Preparation and Performance of Three-Dimensional Silk FibroinScaffolds with Different Matrix Stiffness / 医用生物力学

Objective After hydrogen bonding between collagen ( COL) and silk fibroin ( SF ) at different concentrations, a composite scaffold with adjustable stiffness was prepared by combining with gel system, and its physical and chemical properties were characterized. Methods SF with different qualities was dissolved in sodium alginate (SA) solution, then COL solution at different concentration and calcium carbonate ( CaCO3 ) powder were added. The hydrogels of SC1, SC2, and SC3 groups were obtained by taking out the mixed solution and adding some gluconic acid lactone ( GDL) powder, and different SF scaffolds were obtained after freeze drying. Results The SF scaffolds with adjustable stiffness were successfully prepared. The compression moduli of SC1, SC2, and SC3 groups were (17. 31±2. 73), (24. 12±1. 81), (32. 54±1. 81) kPa, respectively. The innerstructure of the scaffolds was observed. From SC1 group to SC3 group, pores of the scaffolds were smaller and fewer, and hydrophilicity of the materials become better and better. Conclusions Three-dimensional ( 3D) porous scaffolds with different matrix stiffness can be prepared by changing the concentration of SF and COL solution. The concentration of SF and COL is proportional to the compression modulus, water absorption, water retention and swelling rate of SF scaffolds, while inversely proportional to porosity. The findings of this study are expected to provide theoretical guidance for construction of scaffolds with appropriate matrix stiffness for inducing osteogenic differentiation of mesenchymal stem cells

Progress of research on application of chondroitin sulfate in osteogenic repair materials / 口腔医学

@#Chondroitin sulfate is an important component of extracellular matrix (ECM) in animal and human body. In recent years, chondroitin sulfate has been proven to have potential efficacy in biomedical application and has been widely used in bone regeneration and osteogenesis, especially in craniofacial reconstruction and dental medicine. Research shows that chondroitin sulfate derivatives and chondroitin sulfate composite scaffolds have great potential in promoting osteogenesis and biomineralization. However, due to the variety of chondroitin sulfate and various application forms, study on its mechanism of osteogenic repair is still insufficient. In this paper, biological characteristics, bone regeneration and osteogenesis of chondroitin sulfate, its application in different biomaterial design and future prospect are discussed.

Efeitos do laser de baixa intensidade em osteoblastos cultivados em arcabouços nanofibrosos de ácido polilático / Effects of low-intensity laser on osteoblasts cultured on polylactic acid nanofibrous scaffolds

A engenharia de tecidos ósseos é um ramo importante da medicina regenerativa e envolve o desenvolvimento de arcabouços com composição e arquitetura favoráveis à integração celular, além do estudo de fatores capazes de promover a adesão e proliferação celular, incluindo estímulos químicos e biofísicos. O objetivo do estudo foi avaliar a utilização do laser de baixa intensidade (LBI) como uma ferramenta para promover a bioestimulação in vitro de células osteoblásticas cultivadas em arcabouços nanofibrosos de ácido polilático (PLA). Os arcabouços foram produzidos pela técnica de eletrofiação e caracterizados quanto à molhabilidade, composição pela espectroscopia no infravermelho por transformada de Fourier (FTIR), morfologia da superfície por microscópica eletrônica de varredura (MEV), caracterização termogravimétrica (TGA), calorimetria diferencial exploratória (DSC) e cristalinidade por difração de raios-X (DRX). Os ensaios biológicos foram conduzidos com osteoblastos da linhagem OFCOL II cultivados na superfície dos arcabouços e submetidos ou não (grupo controle) a irradiação com laser diodo InGaAIP na potência de 30 mW, nas doses de 1, 4 e 6 J/cm² e nos comprimentos de onda de 660 nm (grupos V1, V4, V6, respectivo as doses) e 780 nm (grupos I1, I4 e I6, respectivo as doses). Os efeitos do LBI na proliferação dos osteoblastos foram avaliados através do método bioquímico Alamar Blue, nos intervalos de 24, 48 e 72h, enquanto a viabilidade e a morfologia celular foram analisadas no intervalo de 72h, através do ensaio Live/Dead e da microscopia eletrônica de varredura (MEV), respectivamente. Os dados do ensaio bioquímico de Alamar Blue mostraram uma maior proliferação celular nos grupos V6 em todos os intervalos analíticos em comparação ao grupo controle (p<0,05). Outras diferenças entre o grupo controle e irradiados foram encontradas apenas nos intervalos de 48h e 72h para V1, e para o grupo IV6 em 72h. O ensaio Live/Dead revelou um aumento na viabilidade celular nos grupos trados com LBI, sendo significativamente maior no grupo V1 quando comparado ao grupo controle. A análise por MEV mostrou adequada interação dos osteoblastos aos arcabouços, com o corpo celular se espalhando ao longo do eixo da nanofibra e a presença de contatos físicos mais evidentes, através da formação de ligação por meio de filopódios e lamelipódios, nos grupos V1, V6 e I6. Em conjunto, os dados do presente trabalho mostraram que o LBI promove a bioestimulação de osteoblastos cultivados sobre nanofibras de PLA, o que aponta para o seu uso potencial nas técnicas de engenharia tecidual óssea, sobretudo no que se refere ao uso do comprimento de onda de 660 nm, a qual apresentou grupos com mais resultados significativos (AU).

