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It is of significance to construct the immunomodulatory and osteogenic microenvironment for three dimension (3D) regeneration of bone tissues. 3D scaffolds, with various chemical composition, macroporous structure and surface characteristics offer a beneficial microenvironment for bone tissue regeneration. However, there is a gap between the well-ordered surface microstructure of bioceramic scaffolds and immune microenvironment for bone regeneration. In this study, a gear-inspired 3D scaffold with well-ordered surface microstructure was successfully prepared through a modified extrusion-based 3D printing strategy for immunomodulation and bone regeneration. The prepared gear-inspired scaffolds could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. The subsequent in vivo study demonstrated that the gear-inspired scaffolds were able to attenuate inflammation and further promote new bone formation. The study develops a facile strategy to construct well-ordered surface microstructure which plays a key role in 3D immunomodulatory and osteogenic microenvironment for bone tissue engineering and regenerative medicine. • A gear-inspired 3D bioceramic scaffold with highly well-ordered surface microstructure was successfully fabricated through a modified extrusion-based 3D printing technique. • The size and shape of the highly well-ordered microstructure could be readily modulated. • Taking advantage of good inducing effect of the well-ordered microstructure, the gear-inspired scaffold could be used as a satisfactory biomaterial, which could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. • The gear-inspired scaffold could construct 3D immunomodulatory microenvironment to significantly attenuate inflammation and further promote new bone formation in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) is the main inorganic component of human bone. Inspired by nacre and cortical bone, hydroxyapatite-based coil scaffolds were successfully prepared. The scaffolds presented "brick and mortar" multi-layered structure of nacre and multi-layered concentric circular structure of cortical bone. Because of bioactive components and hierarchical structure, the scaffolds possessed good compressive strength (≈95 MPa), flexural strength (≈161 MPa) and toughness (≈1.1 MJ/m3). In addition, they showed improved angiogenesis and osteogenesis in rat and rabbit critical sized bone defect models. By mimicking co-biological systems, this work provided a feasible strategy to optimize the properties of traditional tissue engineering biological materials for vascularized bone regeneration. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Owing to the different biological properties of articular cartilage and subchondral bone, it remains significant challenge to construct a bi-lineage constructive scaffold. In this study, manganese (Mn)-doped β-TCP (Mn-TCP) scaffolds with varied Mn contents are prepared by a 3D-printing technology. The effects of Mn on the physicochemical properties, bioactivity, and corresponding mechanism for stimulating osteochondral regeneration are systematically investigated. The incorporation of Mn into β-TCP lowers the lattices parameters and crystallization temperatures, but improves the scaffold density and compressive strength. The ionic products from Mn-TCP significantly improve the proliferation of both rabbit chondrocytes and mesenchymal stem cells (rBMSCs), as well as promote the differentiation of chondrocytes and rBMSCs. The in vivo study shows that Mn-TCP scaffolds distinctly improve the regeneration of subchondral bone and cartilage tissues as compared to TCP scaffolds, upon transplantation in rabbit osteochondral defects for 8 and 12 weeks. The mechanism is closely related to the Mn2+ ions significantly stimulated the proliferation and differentiation of chondrocytes through activating HIF pathway and protected chondrocytes from the inflammatory osteoarthritis environment by activating autophagy. These findings suggest that 3D-printing of Mn-containing scaffolds with improved physicochemical properties and bilineage bioactivities represents an intelligent strategy for regenerating osteochondral defects. [ABSTRACT FROM AUTHOR]

Adv. Funct. Mater.2017, 27, 1703117 DOI: 10.1002/adfm.201703117 The above article, first published online on 31 July 2017 in Wiley Online Library (https://doi.org/10.1002/adfm.201703117) and corrected on 19 March 2019 (https://doi.org/10.1002/adfm.201900376) has been retracted by agreement with the authors, the journal Editor‐in‐Chief, and Wiley‐VCH Verlag GmbH & Co. KGaA. The retraction has been agreed upon due to several flawed figures as published in the article, containing duplicate images, which calls the validity of these data into question. Reference C. Deng, Q. Yao, C. Feng, J. Li, L. Wang, G. Cheng, M. Shi, L. Chen, J. Chang, C. Wu, Adv. Funct. Mater.2017, 27, 1703117. [ABSTRACT FROM AUTHOR]

