3D printing of hybrid biomaterials for bone tissue engineering: Calcium-polyphosphate microparticles encapsulated by polycaprolactone. Neufurth Meik,Wang Xiaohong,Wang Shunfeng,Steffen Renate,Ackermann Maximilian,Haep Natalie D,Schröder Heinz C,Müller Werner E G Acta biomaterialia Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca and the physiological inorganic polymer, polyphosphate (polyP). Those MP had been fortified by mixing with poly-ε-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100 °C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 µm and a stacked architecture leaving ≈0.5 mm-sized open holes enabling cell migration. The printed composite scaffold turned out to combine suitable biomechanical properties (Young's modulus of 1.60 ± 0.1 GPa; Martens hardness of 153 ± 28 MPa), matching those of cortical and trabecular bone, with morphogenetic activity. This scaffold was capable of attracting and promoting the growth of human bone-related SaOS-2 cells as demonstrated by staining for cell viability (Calcein AM), cell density (DRAQ5) and SEM studies. Furthermore, the hybrid material was demonstrated to upregulate the steady-state-expression of the cell migration-inducing chemokine SDF-1α. EDX analysis and FTIR measurements revealed the presence of hydroxyapatite in the mineral deposits formed on the scaffold surface. Based on the results we conclude that granular PCL/Ca-polyP-MP hybrid material is suitable for the fabrication of bioprintable scaffold which comprises not only biomechanical stability but also morphogenetic potential. STATEMENT OF SIGNIFICANCE:In present-day regenerative engineering efforts, biomaterial- and cell-based strategies are proposed that meet the required functional and spatial characteristics and variations, especially in the transition regions between soft (cartilage, tendon or ligament) and hard (bone) tissues. In a biomimetic approach we succeeded to fabricate amorphous Ca-polyP nanoparticles/microparticles which are highly biocompatible. Together with polycaprolactone (PCL), polyP can be bio-printed. This hybrid material attracts the cells, as documented optically as well as by a gene-expression studies. Since PCL is already a FDA-approved organic and inert polymer and polyP a physiological biologically active component this new bio-hybrid material has the potential to restore physiological functions, including bone remodelling and regeneration if used as implant. 10.1016/j.actbio.2017.09.031

Powder-based 3D printing for bone tissue engineering. Brunello G,Sivolella S,Meneghello R,Ferroni L,Gardin C,Piattelli A,Zavan B,Bressan E Biotechnology advances Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed. 10.1016/j.biotechadv.2016.03.009

3D-printed bioceramic scaffolds: From bone tissue engineering to tumor therapy. Ma Hongshi,Feng Chun,Chang Jiang,Wu Chengtie Acta biomaterialia Toward the aim of personalized treatment, three-dimensional (3D) printing technology has been widely used in bone tissue engineering owing to its advantage of a fast, precise, and controllable fabrication process. Conventional bioceramic scaffolds are mainly used for bone tissue engineering; however, there has been a significant change in the application of bioceramic scaffolds during the past several years. Therefore, this review focuses on 3D-printed bioceramic scaffolds with different compositions and hierarchical structures (macro, micro, and nano scales), and their effects on the mechanical, degradation, permeability, and biological properties. Further, this review highlights 3D-printed bioceramic scaffolds for applications extending from bone tissue regeneration to bone tumor therapy. This review emphasizes recent developments in functional 3D-printed bioceramic scaffolds with the ability to be used for both tumor therapy and bone tissue regeneration. Considering the challenges in bone tumor therapy, these functional bioceramic scaffolds have a great potential in repairing bone defects induced by surgery and kill the possibly residual tumor cells to achieve bone tumor therapy. Finally, a brief perspective regarding future directions in this field was also provided. The review not only gives a summary of the research developments in bioceramic science but also offers a new therapy strategy by extending multifunctions of traditional biomaterials toward a specific disease. STATEMENT OF SIGNIFICANCE:This review outlines the development tendency of 3D-printed bioceramic scaffolds for applications ranging from bone tissue regeneration to bone tumor therapy. Conventional bioceramic scaffolds are mainly used for bone tissue engineering; however, there has been a significant change in the application of bioceramic scaffolds during the past several years. Therefore, this review focuses on 3D-printed bioceramic scaffolds with different compositions and hierarchical structures (macro, micro, and nano scales), and their effects on the mechanical, degradation, permeability, and biological properties. Further, this review highlights 3D-printed bioceramic scaffolds for applications extending from bone tissue regeneration to bone tumor therapy. This review emphasizes recent developments in the functional 3D-printed bioceramic scaffolds with the ability to be used for both bone tumor therapy and bone tissue regeneration. 10.1016/j.actbio.2018.08.026