Bone tissue engineering is a relevant branch of regenerative medicine and involves the development of scaffolds with composition and architecture favorable to cell integration, in addition to studying factors capable of promoting cell adhesion and proliferation, including chemical and biophysical stimuli. The study aimed to evaluate the use of low-level laser irradiation (LLLI) to promote in vitro biostimulation of osteoblastic cells cultured on polylactic acid (PLA) nanofibrous scaffolds. The scaffolds were produced by the electrospinning technique and characterized in terms of wettability, composition by Fourier transform infrared spectroscopy (FTIR), surface morphology by scanning electron microscopy (SEM), thermogravimetric characterization (TGA), differential scanning calorimetry (DSC) and crystallinity by Xray diffraction (XRD). The biological assays were conducted with osteoblasts of the OFCOL II lineage cultured on the surface of the scaffolds and submitted or not (control group) to irradiation with InGaAIP diode laser, power of 30 mW, with doses of 1, 4 and 6 J/cm² and wavelengths of 660 nm (groups V1, V4, V6, respectively doses) and 780 nm (groups I1, I4 and I6, respectively doses). The effects of LLLT from the perspective of osteoblasts were evaluated using the biochemical method Alamar Blue assay, at intervals of 24, 48 and 72h, while cell viability and morphology were observed at 72h, using the Live/Dead assay and electron microscopy. scan (SEM), respectively. The Alamar Blue assay data showed more significant cell proliferation in groups in the V6 groups at all analytical intervals compared to the control group (p<0.05). Other differences between the control and irradiated groups were found only at intervals of 48h and 72h for V1, and for group IV6 at 72h. The Live/Dead assay revealed an increase in cell viability in the groups treated with LLLT, being significantly higher in the V1 group when compared to the control group. SEM analysis showed adequate interaction between osteoblasts and scaffolds, with the cell body spreading along the nanofiber axis and the presence of more evident physical contacts, through the formation of bonds through filopodia and lamellipodia, in groups V1, V6 and I6. Together, the data from the present study observed that LLLT promotes the biostimulation of osteoblasts cultured on PLA nanofibers, which pointed to its potential use in bone tissue engineering techniques, especially with regard to the use of the wavelength of 660 nm, which presented groups with more significant results (AU).

3D spheroid cell cultures and their role in bone regeneration: a systematic review / Cultivos de esferoides 3D y su papel en la regeneración ósea: una revisión sistemática

Abstract Recently, the 3D spheroid cell culture application has been extensively used in the treatment of bone defects. A wide variety of methodologies have been used, which has made the comparison of results complex. Therefore, this systematic review has two aims: (i) to perform an analysis focused on the role of 3D spheroid cell culture in bone regeneration strategies; and (ii) address the main challenges in clinical application. A search of the following keywords "3D cell culture", "spheroid", and "bone regeneration" was carried out in the PubMed, Scopus, and ScienceDirect databases and limited to the years 2010-2020. Studies were included if their primary objective was the behavior of cell aggregates to formed spheroids structures by different 3D cell culture techniques focused on the regeneration of bone tissue. To address the risk of bias for in vitro studies, the United States national toxicology program tool was applied, and descriptive statistics of the data were performed, with the SPSS V.22 program. A total of 16 studies were included, which met the established criteria corresponding to in vitro and in vitro/in vivo studies; most of these studies used stem cells for the 3D cell spheroids. The most often methods used for the 3D formation were low adherence surface and rotational methods, moreover, mesenchymal stem cells were the cell line most frequently used because of their regenerative potential in the field of bone tissue engineering. Although the advances in research on the potential use of 3D spheroids in bone regeneration have made great strides, the constant innovation in cell spheroid formation methodologies means that clinical application remains in the future as strategy for 3D tissue bioprinting.

