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The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between ex-vivo cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.

Due to the specific structure of natural bone, most of the therapeutics are incapable to be delivered into the targeted site with effective concentrations. Nanotechnology has provided a good way to improve this issue, cell membrane mimetic nanoparticles (NPs) have been emerging as an ideal nanomaterial which integrates the advantages of natural cell membranes with synthetic NPs to significantly improve the biocompatibility as well as achieving long-lasting circulation and targeted delivery. In addition, functionalized modifications of the cell membrane facilitate more precise targeting and therapy. Here, an overview of the preparation of cell membrane-coated NPs and the properties of cell membranes from different cell sources has been given to expatiate their function and potential applications. Strategies for functionalized modification of cell membranes are also briefly described. The application of cell membrane-coated NPs for bone therapy is then presented according to the function of cell membranes. Moreover, the prospects and challenges of cell membrane-coated NPs for translational medicine have also been discussed.

The skeletal system is responsible for weight-bearing, organ protection, and movement. Bone diseases caused by trauma, infection, and aging can seriously affect a patient's quality of life. Bone targeted biomaterials are suitable for the treatment of bone diseases. Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects. A large number of bone-targeted micro-nano materials have been developed. However, only a few studies addressed bone-targeted hydrogel. The large size of hydrogel makes it difficult to achieve systematic targeting. However, local targeted hydrogel still has significant prospects. Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel. Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel. Besides, injectable hydrogel drug depot carrying bone-targeted drugs is another strategy. In this review, we summarize the bone-targeted hydrogel through application environment, construction strategies and disease applications. We hope this article will provide a reference for the development of bone-targeted hydrogels. We also hope this article could increase awareness of bone-targeted materials.

Skeletal muscle disorders have posed great threats to health. Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging. Aptamers can improve targeting efficacy. In this study, for the first time, the human skeletal muscle-specific ssDNA aptamers (HSM01, etc.) were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells

Background Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy. Purpose In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA. Materials and methods AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo. Results The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds. Conclusion The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.

Bone defects repair and regeneration by various causes such as tumor resection, trauma, degeneration, etc. have always been a key issue in the clinics. As one of the few organs that can regenerate after adulthood, bone itself has a strong regenerative ability. In recent decades, bone tissue engineering technology provides various types of functional scaffold materials and seed cells for bone regeneration and repair, which significantly accelerates the speed and quality of bone regeneration, and many clinical problems are gradually solved. However, the bone metabolism mechanism is complicated, the research duration is long and difficult, which significantly restricts the progress of bone regeneration and repair research. Organoids as a new concept, which is built in vitro with the help of tissue engineering technology based on biological theory, can simulate the complex biological functions of organs in vivo. Once proposed, it shows broad application prospects in the research of organ development, drug screening, mechanism study, and so on. As a complex and special organ, bone organoid construction itself is quite challenging. This review will introduce the characteristics of bone microenvironment, the concept of organoids, focus on the research progress of bone organoids, and propose the strategies for bone organoid construction, study direction, and application prospects.

Nanosized extracellular vesicles derived from bacteria contain diverse cargo and transfer intercellular bioactive molecules to cells. Due to their favorable intercellular interactions, cell membrane-derived bacterial extracellular vesicles (BEVs) have great potential to become novel drug delivery platforms. In this review, we summarize the biogenesis mechanism and compositions of various BEVs. In addition, an overview of effective isolation and purification techniques of BEVs is provided. In particular, we focus on the application of BEVs as bioactive nanocarriers for drug delivery. Finally, we summarize the advances and challenges of BEVs after providing a comprehensive discussion in each section. We believe that a deeper understanding of BEVs will open new avenues for their exploitation in drug delivery applications.

Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed.

Implant failure caused by unsatisfying osseointegration is still a noteworthy clinical problem. Strontium (Sr) has been confirmed to be a bioactive element that facilitates bone growth. In this study, Sr was surface incorporated in titanium (Ti) implant with different contents. The XRD results demonstrated that Sr existed mainly in the form of SrTiO