3D bioprinting of tissues and organs for regenerative medicine. Vijayavenkataraman Sanjairaj,Yan Wei-Cheng,Lu Wen Feng,Wang Chi-Hwa,Fuh Jerry Ying Hsi Advanced drug delivery reviews 3D bioprinting is a pioneering technology that enables fabrication of biomimetic, multiscale, multi-cellular tissues with highly complex tissue microenvironment, intricate cytoarchitecture, structure-function hierarchy, and tissue-specific compositional and mechanical heterogeneity. Given the huge demand for organ transplantation, coupled with limited organ donors, bioprinting is a potential technology that could solve this crisis of organ shortage by fabrication of fully-functional whole organs. Though organ bioprinting is a far-fetched goal, there has been a considerable and commendable progress in the field of bioprinting that could be used as transplantable tissues in regenerative medicine. This paper presents a first-time review of 3D bioprinting in regenerative medicine, where the current status and contemporary issues of 3D bioprinting pertaining to the eleven organ systems of the human body including skeletal, muscular, nervous, lymphatic, endocrine, reproductive, integumentary, respiratory, digestive, urinary, and circulatory systems were critically reviewed. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro drug testing models, and personalized medicine. While there is a substantial progress in the field of bioprinting in the recent past, there is still a long way to go to fully realize the translational potential of this technology. Computational studies for study of tissue growth or tissue fusion post-printing, improving the scalability of this technology to fabricate human-scale tissues, development of hybrid systems with integration of different bioprinting modalities, formulation of new bioinks with tuneable mechanical and rheological properties, mechanobiological studies on cell-bioink interaction, 4D bioprinting with smart (stimuli-responsive) hydrogels, and addressing the ethical, social, and regulatory issues concerning bioprinting are potential futuristic focus areas that would aid in successful clinical translation of this technology. 10.1016/j.addr.2018.07.004

Looking into the Future: Toward Advanced 3D Biomaterials for Stem-Cell-Based Regenerative Medicine. Liu Zhongmin,Tang Mingliang,Zhao Jinping,Chai Renjie,Kang Jiuhong Advanced materials (Deerfield Beach, Fla.) Stem-cell-based therapies have the potential to provide novel solutions for the treatment of a variety of diseases, but the main obstacles to such therapies lie in the uncontrolled differentiation and functional engraftment of implanted tissues. The physicochemical microenvironment controls the self-renewal and differentiation of stem cells, and the key step in mimicking the stem cell microenvironment is to construct a more physiologically relevant 3D culture system. Material-based 3D assemblies of stem cells facilitate the cellular interactions that promote morphogenesis and tissue organization in a similar manner to that which occurs during embryogenesis. Both natural and artificial materials can be used to create 3D scaffolds, and synthetic organic and inorganic porous materials are the two main kinds of artificial materials. Nanotechnology provides new opportunities to design novel advanced materials with special physicochemical properties for 3D stem cell culture and transplantation. Herein, the advances and advantages of 3D scaffold materials, especially with respect to stem-cell-based therapies, are first outlined. Second, the stem cell biology in 3D scaffold materials is reviewed. Third, the progress and basic principles of developing 3D scaffold materials for clinical applications in tissue engineering and regenerative medicine are reviewed. 10.1002/adma.201705388