Resumen Recientemente, la aplicación del cultivo 3D de esferoides se ha utilizado ampliamente en el tratamiento de defectos óseos. La variedad de metodologías para lograr los cultivos 3D de esferoides ha hecho compleja la comparación de resultados. Por tanto, esta revisión sistemática tiene dos objetivos: (i) realizar un análisis centrado en el papel de los cultivos 3D de esferoides en las estrategias de regeneración ósea; y (ii) abordar los principales desafíos en la aplicación clínica. Se realizó una búsqueda de las siguientes palabras clave "cultivo celular 3D", "esferoide" y "regeneración ósea" en las bases de datos PubMed, Scopus y ScienceDirect y se limitó a los años 2010-2020. Se incluyeron los estudios si su principal objetivo era el comportamiento de agregados celulares para generar las estructuras esferoidales desarrollados por diferentes técnicas de cultivo celular 3D enfocadas a la regeneración del tejido óseo. Para abordar el riesgo de sesgo de los estudios in vitro, se aplicó la herramienta del programa nacional de toxicología de Estados Unidos y se realizaron estadísticas descriptivas de los datos, con el programa SPSS V.22. Se incluyeron un total de 16 estudios, que cumplieron con los criterios establecidos correspondientes a estudios in vitro e in vitro/in vivo; la mayoría de estos estudios utilizaron células troncales para generar los esferoides celulares 3D. Los métodos más utilizados para la formación de los esferoides 3D fueron la superficie de baja adherencia y los métodos de rotación, asimismo, la línea celular de células troncales mesenquimales fueron las más utilizadas debido a su gran potencial regenerativo en el campo de la ingeniería de tejidos óseos. Aunque los avances en la investigación sobre el uso potencial de los cultivos celulares de esferoides 3D en la regeneración ósea han logrado grandes avances, la constante innovación en las metodologías de la generación de esferoides 3D deja claro que la aplicación clínica de estos permanecerá en el futuro como estrategia en la bioimpresión tisular.

CircularRNA CDR1as promotes osteogenic differentiation and angiogenesis related genes expression in mouse bone marrow mesenchymal stem cells / 口腔疾病防治

Objective@# To investigate the effects of over expression and low expression of antisense transcripts of circular RNA cerebellar degeneration associated protein 1 (CDR1as) in Balb/C mouse bone marrow mesenchymal stem cells (BMSCs) on factors related to osteogenesis and angiogenesis.@*Methods@#BMSCs were cultured and identified in vitro. The lentiviral (LV) vector containing the overexpressed and silenced circRNA CDR1as genes and the control lentivirus were respectively transfected into mouse BMSCs, and stable cell lines were screened. The cells were divided into the circRNACDR1as over expression group and the over expression control group, and the CircRNACDR1as low expression group and the low expression control group. The components were stained with Alizarin Red S and alkaline phosphatase after 14 and 21 days of osteoinduction; qRT-PCR was used to detect the target genes circRNA CDR1as, osteogenic differentiation markers alkaline phosphatase (ALP), runt- related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN), osterix(Osx), collagen I (COL-1), and the mRNA expression levels of vascular endothelial grown factor (VEGF) and angiogenin-1 (Ang-1). @*Results@# The results of alizarin red staining and alkaline phosphatase staining showed that the extracellular matrix calcium precipitation and ALP staining area of the over expression experimental group was greater than its control group, and those of the low expression experimental group was less than its control group. As the number of days of osteogenic induction increased, the calcium precipitation and ALP staining in each group also increased. RT-PCR results showed that the mRNA expression levels of circRNA CDR1as, ALP, RUNX2, OCN, OPN, OSX, COL-1, VEGF and Ang-1 in the over expression experimental group BMSCs were significantly increased (P<0.001). In the low expression experimental group, the mRNA expression levels of circRNA CDR1as, ALP, RUNX2, OCN, OPN, OSX, COL-1, VEGF and Ang-1 in BMSCs were significantly reduced (P<0.001). @*Conclusion@# Over expression of the circRNA CDR1as gene promotes the osteogenic differentiation and angiogenesis of BMSCs. Low expression of the circRNA CDR1as gene inhibits the osteogenic differentiation and angiogenesis of BMSCs.