Yolk-shell magnetic mesoporous microspheres exhibit potential applications in biomedicine, bioseparation, and catalysis. Most previous reports focus on establishing various interface assembly strategies to construct yolk-shell mesoporous structures, while little work has been done to control their surface topology and study their relevant applications. Herein, a unique kind of broccoli-like yolk-shell magnetic mesoporous silica (YS-BMM) microsphere is fabricated through a surfactant-free kinetic controlled interface assembly strategy. The obtained YS-BMM microspheres possess a well-defined structure consisting of a magnetic core, middle void, mesoporous silica shell with tunable surface roughness, large superparamagnetism (36.4 emu g-1 ), high specific surface area (174 m2 g-1 ), and large mesopores of 10.9 nm. Thanks to these merits and properties, the YS-BMM microspheres are demonstrated to be an ideal support for immobilization of ultrafine Pt nanoparticles (≈3.7 nm) and serve as superior nanocatalysts for hydrogenation of 4-nitrophenol with yield of over 90% and good magnetic recyclability. Furthermore, YS-BMM microspheres show excellent biocompatibility and can be easily phagocytosed by osteoclasts, revealing a potential candidate in sustained drug release in orthopedic disease therapy.

Pathological angiogenesis is driven by uncontrolled growth of endothelial cells (ECs), which could lead to retinopathy, tumor and rheumatoid arthritis, etc. ECs must experience multiple cell division process to grow, and cytokinesis is the final step. The present study shows that PEGylated GNRs (PEG-GNRs) specifically target ECs cytokinesis process which results in high ratio of binucleated cells, and these binucleated ECs lose the ability to proliferate. Further data show that PEG-GNRs do not induce toxicity in vitro and in vivo. PEG-GNRs could inhibit ECs proliferation, migration, tube formation and inhibit angiogenesis in ex vivo model. Oxygen induced retinopathy and tumor angiogenesis model further show that PEG-GNRs can inhibit angiogenesis in vivo. Gene expression profiles reveal that PEG-GNRs mainly affect ECs cell division process, and PEG-GNRs treated ECs are arrested in G2/M phase. The mechanism is that PEG-GNRs could disrupt TGFβ pathway, and subsequently suppress the assembly of actin filaments in contractile ring site. These findings indicate that PEG-GNR is a novel cytokinesis inhibitor which can be used to interfere with retinal angiogenesis and tumor.

Yun Gyeong Kang,1 Jie Wei,2 Ji Won Shin,1 Yan Ru Wu,3 Jiacan Su,4 Young Shik Park,5 Jung-Woog Shin1,3,6 1School of Biomedical Engineering, Inje University, Gimhae, Republic of Korea; 2Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China; 3Department of Health Science and Technology, Inje University, Gimhae, Republic of Korea; 4Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China; 5School of Biological Science, Inje University, Gimhae, Republic of Korea; 6Cardiovascular and Metabolic Disease Center/Institute of Aged Life Redesign/UHARC, Inje University, Gimhae, Republic of Korea Background: Successful bone tissue engineering using scaffolds is primarily dependent on the properties of the scaffold, including biocompatibility, highly interconnected porosity, and mechanical integrity. Methods: In this study, we propose new composite scaffolds consisting of mesoporous magnesium silicate (m_MS), polycaprolactone (PCL), and wheat protein (WP) manufactured by a rapid prototyping technique to provide a micro/macro porous structure. Experimental groups were set based on the component ratio: (1) WP0% (m_MS:PCL:WP =30:70:0 weight per weight; w/w); (2) WP15% (m_MS:PCL:WP =30:55:15 w/w); (3) WP30% (m_MS:PCL:WP =30:40:30 w/w). Results: Evaluation of the properties of fabricated scaffolds indicated that increasing the amount of WP improved the surface hydrophilicity and biodegradability of m_MS/PCL/WP composites, while reducing the mechanical strength. Moreover, experiments were performed to confirm the biocompatibility and osteogenic differentiation of human mesenchymal stem cells (MSCs) according to the component ratio of the scaffold. The results confirmed that the content of WP affects proliferation and osteogenic differentiation of MSCs. Based on the last day of the experiment, ie, the 14th day, the proliferation based on the amount of DNA was the best in the WP30% group, but all of the markers measured by PCR were the most expressed in the WP15% group. Conclusion: These results suggest that the m_MS/PCL/WP composite is a promising candidate for use as a scaffold in cell-based bone regeneration. Keywords: mesoporous magnesium silicate, wheat protein, scaffold, bone tissue engineering, osteogenic differentiation&nbsp

In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH=7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration.

