reproduced with permission. [40] Copyright 2020, Institute of Physics. the scaffolds were biocompatible and bioactive with excellent osteoconductivity, thus endowing the scaffolds with rapid new bone growth in vivo.…”

“…Wang et al functionalized -TCP scaffolds with BP nanosheets, DOX, and hydrophilic osteogenic peptide to treat bone tumor resection-induced defects. [40] Here, BP nanosheets, DOX, and peptide (P24) acted as photothermal agent, chemotherapeutic drug, and osteogenic factor, respectively ( Figure 9A). They were mixed with -TCP nanoparticles and PLGA to 3D print the DOX/P24/BP/TCP/PLGA (BDPTP) scaffolds.…”