Therapeutic effects of percutaneous vertebroplasty and kyphoplasty on osteoporotic vertebral compression fracture / 中国组织工程研究

BACKGROUND: Percutaneous vertebral body stenting system (VBS) can alleviate patient's pain, recover the height of vertebral body, and correct local kyphosis, but there is no definite clinical study to show that It has obvious advantages over percutaneous kyphoplasty (PKP). OBJECTIVE: To compare the short-term effect of VBS versus PKP in the treatment of osteoporotic vertebral compression fracture. METHODS: Forty patients with osteoporotic vertebral compression fracture who received VBS or PKP between January 2017 and December 2018 In the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were included in this study. They were divided into a VBS group (n=15) and a PKP group (n=25) according to surgery method. According to whether fluoroscopic operation was performed in retroextension position, two subgroups were designated: VBS retroextension group (n=7) and PKP retroextension group (n=14). RESULTS AND CONCLUSION: Compared with the PKP group, the amount of bone cement injected Into the vertebra was greater in the VBS group (P 0.05). Compared with preoperative situations, Visual Analogue Scale score was significantly decreased after surgery In both VBS and PKP groups, and further decreased at the last follow-up (P 0.05). These results suggest that VBS and PKP are effective in the treatment of osteoporotic vertebral compression fractures. VBS can better correct compression kyphosis deformity when more bone cement Is injected. The difference of therapeutic efficacy between two surgical approaches can be reduced with proper surgical position, keeping the surgical segment In the retroextension position.

Three-dimensional printing technology and bone tissue engineering research: Literature metrology and visual analysis of research hotspots / 中国组织工程研究

BACKGROUND: With the continuous development of three-dimensional (3D) printing technology and bone tissue engineering, more and more studies have applied 3D printing technology to bone tissue engineering, but the main research status, hot spots and development trend are not clear enough. OBJECTIVE: To explore the current research status, hotspots and development trends of this field through the literature metrology and visual analysis of research hotspots of 3D printing and bone tissue engineering. METHODS: The CNKI database was searched under the theme of “3D printing and bone tissue engineering research”. Based on the quantitative visual analysis method of CNKI literature, the author made a statistical analysis on the trend of the number of publications, publishing institutions and journals of the application of 3D printing technology in bone tissue engineering. VOSviewer software was used to analyze the author collaboration and keyword co-occurrence network of the literature, and the hot research topic was interpreted based on the literature. RESULTS AND CONCLUSION: (1) A total of 469 effective articles related to 3D printing and bone tissue engineering were retrieved. Since 2014, the research on 3D printing and bone tissue engineering has shown a steady growth trend. Chinese Journal of Tissue Engineering Research and Jilin University are the most published journal and institution in this field, respectively. The authors of the literature form five major groups, but there is very little cooperation between the groups. (2) Keywords co-occurrence network shows that the contents revealed by keywords commonly clustering into four research topics (bone tissue engineering scaffold material, 3D printing technology and its application in orthopedics, 3D printing and joint replacement, and others) and the top 10 keywords (3D printing technology, computer aided technology, bone tissue engineering, tissue engineering, fracture, bone defect, hydroxyapatite, three-dimensional, replacement, titanium alloy) really reflect the present situation and the hotspots of current 3D printing and the bone tissue engineering research, which can provide a reference for researchers in this field when choosing a research direction.

Effects and mechanisms of enamel matrix derivatives on osteogenic differentiation of bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Bone marrow mesenchymal stem cells have good potential for directional differentiation, but the effect and mechanism of enamel matrix derivatives on osteogenic differentiation are still unclear. OBJECTIVE: To summarize the latest research progress on osteogenic induction of bone marrow mesenchymal stem cells by enamel matrix derivatives. METHODS: Related literature from 2000 to 2020 was searched in CNKI, Wanfang Data, VIP Database, PubMed databases. The key words are “Emdogain® or enamel matrix derivatives, bone marrow mesenchymal stem cells”. The languages of the literature were set to Chinese and English. When retrieving some classic articles, the publication date could be extended appropriately. Finally, 62 English articles and 5 Chinese articles meeting the inclusion criteria were selected. RESULTS AND CONCLUSION: There are different reports on the osteogenic effect of enamel matrix derivatives on bone marrow mesenchymal stem cells. Enamel matrix derivatives may enhance the osteogenic induction ability of bone marrow mesenchymal stem cells, and may enhance the osteogenic effect by affecting cells or cell membranes, but the relevant mechanism is unclear.