Liehu Cao,1,* Weizong Weng,1,* Xiao Chen,1,* Jun Zhang,1 Qirong Zhou,1 Jin Cui,1 Yuechao Zhao,1 Jung-Woog Shin,2 Jiacan Su1 1Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea *These authors contributed equally to this work Abstract: Nanoporous lithium doping magnesium silicate (nl-MS) was introduced into calcium sulfate hemihydrate to prepare calcium sulfate composite (nl-MSC) bone cements. The introduction of nl-MS improved the in vitro degradability of nl-MSC cements, which could neutralize acidic degradable products of calcium sulfate and prevented the pH from dropping. The cements were implanted into the bone defects of femur bone of rabbits, and the results of histological and immunohistochemical analysis revealed that massive new bone tissue formed in the defects while the cements were degradable, indicating that the osteogenesis and degradability of the nl-MSC cements were much better than the control calcium sulfate dihydrate (CSD) cements. Furthermore, the positive expression of vascular endothelial growth factor and collagen type I for nl-MSC cements was higher than CSD, indicating that addition of nl-MS into the cements enhanced vascularization and osteogenic differentiation. The results suggested that the nl-MSC cements with good biocompatibility and degradability could promote vascularization and osteogenesis, and had great potential to treat bone defects. Keywords: bone cements, nanoporous lithium doping magnesium silicate, degradability, vascularization, osteogenesis

Jun Hou,1 Donghui Fan,2 Lingming Zhao,2 Baoqin Yu,3 Jiacan Su,3 Jie Wei,2 Jung-Woog Shin4 1The First Affiliated Hospital of Anhui Medical University, Department of Oral and Maxillofacial Surgery, Hefei, 2Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 3Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea Abstract: Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(ε-caprolactone)–poly(ethyleneglycol)–poly(ε-caprolactone) (PCL–PEG–PCL). The results revealed that the addition of n-BD into PCL–PEG–PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL–PEG–PCL composite (n-BPC) compared with PCL–PEG–PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL–PEG–PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL–PEG–PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair. Keywords: nanobredigite, PCL–PEG–PCL, biocomposite scaffolds, degradability, osteo­genesis

Absorbable polyelectrolyte complexes-based hemostats are promising for controlling hemorrhage in iatrogenic injuries during surgery, whereas their hemostatic efficacy and other performances require further improvement for clinical application. Herein, spherical mesoporous bioglass nanoparticles (mBGN) were fabricated, and mBGN-polyelectrolyte complexes (composed of carboxymethyl starch and chitosan oligosaccharide) nanocomposites (BGN/PEC) with different mBGN contents were prepared via in situ coprecipitation followed by lyophilization. The effect of various mBGN content (10 and 20 wt%) on morphology, zeta potential, water absorption, degradation behavior and ion release were systematically evaluated. The in vitro degradability was dramatically promoted and a more neutral environment was achieved with the incorporation of mBGN, which is preferable for surgical applications. The in vitro coagulation test with whole blood demonstrated that the incorporation of mBGN facilitated blood clotting process. The plasma coagulation evaluation indicated that BGN/PEC had increased capability to accelerate coagulation cascade via the intrinsic pathway than that of the PEC, while have inapparent influence on the extrinsic and common pathway. The in vivo hemostatic evaluation in a rabbit hepatic hemorrhage model revealed that BGN/PEC with 10 wt% mBGN (10BGN/PEC) treatment group had the lowest blood loss, although its hemostatic time is close to that of 20BGN/PEC treatment group. The cytocompatibility evaluation with MC3T3-L1 fibroblasts indicated that 10BGN/PEC induced a ~25% increase of cell viability compared to the PEC at days 4 and 7, indicating improved biocompatibility. These findings support the promising application of absorbable BGN/PEC with optimized mBGN content as internal hemostats and present a platform for further development of PEC-based hemostats.

Zhaoying Wu,1 Quan Li,2 Yongkang Pan,1 Yuan Yao,1 Songchao Tang,1 Jiacan Su,2 Jung-Woog Shin,3 Jie Wei,1 Jun Zhao4,5 1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, 2Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea; 4Department of Orthodontics, 5Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China Abstract: Bioactive composite macroporous scaffold containing nanoporosity was prepared by incorporation of nanoporous magnesium silicate (NMS) into poly(butylene succinate) (PBSu) using solvent casting–particulate leaching method. The results showed that the water absorption and in vitro degradability of NMS/PBSu composite (NMPC) scaffold significantly improved compared with magnesium silicate (MS)/PBSu composite (MPC) scaffold. In addition, the NMPC scaffold showed improved apatite mineralization ability, indicating better bioactivity, as the NMPC containing nanoporosity could induce more apatite and homogeneous apatite layer on the surfaces than MPC scaffold. The attachment and proliferation of MC3T3-E1 cells on NMPC scaffold increased significantly compared with MPC scaffold, and the alkaline phosphatase (ALP) activity of the cells on NMPC scaffold was expressed at considerably higher levels compared with MPC scaffold. Moreover, NMPC scaffold with nanoporosity not only had large drug loading (vancomycin) but also exhibited drug sustained release. The results suggested that the incorporation of NMS into PBSu could produce bioactive composite scaffold with nanoporosity, which could enhance water absorption, degradability, apatite mineralization and drug sustained release and promote cell responses. Keywords: nanocomposite, degradability, apatite mineralization, cell behaviors, drug release

