Unified Therapeutic-Prophylactic Tissue Engineering Scaffold Demonstrated to Prevent Tumor Recurrence and Overcoming Infection toward Bone Remodeling.

Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and the large bone defects are difficulty for the patients to self-repair. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS 2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS 2 improve the hydrogel system with excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradual released Gd 3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, our strategy supplies a method to prepare multifunctional bone defect repair materials and is expected to play a significant guidance and reference to the development of biomaterials for bone tissue engineering. Osteosarcoma, a kind of malignant bone tumors, is considered to be an extremely challenging disease in clinic due to the high probability of recurrence and metastasis, leading to the 5-year overall survival rate of less than 20%. [ 1 ] Resection surgery is the traditional and most useful strategy to cure osteosarcoma, however, tumor recurrence and postoperative infection is one of the problems faced by patients after surgery. Although radiotherapy and chemotherapy have been used in clinic, systemic side effects are still inevitable. [ 2 ] Faced with such a situation, photothermal therapy (PTT), a non-invasive treatment, is of great interest to researchers and has been applied in wound healing, [ 3 ] cancer therapy, [ 4 ] metabolism adjustment, [ 5 ] and so on. Based on the reliable tissue penetration, high energy, and almost no thermal damage to the skin, 808 nm near-infrared (NIR) light has been widely applied in the medical field as a trigger for the photothermal effect. [ 7 ] Meanwhile, a series of photothermal materials have been discovered, such as black phosphorus (BP), [ 7 ] MXene, [ 8 ] black titanium dioxide, [ 9 ] etc. Molybdenum sulfide (MoS 2 ), a well-known 2D transition metal dichalcogenides (TMDCs) that is easily prepared by a hydrothermal method and has good photothermal conversion efficiency, [ 10 ] will be used in our system as the photothermal agent to prevent osteosarcoma recurrence and even bacterial infection after artificial material implantation. Compared with the mechanical exfoliation and chemical vapor deposition methods for the preparation of monolayer MoS 2 nanosheets, solution-based methods show some advantages such as high yields and relatively mild reaction conditions. It can be subdivided into liquid phase exfoliation (top-down method) and wet chemical synthesis (bottom-up method). The liquid phase exfoliation method is limited by the addition of multiple chemicals such as reaction reagents, solvents or surfactants, and its yield and quality become difficulty to control. In contrast, the wet chemical method is a typical bottom-up process to prepare MoS 2 nanosheets. This strategy has the following advantages: a) the precursors are inexpensive metal salts; b) the prepared MoS 2 nanosheets are uniform in size and high in yield; c) they can be easily dispersed and separated; and d) the diverse chemical properties and solubility provide a rich platform for chemical functionalization in solution and hybridization with other materials. [ 11 ] Thus, MoS 2 prepared by the wet chemical synthesis method show some prospects as photothermal materials. In addition, it has been confirmed that mild heat stimulation (40-45°C) can promote cell viability, leading to a self-healing or regeneration of skin, blood vessels and bone; moderate heat stimulation (45-50°C) can kill tumor and bacteria effectively by inducing the collapse of cytomembranes and inactivation of protein without influencing normal cells; while excessive thermal exposure (>55°C) would cause tissue burns and should be avoided. [ 12 ] Therefore, the influence of power density and photothermal agent concentration will also be discussed in our system. This article is protected by copyright. All rights reserved.