Characteristics and application of bioabsorbable materials in orthopedics / 中国组织工程研究

BACKGROUND: Bioabsorbable materials have shown obvious advantages in clinical application for more than ten years, and have been widely used in many biomedical fields. OBJECTIVE: To review characteristics of bioabsorbable materials and their application in orthopedics. METHODS: The articles published in Wanfang, CNKI, VIP, and PubMed databases were searched by computer. The key words were “bioabsorbable materials, bioabsorbable metal materials, bioabsorbable inorganic materials, polymer materials, biocomposites” in Chinese, and “bioabsorbable/bioabsorbable material, metal material, polymer material, biocomposites” in English. RESULTS AND CONCLUSION: Absorbable metal materials have good mechanical properties. The corrosion mechanism of polymer materials is clear, which can predict the corrosion behavior and corrosion rate in vivo and in vitro, but its load-bearing performance is not as good as that of absorbable metal materials. After certain treatment, bioceramics have good biocompatibility, bone conductivity and osseointegration, but they are brittle and difficult to be formed. Biocomposites have the properties of component materials, and can also obtain new properties that single component materials do not have, so it has a wide application prospect.

Role of mesenchymal stem cells migration in bone injury repair / 口腔疾病防治

@#Mesenchymal stem cells (MSCs) are capable of self-replication and multi-directional differentiation, which are very important for the development and reconstruction of mesenchymal tissue. Bone tissue damage repair involves the participation of various cells and molecules. The recovery of bone mass requires sufficiently many MSCs to migrate to the damaged site to perform the reconstruction function. The local inflammatory response at the injury site can recruit MSCs and promote new bone formation. Simultaneously, niche changes during the migration of MSCs will affect their biological performance and initiate the phase of directed differentiation. This article explores the relevant mechanisms that mediate the migration of MSCs in the process of bone injury repair, including the regulation of immune cells and chemotactic signaling molecules in the inflammatory response in the bone repair stage through signaling pathways such as BMP/Smads. Then, it summarizes the mechanism by which the high matrix stiffness upregulates the expression of the integrin and focal adhesions to promote the MSCs migration and osteogenic differentiation. Simultaneously, the migration ability of MSCs can be regulated through drugs or genetic modification to promote the bone injury repair. The improvement of MSCs migration ability can shorten the time of bone tissue damage repair and improve the bone quality. This article reviews the role of the MSCs migration ability in bone tissue injury repair to provide a reference for the application of MSCs with high migration ability in the fields of stem cell therapy for bone related diseases and bone tissue engineering.

Research progress on the reconstruction of mandibular defects in adolescents / 口腔疾病防治

@#Mandibular defects in adolescents are mostly caused by surgical resection of benign and malignant tumors, trauma and jaw inflammation. The reconstruction of mandibular defects in adolescents is challenging. In addition to solving the problem of jaw reconstruction in adults, some clinical factors, including the influence of surgery on the growth of donor and recipient areas, the long-term effects of reconstruction, and the outcome of bone grafts, must also be considered. At present, the main reconstructive methods include autogenous bone grafts and distraction osteogenesis. Autogenous bone grafts are still the gold standard due to their long-term effects. Favorable growth potential after repair was shown in adolescent cases of mandibular reconstruction with fibula flap. Normal occlusion was restored, and a long-term stable effect was achieved in cases of condylar reconstruction with costal cartilage. The safety and clinical effects of distraction osteogenesis have been confirmed, but the long-term effects of large-scale mandibular defects are still uncertain. In addition, other tissue engineering techniques also have good application prospects for the repair and reconstruction of adolescent mandible defects, but more in-depth basic research and more extensive clinical trials should be performed to verify the efficacy.