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Alumina is one of the most common and stable metal oxides in nature, which has been developed as a novel adsorbent in enrichment of biomolecules due to its excellent affinity to phosphor or amino groups. In this study, ordered mesoporous alumina (OMA) with interconnected mesopores and surface acidic property is synthesized through a solvent evaporation induced co-assembly process using poly(ethylene oxide)-b-polystyrene (PEO-b-PS) diblock copolymer as a template and aluminium acetylacetonate (Al(acac)3) as the aluminium source. The pore size (12.1–19.7 nm), pore window size (3.5–9.0 nm) and surface acidity (0.092–0.165 mmol g−1) can be precisely adjusted. The highly porous structure endows the OMA materials with high hemoglobin (Hb) immobilization capacity (170 mg g−1). The obtained Hb@OMA composite is used as an electrocatalyst of biosensor for convienet and fast detection of hydrogen peroxide (H2O2) with a low H2O2 detection limit of 1.7 × 10−8 m and a wide linear range of 2.5 × 10−8 to 5.0 × 10−5 m. Moreover, the Hb@OMA sensors show a good performance in real time detection of H2O2 released from Homo sapiens bone osteosarcoma, indicating their potential application in complex biological processes. This work was supported by the NSF of China (51372041, 51422202, 21673048, 91749204 and 81771491), Shanghai Pujiang Program, China (No. 16PJ1401100), Key Basic Research Program of Science and Technology Commission of Shanghai Municipality (17JC1400100), Shanghai Municipal Science and Technology Commission Key Program (15411950600), Youth Top-notch Talent Support Program of China, the state key laboratory of Transducer Technology of China (Grant No. SKT1503), the Outstanding Talents Cultivation Program of Shanghai Health System (2017BR011), and Qatar University under GCC Co-Fund Program, Grant GCC-2017-001. The authors thank Prof. Guangrong Zhou for assistance in TEM characterization.

Mesoporous calcium sulfate-based bone cements (m-CSBC) were prepared by introducing mesoporous magnesium–calcium silicate (m-MCS) with specific surface area (410.9 m² g −1 ) and pore volume (0.8 cm³ g −1 ) into calcium sulfate hemihydrate (CSH). The setting time of the m-CSBC was longer with the increase of m-MCS content while compressive strength decreased. The degradation ratio of m-CSBC increased from 48.6 w% to 63.5 w% with an increase of m-MCS content after soaking in Tris–HCl solution for 84 days. Moreover, the m-CSBC containing m-MCS showed the ability to neutralize the acidic degradation products of calcium sulfate and prevent the pH from dropping. The apatite could be induced on m-CSBC surfaces after soaking in SBF for 7 days, indicating good bioactivity. The effects of the m-CSBC on vitamin D 3 sustained release behaviours were investigated. It was found that the cumulative release ratio of vitamin D 3 from the m-CSBC significantly increased with the increase of m-MCS content after soaking in PBS (pH = 7.4) for 25 days. The m-CSBC markedly improved the cell-positive responses, including the attachment, proliferation and differentiation of MC3T3-E1 cells, suggesting good cytocompatibility. Briefly, m-CSBC with good bioactivity, degradability and cytocompatibility might be an excellent biocement for bone regeneration.

