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【Objective】 To construct a 3D printed PLLA/β-tricalcium (PLLA/β-TCP) bone tissue engineering scaffold surface porous structure through simple treatment with NaOH solution, increase the roughness and hydrophilicity of the scaffold, and promote cell adhesion on the scaffold surface. 【Methods】 The PLLA/β-TCP mesh scaffold was prepared by 3D printing melt deposition molding technology, and the scaffold was roughed by NaOH etching. The effects of NaOH concentration and time on the scaffold were observed according to the microstructure, energy spectrum, contact angle, mechanics, and cell adhesion of the scaffold. 【Results】 The PLLA/β-TCP composite scaffold constructed by melt deposition technology had a pre-set porous structure, and the pores were interconnected. After NaOH etching, a porous structure with both macroscopic and microscopic pores was formed. The increase in any of the NaOH concentration and time parameters would lead to the increase of pore diameter and surface roughness. When the NaOH treatment parameter was 0.1 mol/L (9 h), it could significantly reduce the water contact angle on the surface of the scaffold, and had no significant effect on the compressive strength of the scaffold. In vitro cell testing showed that the surface porous composite scaffold etched with NaOH had more advantages in the adhesion and proliferation of BMSCs. 【Conclusion】 Using NaOH to process 3D printing of PLLA/β-TCP bone tissue engineering scaffolds can effectively improve the surface morphology of the scaffold, and optimize its hydrophilicity and cell adhesion.
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【Objective】 To solve the problem of insufficient hydrophilicity on the surface of polycaprolactone (PCL)/β-TCP bone tissue engineering scaffolds, NaOH etching method was used to improve the surface microstructure of 3D printed PCL/β-TCP scaffolds, further affecting their hydrophilicity and cell response. 【Methods】 PCL/β-TCP mesh scaffolds were prepared using 3D printing melt deposition molding technology, and the surface roughness of the scaffolds was modified by NaOH etching. The effects of two reaction parameters, NaOH concentration and time, on the microstructure, spectral elements, contact angle, compressive strength, and cell adhesion of the scaffolds before and after modification were observed. 【Results】 After NaOH etching, the surface microporous structure of the mesh scaffold was successfully prepared. With the increase of either NaOH concentration or time, the surface micropores of the scaffold increased while the contact angle of the material surface decreased. However, the compression strength of the etched scaffold treated with NaOH for 1 mol/L (24 h) or 10 mol/L (6 h) was not statistically significant compared to the untreated group (P>0.05). The number of cells on the etched scaffold increased, with a larger spreading area of individual cells, making it more advantageous in the adhesion and proliferation of BMSCs. 【Conclusion】 The use of NaOH etching to improve the hydrophilicity of 3D printed PCL/β-TCP bone tissue engineering scaffolds is a low-cost and effective strategy which can effectively improve the wettability and cell adhesion of the scaffolds.
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@#Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.
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Bioactive glass(BG)has been used as a candidate for bone and soft tissue repair materials because of its compatibility,bioactivity and ability to form a crystalline hydroxyapatite layer.This paper introduces the mechanism of BG ion release,discusses the application of borosilicate bioactive glass(BBG)in bone and soft tissue repair,and provides an overview of the potential and clinical translational challenges faced by BBG in bone cement,scaffold,hydrogel,and fiber research applications.
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BACKGROUND:The repair of maxillofacial bone tissue defects is a hot and difficult point in current research and the selection of seed cells is the key.Jaw bone marrow mesenchymal stem cells are adult mesenchymal stem cells that exist in the jaw bone.They have advantages in the application of maxillofacial tissue regeneration. OBJECTIVE:To summarize the biological characteristics,osteogenic differentiation advantages of jaw bone marrow mesenchymal stem cells,and the effects of drugs,in vivo environment,and microRNAs on the osteogenic differentiation of jaw bone marrow mesenchymal stem cells. METHODS:Computers were used to perform literature retrieval in PubMed and CNKI.Chinese and English search terms were"oral,bone tissue engineering,stem cells".405 articles were retrieved and downloaded.The articles were screened according to the inclusion and exclusion criteria and 70 articles were finally included for literature review. RESULTS AND CONCLUSION:Jaw bone marrow mesenchymal stem cells were excellent seed cells for oral bone tissue engineering,and had good proliferation and osteogenic differentiation potential.Drugs,in vivo environment and microRNAs could regulate the osteogenic differentiation of jaw bone marrow mesenchymal stem cells.However,the research on jaw bone marrow mesenchymal stem cells was still in the initial stage,so more research with strong demonstration is needed to confirm that jaw bone marrow mesenchymal stem cells have more advantages in the application of maxillofacial bone tissue regeneration.
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BACKGROUND:Metal ions play an important role in the human body.With the progress of material synthesis and processing technology,a variety of metal ions that can be used in bone tissue engineering have been developed,such as magnesium(Mg2+),zinc(Zn2+),manganese(Mn2+),strontium(Sr2+),and copper(Cu2+). OBJECTIVE:To summarize the research progress and development direction of metal ions in bone tissue engineering. METHODS:The literature collected by CNKI,PubMed and WanFang databases from 2014 to 2022 was retrieved.The Chinese and English key words were"metal ions,bone tissue engineering,osteogenic activity,magnesium ions,zinc ions,manganese ions,strontium ions,copper ions,calcium ions,lithium ions,cobalt ions". RESULTS AND CONCLUSION:Different metal ions will be released to varying degrees after the materials are implanted into the body,which can change the tissue microenvironment,thus improving the ability of materials to form blood vessels and bones.Compared with growth factors,metal ions are easier to control the release rate,have lower cost,and can also improve the mechanical properties of implant materials.The application of metal ions in bone tissue engineering is full of prospects.Although some metal ions can already be used to treat bone defects,the mechanism of action of many metal ions in the human body is not completely clear,and the application effect is a lack of clinical experiment verification.Further exploration is needed before clinical application.