Effects of hypoxia inducible factor-1α on osteogenic differentiation and angiogenesis related factors of bone marrow mesenchymal stem cells / 口腔疾病防治

Objective@#To investigate the level of hypoxia inducible factor-1α (HIF-1α) on osteoblasts and angiogenesis-associated cytokines in bone marrow mesenchymal stem cells (BMSCs) from SD rats.@*Methods@#BMSCs were isolated and cultured and identified by flow cytometry. Plasmid vectors containing upregulated and downregulated HIF-1α gene and a control vector were constructed. The plasmids were transfected into BMSCs by Lipofectamine®LTX transfection reagent, and the cells were divided into an overexpression experimental group, an overexpression control group, a low expression experimental group and a low expression control group. All components were stained with a lizarin red 3 d and 7 d after osteogenesis induction. The mRNA expression levels of the target gene HIF-1α, osteogenic differentiation-specific markers, including Runt-related transcription factor 2 (Runx2) and angiogenic markers, including platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β (TGF-β), were detected by RT-PCR. Western blot was used to detect the protein expression of the target proteins HIF-1α, Runx2, and PDGF-BB.@*Results@# The CD29- and CD45-positivity rates of BMSC surface markers identified by flow cytometry were 98.2% and 4.2%, respectively. RT-PCR results showed that the mRNA expression of HIF-1α, Runx2, TGF-β and PDGF-BB was observably increased (P < 0.001). The mRNA expression levels of HIF-1α, Runx2, TGF-β and PDGF-BB in BMSCs from the low expression experimental group were significantly reduced (P < 0.001). Western blot results showed that the expression levels of HIF-1α, Runx2 and PDGF-BB in BMSCs from the overexpression experimental group were all increased (P < 0.001). The expression levels of HIF-1α, Runx2 and PDGF-BB in BMSCs from the low expression experimental group were reduced (P < 0.001). Alizarin red staining results showed that the area of calcium nodules in the low expression experimental group was smaller than that in low expression control group, the area of red calcium nodules in the over expression experimental group was larger than that in over expression control group, and with the increase of osteogenic induction time, the calcification area of each group also increased.@*Conclusion@# Upregulation and downregulation of HIF-1α can regulate the osteogenic differentiation and the expression of angiogenesis related factors of BMSCs.

Effect of mechanical stimulation on the differentiation of stem cells in periodontal bone tissue engineering / 口腔疾病防治

@#Currently, cell transplantation in combination with scaffold materials are one of the main strategies in periodontal bone tissue engineering. In periodontal bone tissues, the stiffness and spatial structure of tissues such as alveolar bone and cementum differ, and the difference in mechanical properties of scaffolds also has disparate effects on the proliferation and differentiation of stem cells. Accumulating evidence shows that mechanical stimulating factors such as matrix stiffness and scaffold topography modulate biological behaviors of various seeding cells, including adipose-derived stem cells and periodontal ligament stem cells. A hard matrix can promote cytoskeletal stretching of stem cells, leading to nuclear translocation of Yes-associated protein (YAP) and promoting osteogenic differentiation by upregulating alkaline phosphatase (ALP) and osteocalcin (OCN) via the Wnt/β-catenin pathway. The topologic structure of scaffolds can affect cell adhesion and cytoskeletal remodeling, increase the hardness of cells and promote the osteogenic differentiation of stem cells. In this paper, the effects of mechanical stimulation on the differentiation of stem cells in periodontal bone tissue engineering are reviewed.

Application and research status of bioactive glass in bone repair / 中国修复重建外科杂志

Objective: To summarize the clinical application and research status of bioactive glass (BAG) in bone repair. Methods: The recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized. Results: BAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made. Conclusion: BAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.

Application status of hypoxia mimetic agents in bone tissue engineering / 中国修复重建外科杂志

Objective: To summarize the application status of hypoxia mimetic agents in bone tissue engineering. Methods: The related literature about the hypoxia mimetic agents in bone tissue engineering was reviewed and analyzed. And the application status and progress of hypoxia mimetic agents in bone tissue engineering were retrospectively analyzed. Results: Hypoxia mimetic agents have the same effect as hypoxia in up-regulating the level of hypoxia inducible factor 1α (HIF-1α). The combination of hypoxia mimetic agents and scaffolds can up-regulate the level of HIF-1α in bone tissue engineering, thus promoting early vascularization and bone regeneration of the bone defect area, which provides a new idea for using bone tissue engineering to repair bone defect. At present, the commonly used hypoxia mimetic agents include iron chelating agents, oxoglutarate competitive analogues, proline hydroxylase inhibitors, etc. Conclusion: Hypoxia mimetic agents have a wide application prospect in bone tissue engineering, but they have been used in bone tissue engineering for a short time, more attention should be paid to their possible side effects. In the future research, the hypoxia mimetic agents should be developed in the direction of higher targeting specificity and safety, and the exact mechanism of hypoxia mimetic agents in promoting bone regeneration should be further explored.