Wenhua Song,1,* Xiangde Li,1,* Jun Qian,1 Guoyu Lv,2 Yonggang Yan,2 Jiacan Su,3 Jie Wei1 1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 2College of Physical Science and Technology, Sichuan University, Chengdu, People’sRepublic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this paper Abstract: Mesoporous calcium–silicon xerogels with a pore size of 15 nm (MCS-15) and pore volume of 1.43 cm3/g were synthesized by using 1,3,5-mesitylene (TMB) as the pore-expanding agent. The MCS-15 exhibited good degradability with the weight loss of 50 wt% after soaking in Tris-HCl solution for 56 days, which was higher than the 30 wt% loss shown by mesoporous calcium–silicon xerogels with a pore size of 4 nm (MCS-4). The pore size and pore volume of MCS-15 had significant influences on load and release of recombinant human bone morphogenetic protein-2 (rhBMP-2). The MCS-15 had a higher capacity to encapsulate a large amount of rhBMP-2; it could adsorb 45 mg/g of rhBMP-2 in phosphate-buffered saline after 24 hours, which was more than twice that with MCS-4 (20 mg/g). Moreover, the MCS-15 system exhibited sustained release of rhBMP-2 as compared with MCS-4 system (showing a burst release). The MCS-15/rhBMP-2 system could promote the proliferation and differentiation of human mesenchymal stem cells, showing good cytocompatibility and bioactivity. The results indicated that MCS-15, with larger mesopore size and higher pore volume, might be a promising carrier for loading and sustained release of rhBMP-2, which could be used as bone repair material with built-in osteoinduction function in bone reconstruction. Keywords: mesoporous calcium–silicon xerogels, pore size, pore volume, load-release, rhBMP-2

Wei Liang,1,* Yunfei Niu,2,* Shuhua Ge,1 Shaojun Song,2 Jiacan Su,2 Zhuojing Luo11Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: We report the synthesis of nanoapatite crystals via a hydrothermal reaction of hydroxyapatite precipitates. The impact of the reaction conditions on the properties of the crystals obtained were evaluated. The hydrothermal reaction that takes place markedly affected the crystallinity, morphology, and size of the nanoapatite crystals formed. High crystallinity and large crystal size were obtained at higher hydrothermal temperatures and longer hydrothermal reaction times. The nanoapatite crystals were needle-like when prepared under ambient pressure conditions and rod-like when prepared under increased pressure. The crystals prepared at ambient pressure had a larger aspect ratio compared with those prepared under increased pressure. The aging time of the initial hydroxyapatite precipitate significantly affected growth of the nanoapatite crystals. With other hydrothermal reaction conditions being equal, the fresh hydroxyapatite precipitate produced notably larger crystals than the aged hydroxyapatite precipitate. The influence of apatite morphology on osteoblast viability was studied by MTT assay. The results indicate that the rod-like apatite showed a better biological response than needle-like apatite in promoting cell growth. Transmission electron microscopy showed that large quantities of needle apatite entered into cells and damaged their morphology.Keywords: nanoapatite crystals, hydrothermal treatment, morphology, cell viability

Feng-Qian Li1, Cheng Yan2, Juan Bi1, Wei-Lin Lv3, Rui-Rui Ji3, Xu Chen1, Jia-Can Su3, Jin-Hong Hu31Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaAbstract: Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 µm to 8 µm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics.Keywords: scopolamine hydrobromide, chitosan, nanoparticles-in-microparticles system, spray-drying, orally disintegrating tablets

Ca-deficient hydroxyapatite (CDHA) porous scaffolds were successfully fabricated from calcium phosphate cement (CPC) by a particle-leaching method. The morphology, porosity and mechanical strength as well as degradation of the scaffolds were characterized. The results showed that the CDHA scaffolds with a porosity of 81% showed open macropores with pore sizes of 400-500mum. Thirty-six per cent of these CDHA scaffolds were degraded after 12 weeks in Tris-HCl solution. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the scaffolds, and the proliferation and differentiation of MSCs into osteoblastic phenotype were determined using MTT assay, alkaline phosphatase activity and scanning electron microscopy. The results revealed that the CDHA scaffolds were biocompatible and had no negative effects on the MSCs in vitro. The in vivo biocompatibility and osteogenicity of the scaffolds were investigated. Both CDHA scaffolds and MSC/scaffold constructs were implanted in rabbit mandibles and studied histologically. The results showed that CDHA scaffolds exhibited good biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into the scaffolds dramatically enhanced the efficiency of new bone formation, especially at the initial stage after implantation (from 2 to 4 weeks). However, the CDHA scaffolds showed as good biocompatibility and osteogenicity as the hybrid ones at 8 weeks. These results indicate that the CDHA scaffolds fulfill the basic requirements of bone tissue engineering scaffold.