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. Micro/nanostructured surfaces in bredigite scaffolds are successfully prepared via a hydrothermal process. In vitro, the micro/nanostructured surface significantly promotes differentiation of chondrocytes by activating integrins α5β1 and αvβ1, and stimulates osteogenic differentiation of rabbit bone marrow stromal cells through the synergetic effects of integrin α5β1 and RhoA. Furthermore, the micro/nanostructured surface possesses dual physiological functions for the regeneration of both cartilage and subchondral bone. [ABSTRACT FROM AUTHOR]

3D-printed scaffolds have been developed as potential therapeutic strategies in bone tissue engineering. Mg/PCL biomaterials have been attracted much attention owing to biocompatibility, biodegradability as well as tunable mechanical properties. In this work, we developed 3D-printed customized Mg/PCL composite scaffolds with enhanced osteogenesis and biomineralization. Mg microparticles embedded in PCL-based scaffolds took a positive role in the improvement of biocompatibility, biomineralization, and biodegradable abilities. When incorporated with 3 wt% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that 3 Mg/PCL scaffolds had improved mechanical properties, good biocompatibility, enhanced osteogenic and angiogenic activities. Besides, the in vivo studies demonstrated that Mg/PCL scaffolds promoted tissue ingrowth and new bone formation. In sum, these findings indicated that 3D-printed cell-free Mg/PCL scaffolds are promising strategies for bone healing application. [Display omitted] • 3D-printed Mg/PCL scaffolds were developed as a promising approach for bone healing. • Mg/PCL scaffolds exhibited tunable mechanical properties and enhanced hydrophilicity. • 3 Mg/PCL scaffolds displayed good biocompatibility, enhanced osteogenic and angiogenic activities. • 3 Mg/PCL scaffolds promoted tissue ingrowth and new bone formation. • Mg in PCL scaffolds had positive effects on the improvement of biomineralization, and biodegradability. [ABSTRACT FROM AUTHOR]

Osteochondral defects are characterized by damage to both articular cartilage and subchondral bone. Various tissue engineering strategies have been developed for osteochondral defect repair. However, strong mechanical properties and dual-lineage (osteogenesis and chondrogenesis) bioactivity still pose challenges for current biomaterial design. Silicate nanoclay has been reported to improve the mechanical properties and biofunctionality of polymer systems, but its effect on in vitro dual-lineage differentiation or in vivo osteochondral regeneration has not been extensively investigated before. Here, a novel enzymatically crosslinked silk fibroin (SF)-Laponite (LAP) nanocomposite hydrogel was fabricated and evaluated for osteochondral regeneration. The incorporation of a small amount of LAP (1% w/v) accelerated the gelation process of SF and greatly enhanced the mechanical properties and hydrophilicity of the hydrogel. In vitro investigations showed that the developed SF-LAP hydrogel was biocompatible and was able to induce osteogenic and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), validated by Alizarin red/Alcian blue staining, qPCR, and immunofluorescent staining. During an 8-week implantation into rabbit full-thickness osteochondral defects, the SF-LAP hydrogel promoted the simultaneous and enhanced regeneration of cartilage and subchondral bone. The repaired tissue in the chondral region was constituted mainly of hyaline cartilage with typical chondrocyte morphology and cartilaginous extracellular matrix (ECM). These findings suggested that the SF-LAP nanocomposite hydrogel developed in this study served as a promising biomaterial for osteochondral regeneration due to its mechanical reinforcement and dual-lineage bioactivity. [Display omitted] • A novel enzymatically crosslinked SF-LAP nanocomposite hydrogel was prepared. • The incorporation of LAP enhanced its mechanical properties and hydrophilicity. • The SF-LAP hydrogel promoted osteogenic and chondrogenic differentiation of BMSCs. • The SF-LAP hydrogel promoted the regeneration of cartilage and subchondral bone. [ABSTRACT FROM AUTHOR]