Pressing local acupoints plus adjustion of the knee joint in a sitting position for treating knee osteoarthritis: A randomized controlled trial / 中国组织工程研究

BACKGROUND: Tuina for knee osteoarthritis has obvious curative effect, and has been widely used in clinical practice due to its characteristics, including simple operation, popularization, and good comfort. OBJECTIVE: To observe the clinical effect of the combination of pressing points of local acupoint plus adjustion of the knee joint in a sitting position in the treatment of knee osteoarthritis under “emphasizing both bones and tendons” as the guiding ideology of Tuina. METHODS: Ninety-one patients with knee osteoarthritis were randomly divided into a treatment group (n=46) and a control group (n=45). The treatment group was given the pressing points of local acupoint plus adjustion of the knee joint in a sitting position, and the control group was treated with oral celecoxib for 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the pressure pain thresholds, the Visual Analogue Scale scores at rest and at movement, and Hospital Anxiety and Depression Scale score were analyzed before and after treatment. The total clinical efficacy and adverse reaction index score were observed. The study was approved by the Ethics Committee of Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine on June 5, 2017, approval number: 2017-k-11. All participants were informed of the trial protocol and process, and signed informed consent. This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, ChiCTR1900022928) on May 4, 2019. RESULTS AND CONCLUSION: After 4 weeks of treatment: (1) The scores of WOMAC in both groups were improved compared with the baseline, and those in the treatment group decreased more significantly (P 0.05). Overall, the above results indicate that with “emphasizing both bones and tendons” as the guiding ideology of Tuina, the clinical effect of the pressing points of local acupoint and adjustion of the knee joint in a sitting position in the treatment of knee osteoarthritis is better than that of oral celecoxib.

Application and research of non-coding RNA in bone tissue engineering with cells and scaffold / 中国组织工程研究

BACKGROUND: Since non-coding RNAs maintain bone homeostasis through various pathways, applications of non-coding RNAs as bioactive molecules in bone tissue engineering for bone defect repair has become an increasing area of interest. OBJECTIVE: To introduce non-coding RNAs as bioactive molecules in bone tissue engineering. METHODS: A computer-based online search of Web of Science, PubMed, SpringerLink databases was performed by the first author between December 2018 and March 2019 using the search terms “bone tissue engineering, ncRNA (miRNA, siRNA or lncRNA), scaffold, drug delivery system” to retrieve papers published during 2004-2019. A total of 1754 papers were preliminarily retrieved, and 95 of them were eligible for final analysis. RESULTS AND CONCLUSION: Because non-coding RNAs play a key role in osteogenic differentiation, they can be used as important bioactive factors for bone tissue engineering. At present, bone tissue engineering repair methods based on non-coding RNA bioactive factors have become a research hotspot in bone defect repair. There are two major application strategies: (1) The non-coding RNA transcription within the seed cells is purposefully altered and combines with the bone tissue-engineered scaffold to promote bone defect repair. (2) a specifically designed bone engineered scaffold can controllably and purposefully alter the expression of non-coding RNA in the seed cells, which promotes bone defect repair. In addition, the function of more and more non-coding RNAs has been identified in the process of bone regeneration. This shows good application prospects of non-coding RNAs.

In vitro biocompatibility of 3D printed polycaprolactone/nano-hydroxyapatite composite scaffold with bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Polycaprolactone/nano-hydroxyapatite composite is a new composite scaffold material prepared based on common bone tissue engineering materials using 3D printing technology. At present, little is reported on the in vitro biocompatibility of the composite material. OBJECTIVE: To investigate the cytocompatibility of 3D printed polycaprolactone/nano-hydroxyapatite composite scaffolds. METHODS: Polycaprolactone and polycaprolactone/nano-hydroxyapatite composite scaffolds were prepared by 3D printing technology to characterize the microstructure, porosity and mechanical properties of the two materials. Rat bone marrow mesenchymal stem cells were inoculated on the surface of the 3D-printed polycaprolactone and polycaprolactone/nano-hydroxyapatite composite scaffolds. Cell proliferation rate was detected by CCK-8 method. Cell growth on the scaffolds was observed by scanning electron microscopy and Live/Dead cell staining. RESULTS AND CONCLUSION: Two kinds of scaffolds had a three-dimensional network and interconnected structure. The fibers were arranged in a regular order and interlaced. There was no gap on the fiber surface, and the fiber spacing and diameter were relatively uniform. There was no significant difference in the porosity between two kinds of scaffolds (P > 0. 05). The elastic modulus of the composite scaffold was higher than that of the simple polycaprolactone scaffold (P < 0. 05). There was no significant difference in cell proliferation between two kinds of scaffolds after 1 day of culture. After 4 and 7 days of culture, cell proliferation on the composite scaffold was significantly faster than that on the simple polycaprolactone scaffold (P < 0. 05). Live/Dead cell staining showed that both polycaprolactone and polycaprolactone/nano-hydroxyapatite composite scaffolds had good cytocompatibility and high cell viability. A larger number of cells adhered to the polycaprolactone/nano-hydroxyapatite composite scaffolds. Scanning electron microscopy showed that cells grew well on two kinds of scaffolds and distributed on the surface and micropores of the scaffold. The secreted extracellular matrix appeared in filaments and surrounded the cells. These findings suggest that the polycaprolactone/nano-hydroxyapatite composite material prepared by 3D printing technology has abundant pores, exhibit good mechanical properties, and have good cytocompatibility and can be used as a scaffold material for tissue engineering.

Research progress in osteogenic differentiation of adipose-derived stem cells induced by bioscaffold materials / 中国组织工程研究

BACKGROUND: Adipose-derived stem cells are easy to access and have strong proliferative capacity, which are considered as ideal seed cells for bone defect repair. The bone tissue engineering research progress reveals that bioscaffold material modification can directly regulate the osteogenic differentiation of stem cells. OBJECTIVE: To review various biological scaffold materials that can regulate the osteogenic differentiation of adipose-derived stem cells. METHODS: The first author searched the articles in CNKI, WanFang, VIP, PubMed, Embase and Web of Science databases published from January 2016 to May 2019. The search terms were “adipose derived stem cells, scaffold, osteogenic, metal, Ti” in Chinese and English, respectively. Finally 62 eligible articles were selected. RESULTS AND CONCLUSION: Scaffold materials for bone tissue engineering are classified into inorganic materials (hydroxyapatite, tricalcium phosphate, bioglass, titanium, and magnesium), natural polymer materials (collagen, silk fibroin, and chitosan) and synthetic polymer materials (polycaprolactone, polylactic acid, polyglycolic acid and poly(lactic-co-glycolic acid)). The studies on materials that interact with cells to guide their biological response and bone differentiation are increasing. But how to create a safe, rational, and close to the micro-environment of cell growth in vivo is a challenge. Modification of bioscaffold materials can directly regulate osteogenic differentiation of stem cells. Moreover, vascularization and post-implantation infections are issues of concern.

Application of bone tissue engineering materials in the treatment of bone defect diseases in vivo / 中国组织工程研究

BACKGROUND: The application of bone tissue engineering materials to treat bone defect diseases is a hot topic of current research. Material selection and design of in vivo experiments are the focus of research. OBJECTIVE: To summarize the research progress of bone tissue engineering materials for repairing bone defects in vivo in the past 10 years. METHODS: A search was conducted in CNKI, Wanfang, and PubMed with the key words of “bone tissue engineering, bone defect and in vivo experiment” for articles published from January 2010 to December 2019. Totally 264 articles were retrieved, and 74 eligible articles were finally summarized after screening. RESULTS AND CONCLUSION: Bone tissue engineering is a new method for treating bone defect diseases, but there are many types of bone tissue engineering materials in practical application. The single material inevitably has limitations in the application of materials. Composite materials can improve material properties and bone repair capacity. Simultaneously, the in vivo experiment is a powerful test to verify the practical application of the material, and it can detect the shortcomings that were not found in the in vitro experiments, and provide data support for the practical application of bone tissue engineering materials.