Bioactive mesoporous diopside (m-DP) and poly( l -lactide) (PLLA) composite scaffolds with mesoporous/macroporous structure were prepared by the solution-casting and particulate-leaching method. The results demonstrated that the degradability and bioactivity of the mesoporous/macroporous scaffolds were significantly improved by incorporating m-DP into PLLA, and that the improvement was m-DP content-dependent. In addition, the scaffolds containing m-DP showed the ability to neutralize acidic degradation products and prevent the pH from dropping in the solution during the soaking period. Moreover, the scaffolds containing m-DP enhanced attachment, proliferation and alkaline phosphatase activity of MC3T3-E1 cells, which were also m-DP content-dependent. Furthermore, the histological and immunohistochemical analysis results showed that the scaffolds with m-DP significantly promoted new bone formation and improved the materials degraded in vivo , indicating good biocompatibility. The results suggested that the mesoporous/macroporous scaffolds of the m-DP/PLLA composite with osteogenesis had a potential for bone regeneration.

Zhiwei Wang,* Ming Li,* Baoqing Yu, Liehu Cao, Qingsong Yang, Jiacan SuDepartment of Orthopedics, Shanghai Hospital, Second Military Medical University, Shanghai, People's Republic of China *These authors contributed equally to this workAbstract: A bioactive composite of nano calcium-deficient apatite (n-CDAP) with an atom molar ratio of calcium to phosphate (Ca/P) of 1.50 and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) was synthesized, and a composite scaffold was fabricated. The composite scaffolds with 40 wt% n-CDAP contained well interconnected macropores around 400 µm, and exhibited a porosity of 75%. The weight-loss ratio of the n-CDAP/PCL–PEG–PCL was significantly greater than nano hydroxyapatite (n-HA, Ca/P = 1.67)/PCL–PEG–PCL composite scaffolds during soaking into phosphate-buffered saline (pH 7.4) for 70 days, indicating that n-CDAP-based composite had good degradability compared with n-HA. The viability ratio of MG-63 cells was significantly higher on n-CDAP than n-HA-based composite scaffolds at 3 and 5 days. In addition, the alkaline phosphatase activity of the MG-63 cells cultured on n-CDAP was higher than n-HA-based composite scaffolds at 7 days. Histological evaluation showed that the introduction of n-CDAP into PCL–PEG–PCL enhanced the efficiency of new bone formation when the composite scaffolds were implanted into rabbit bone defects. The results suggested that the n-CDAP-based composite exhibits good biocompatibility, biodegradation, and osteogenesis in vivo.Keywords: nano calcium-deficient apatite, composite scaffold, degradability, cell responses, osteogenesis

Jiacan Su, Liehu Cao, Baoqing Yu, Shaojun Song, Xinwei Liu, Zhiwei Wang, Ming LiDepartment of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, ChinaAbstract: A bone-implanted porous scaffold of mesoporous bioglass/polyamide composite (m-BPC) was fabricated, and its biological properties were investigated. The results indicate that the m-BPC scaffold contained open and interconnected macropores ranging 400–500 µm, and exhibited a porosity of 76%. The attachment ratio of MG-63 cells on m-BPC was higher than polyamide scaffolds at 4 hours, and the cells with normal phenotype extended well when cultured with m-BPC and polyamide scaffolds. When the m-BPC scaffolds were implanted into bone defects of rabbit thighbone, histological evaluation confirmed that the m-BPC scaffolds exhibited excellent biocompatibility and osteoconductivity, and more effective osteogenesis than the polyamide scaffolds in vivo. The results indicate that the m-BPC scaffolds improved the efficiency of new bone regeneration and, thus, have clinical potential for bone repair.Keywords: mesoporous bioglass, polyamide, composite scaffolds, biocompatibility, bone repair

Novel injectable and degradable calcium-magnesium phosphate cement (CMPC) with rapid-setting characteristic was developed by the introduction of magnesium phosphate cement (MPC) into calcium phosphate cement (CPC). The calcium-magnesium phosphate cement prepared under the optimum P/L ratio exhibited good injectability and desired workability. It could set within 10 min at 37 degrees C in 100% relative humidity and the compressive strength could reach 47 MPa after setting for 48 h, indicating that the prepared cement has relatively high initial mechanical strength. The results of in vitro degradation experiments demonstrated the good degradability of the injectable CMPC, and its degradation rate occurred significantly faster than that of pure CPC in simulated body fluid (SBF) solution. It can be concluded that the novel injectable calcium-magnesium phosphate cement is highly promising for a wide variety of clinical applications, especially for the development of minimally invasive techniques.