The integration of structure and function for tissue engineering scaffolds is of great importance in mimicking native bone tissue. However, the complexity of hierarchical structures, the requirement for mechanical properties, and the diversity of bone resident cells are the major challenges in constructing biomimetic bone tissue engineering scaffolds. Herein, a Haversian bone–mimicking scaffold with integrated hierarchical Haversian bone structure was successfully prepared via digital laser processing (DLP)–based 3D printing. The compressive strength and porosity of scaffolds could be well controlled by altering the parameters of the Haversian bone–mimicking structure. The Haversian bone–mimicking scaffolds showed great potential for multicellular delivery by inducing osteogenic, angiogenic, and neurogenic differentiation in vitro and accelerated the ingrowth of blood vessels and new bone formation in vivo. The work offers a new strategy for designing structured and functionalized biomaterials through mimicking native complex bone tissue for tissue regeneration.

Osteoarthritis not only results in cartilage lesion, but also is accompanied with subchondral bone damage caused by the inflammatory response. It is of great significance to treat osteoarthritis by regulating the immune response. As copper (Cu) plays an essential role in immune response and anti-arthritis, a copper-incorporated bioactive glass-ceramics (Cu-BGC) may achieve the aim of healing cartilage lesion and reducing inflammatory response caused by osteoarthritis. We hypothesized that the Cu2+ released from Cu-BGC scaffolds may satisfy the requirements of cartilage regeneration and anti-arthritis.Methods: 3D-printing method was employed to prepare Cu-BGC scaffolds. The stimulating effect on the chondrocytes and macrophages cultured with Cu-BGC extracts was investigated. Furthermore, the in vivo regenerative effect of Cu-BGC scaffolds on osteochondral defects was studied.Results: The incorporation of Cu2+ into BGC considerably promoted the proliferation and maturation of chondrocytes, and induced macrophages shifting to anti-inflammatory phenotype. Histological analysis demonstrated that the Cu-BGC scaffolds meaningfully improved the regeneration of cartilage and elevated the recovery of the osteochondral interface as compared with the CTR and BGC groups. The potential mechanism is related to Cu2+ ions triggering the immune response of cartilage via activating HIF signaling pathway and inhibiting the inflammatory response in osteochondral tissue.Conclusion: These results demonstrated that Cu-BGC scaffolds significantly facilitated the regeneration of cartilage and osteochondral interface, as well as inhibited inflammatory response, which may prevent the development of osteoarthritis associated with osteochondral defects.

Treatment of osteochondral defects remains a great challenge in clinical practice because cartilage and subchondral bone possess significantly different physiological properties. In this study, the controlled surface micro/nanometer structure of bioactive scaffolds in a combination of biomaterial chemistry is harnessed to address this issue. Model bioactive biomaterials, bredigite (BRT) scaffolds, with controlled surface micro/nanostructure are successfully fabricated by combining 3D printing with a hydrothermal process. It is found that the growth of micro/nano–calcium phosphate crystals on the surface of BRT scaffolds notably enhances their compressive strength by healing the microcracks on the strut surface. The micro/nanostructured surface distinctly facilitates the spread and differentiation of chondrocytes by activating integrin αvb1 and α5b1 heterodimers, regulates cell morphology, and promotes osteogenic differentiation of rabbit bone marrow stromal cells (rBMSCs) through the synergetic effect of integrin α5b1 and RhoA, in which the microrod surface demonstrates the highest stimulatory effect on the differentiation of chondrocytes and rBMSCs. The in vivo study shows that the micro/nanostructured surface of the 3D printed scaffolds obviously promotes the regeneration of both cartilage and subchondral bone tissues. This study suggests that the construction of controlled micro/nanostructured surface in porous 3D scaffolds offers a smart strategy to induce bilineage bioactivities for osteochondral regeneration.

For the postoperative treatment of bone cancer, biomaterials should possess an antitumor effect and simultaneous repair ability of bone defects. Compared with single photothermal treatment or magnetothermal treatment, photo/magnetothermal joint treatment represents a more high-efficient strategy to kill tumor cells. In this work, a 3D-printed bioceramic scaffold with a photo/magnetothermal effect was successfully designed and fabricated, which exhibited the function of killing tumor cells and excellent osteogenic bioactivity, via incorporating an Fe element into akermanite (AKT) bioceramics. After doping with ferric elements, the AKT scaffolds possessed significantly enhanced compressive strength and desirable ferromagnetic property. The ferric elements endowed the AKT scaffolds with excellent photo/magnetothermal effects, and hence the scaffolds could efficiently kill tumor cells in vitro under mild laser power density and magnetic field. In addition, the Fe-doped AKT bioceramic scaffolds significantly promoted cell proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells as compared with the original AKT scaffolds without Fe elements. The results suggest that Fe-doped bioceramic scaffolds with both photo/magnetothermal effect and in vitro osteogenic bioactivity could be a promising biomaterial for the synergistic therapy of bone cancers.