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.

The repair of large bone defects in clinic is a challenge and urgently needs to be solved. Tissue engineering is a promising therapeutic strategy for bone defect repair. In this study, hydrogel microspheres (HMs) were fabricated to act as carriers for bone marrow mesenchymal stem cells (BMSCs) to adhere and proliferate. The HMs were produced by a microfluidic system based on light-induced gelatin of gelatin methacrylate (GelMA). The HMs were demonstrated to be biocompatible and non-cytotoxic to stem cells. More importantly, the HMs promoted the osteogenic differentiation of stem cells. In vivo, the ability of bone regeneration was studied by way of implanting a BMSC/HM system in the cranial defect of rats for 8 weeks. The results confirmed that the BMSC/HM system can induce superior bone regeneration compared with both the HMs alone group and the untreated control group. This study provides a simple and effective research idea for bone defect repair, and the subsequent optimization study of HMs will provide a carrier material with application prospects for tissue engineering in the future.

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The purpose of this study was to develop a novel β-tricalcium phosphate (TCP)/poly (D,L-lactic-co-glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/ PLGA composite scaffold was fabricated by cryogenic three-dimensional printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope. To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/Dead Viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western blotting. The in vitro results showed that the rapamycin-loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/ PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with micro-computed tomography scanning, hematoxylin-eosin, Masson, and immune-histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin-loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering.