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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/m 3 ). 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., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr 5 (PO 4 ) 2 SiO 4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro . The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo . Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

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]

The treatment of osteochondral defects remains a huge challenge in clinic. The thermotherapy in traditional Chinese medicine is widely used in treating joint disease because the mild heat stimulation can promote the nutrient circulation. Inspired by the function of thermotherapy, we design a new thermotherapy strategy by using black bioceramic scaffolds to build local mild hyperthermal environment for treating osteochondral defects. Herein, black akermanite (B-AKT) bioceramic scaffolds with micro/nano surface structure and excellent photothermal conversion property are successfully fabricated. The temperature of scaffolds can be precisely controlled by near infrared (NIR) irradiation to construct a mild hyperthermal environment (～41°C). The micro/nanostructure on the scaffolds surface well promoted the cell adhesion and nutrition absorption by activating integrins and focal adhesion kinase (FAK). Meanwhile, the mild hyperthermal environment constructed by B-AKT scaffolds can simultaneously induce the chondrogenesis and osteogenesis both in vitro and in vivo by activating the expression of cellular heat shock proteins (HSPs) and corresponding signaling pathways. Furthermore, in rabbit osteochondral defects, mild hyperthermal environment induced by B-AKT scaffolds exhibits stimulatory effects on the integrated regeneration of cartilage and bone. This study proposes a novel therapy strategy of constructing local mild hyperthermal environment by black bioceramic scaffolds to treat osteochondral defects and other joint diseases. [Display omitted] • The black bioceramic scaffolds with surface micro/nano structure and photothermal properties. • The micro/nano surface structure could promote the cells adhesion and nutrition adsorption. • The mild hyperthermal environment was proved to enhance cells differentiation in vitro and repair osteochondral defects in vivo. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D)-printed scaffolds are widely used in tissue engineering to help regenerate critical-sized bone defects. However, conventional scaffolds possess relatively simple porous structures that limit the delivery of oxygen and nutrients to cells, leading to insufficient bone regeneration. Accordingly, in the present study, perfusable and permeable polycaprolactone scaffolds with highly interconnected hollow-pipe structures that mimic natural micro-vascular networks are prepared by an indirect one-pot 3D-printing method. In vitro experiments demonstrate that hollow-pipe-structured (HPS) scaffolds promote cell attachment, proliferation, osteogenesis and angiogenesis compared to the normal non-hollow-pipe-structured scaffolds. Furthermore, in vivo studies reveal that HPS scaffolds enhance bone regeneration and vascularization in rabbit bone defects, as observed at 8 and 12 weeks, respectively. Thus, the fabricated HPS scaffolds are promising candidates for the repair of critical-sized bone defects. [ABSTRACT FROM AUTHOR]

The significant guiding roles of nerves in bone formation and remodeling have been largely overlooked during the past decades when it comes to designing bone regeneration scaffolds. The requirement of intrabony nerve regeneration cannot be fulfilled by current therapeutic options, resulting in delayed innervation. Constructing a bone organoid which takes intrabony nerves into account can be a feasible approach. Herein, in combination with the nanocomposite bioinks and multicellular 3D bioprinting technology, a biomimetic neural-bone construct was successfully developed for innervated bone regeneration. Neural cells and bone-related cells were orderly printed to imitate the simplified spatial distribution of bone and nerves. Besides, inorganic calcium silicate (CS) nanowires were synthesized and incorporated into the bioinks to serve as "bioactive factors" to regulate multicellular behaviors. CS nanowires containing-bioinks could obviously promote the long-term survival and spreading as well as osteogenic and neurogenic differentiation of encapsulated cells. Furthermore, the in vivo results demonstrated that the CS nanowires containing-bioinks for 3D bioprinting of neural-bone constructs could simultaneously accelerate the new bone formation and ingrowth of nerve fibers. Taken together, this study offers a new concept by using inorganic nanomaterials as the bioactive components of bioinks for complex tissue regeneration, which represents a potential strategy for the fabrication of bone organoid with enhanced restoration of innervation and innervated bone tissues. A biomimetic neural-bone construct with the incorporation of inorganic calcium silicate nanowires is developed via multicellular 3D bioprinting technology, which can simultaneously promote innervation and bone regeneration. This study provides a potential strategy by using inorganic nanomaterials as the bioactive components for the fabrication of bone organoid with enhanced restoration of innervation and innervated bone tissues. [Display omitted] • Biomimetic neural-bone construct was developed for innervated bone regeneration by using 3D bioprinting technology. • Inorganic calcium silicate nanowires-based bioinks could simultaneously stimulating osteogenesis and neurogenesis. • 3D bioprinted construct with silicate biomaterials was a promising strategy for regeneration of innervated complex tissues. [ABSTRACT FROM AUTHOR]

Morbidity of osteoporosis is increasing as the world population grows and ages, but bone mineral density (BMD) as a common-used diagnostic indicator is not omnipotent in predicting the bone fragility. According to the definition of osteoporosis by World Health Organization (WHO), the present hypothesis proposes an additional fractal-dimension indicator less than 3 to measure the structural change of bones, and further to diagnose osteoporotic patients with complications, to which BMD is insensitive. Literature reports support that the fractal dimension is more sensitive than BMD in specific cases. The hypothesis shows a promise not only in improving the accuracy of screening osteoporotic patients as a complementary indicator to BMD, but also in evaluating mechanical properties of osteoporotic bone and bone-repair effect of bone tissue engineering. [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]

In article number 1807356, Yishen Zhu, Qingqiang Yao, and co‐workers develop a strategy to molecularly functionalize the self‐assembling peptide hydrogel (SAPH) FEFEFKFK onto 3D‐printed polycaprolactone (PCL) scaffolds, forming a reliable and stable coating layer. The prepared SAPH‐coated PCL scaffolds provide a superior performance for the regeneration of cartilage and subchondral bone simultaneously, offering a flexible strategy for osteochondral defects caused by osteoarthritis or acute trauma. [ABSTRACT FROM AUTHOR]

Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair. The molecularly functionalized self‐assembling peptide hydrogel‐coated polycaprolactone scaffolds provide superior performance for the regeneration of cartilage and subchondral bone simultaneously, offering a reliable and flexible strategy for osteochondral defects caused by osteoarthritis or acute trauma. [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]

• A TA-mediated E7/P15 peptide-functionalized Ca-alginate scaffold was prepared. • TA prime-coating improved scaffold stability and mechanical properties. • TA prime-coating enhanced peptide conjugation and sustained peptide release. • The scaffold induced BMSC recruitment and bi-lineage differentiation by E7 and P15. • The scaffold simultaneously enhanced cartilage and subchondral bone regeneration. The development of cell-instructive scaffolds, which provide biochemical cues to direct endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior, has the potential to revolutionize osteochondral tissue engineering. However, scaffold material itself is generally lacking the inductive signals. Here, a novel peptide-functionalized scaffold was prepared by prime-coating Ca-alginate scaffold with tannic acid (TA) followed by conjugation of E7/P15 peptides (CA-TA-E7/P15). The system leveraged TA as a reactive intermediate between Ca-alginate and peptides due to the multiple functional groups of TA. These interactions induced by TA prime-coating contributed to enhanced scaffold stability and mechanical properties, increased peptide conjugation and sustained release of peptides without affecting their bioactivity, in a TA concentration-dependent manner. The conjugation of E7/P15 peptides endowed the scaffold with the potential to enhance BMSCs recruitment and deposition of cartilage and bone extracellular matrix (ECM). Furthermore, the prepared CA-TA-E7/P15 scaffold showed a promoted biological performance of simultaneous cartilage and subchondral bone regeneration in rabbit osteochondral defect model. These findings indicate that TA is an effective surface modification intermediate and crosslinking aid, and that the CA-TA-E7/P15 scaffold developed in this study serves as a promising cell-instructive scaffold for osteochondral regeneration. [ABSTRACT FROM AUTHOR]