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BACKGROUND:Magnetically responsive hydrogels have great advantages in bone tissue engineering,which is more conducive to the minimally invasive and efficient promotion of osteogenesis. OBJECTIVE:To review the application advances of magnetically responsive hydrogels in bone tissue engineering. METHODS:PubMed,Web of Science,WanFang and CNKI databases were used to search relevant literature.The English search terms were"Magnetic Hydrogels,Magnetic Nanoparticles,Superparamagnetic Nanoparticles,Fe3O4,SPIONs,Magnetic Fields,Bone Regeneration,Bone Repair,Bone Tissue Engineering".The Chinese search terms were"Magnetic Hydrogel,Magnetic Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Magnetic Field,Iron Oxide Nanoparticles,Bone Regeneration,Bone Reconstruction,Bone Repair,Bone Tissue Engineering".After preliminary screening of all articles according to the inclusion and exclusion criteria,60 articles were finally retained for review. RESULTS AND CONCLUSION:(1)In recent years,due to the emergence of magnetic nanoparticles,more and more magnetic responsive scaffold materials have been developed.Among them,magnetic responsive hydrogels containing iron oxide nanoparticles and superparamagnetic iron oxide nanoparticles have outstanding mechanical properties and good biocompatibility.It can quickly respond to the external magnetic field and provide the magnetic-mechanical signals needed for seed cells to form bone.(2)Magnetic-responsive hydrogel can be used as a carrier to accurately regulate the release time of growth factors.(3)Under the three-dimensional microenvironment culture platform based on magnetically responsive hydrogel,the magnetic force at the interface between the magnetic response hydrogel and cells can activate cell surface sensitive receptors,enhance cell activity,and promote the integration of new bone and host bone.(4)The injectable magnetically responsive hydrogel can be used in the field of magnetic hyperthermia and biological imaging of bone tumors.(5)At present,magnetically responsive hydrogels are expected to mimic the anisotropic layered structure observed in natural bone tissue.However,most of the studies on magnetically responsive hydrogels focus on in vitro studies,and the mechanism of interaction between magnetically responsive hydrogels and the local microenvironment in vivo is still insufficient.(6)Therefore,based on the successful application of magnetic nanoparticles in magnetic resonance imaging,it is expected to optimize the properties of magnetic nanoparticles in the future to construct magnetic responsive hydrogels with suitable degradation properties,mechanical properties,and vascular functionalization,which can monitor changes in vivo in real time.
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BACKGROUND:Hydrogel microparticles,due to their porous and injectable properties,have demonstrated unique advantages in biomedical fields,such as the delivery of cells and bioactive factors/drugs,the construction of tissue repair scaffolds.They have broad application prospects. OBJECTIVE:To review the latest research progress and discuss the key problems and challenges in the research of bone tissue engineering based on hydrogel microparticles. METHODS:The relevant articles in PubMed and CNKI were searched by computer.The English key words were"hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering"while the Chinese key words were"hydrogels,microparticles,microspheres,bone tissue engineering,bone defect,bone repair,bone regeneration".The retrieval period was from 2002 to 2022,and 127 articles were finally included for review. RESULTS AND CONCLUSION:(1)At present,various hydrogel microparticles have been developed for use in bone tissue engineering strategies,for example,hydrogel microparticles carrying cells or bioactive factors/drugs,hydrogel microparticles as biological scaffolds,stimulus-responsive hydrogel microparticles,biomineralized hydrogel microparticles,hydrogel microparticles combined with other biological materials.(2)Bone tissue engineering repair strategies based on hydrogel microparticles mainly regulate bone repair by promoting stem cell recruitment and osteogenic differentiation,regulating the local inflammatory microenvironment and promoting angiogenesis at the site of injury.However,the present studies did not deeply explore the effect of bone tissue engineering based on hydrogel microparticles on the recruitment and differentiation of endogenous stem cells and the regulation of the inflammatory microenvironment by the physical and chemical properties of hydrogel microparticles.The long-term in vivo adverse reactions of hydrogel microparticles have not been explored yet,and it is difficult to mass-produce them,thus future research needs to strengthen the mechanism exploration and technical route,so as to provide a reasonable reference for the development of hydrogel microparticles that can be used for clinical transformation.
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BACKGROUND:At present,nanocomposite gelatin methacryloyl hydrogels have been extensively studied in bone tissue engineering. OBJECTIVE:To review the latest research progress of nanocomposite gelatin methacryloyl hydrogels,and introduce the application of nanocomposite gelatin methacryloyl hydrogels in different bone defect environments. METHODS:The computer retrieval was conducted for relevant literature published in CNKI,WanFang,PubMed,and Web of Science databases from 2016 to 2023.The Chinese and English search terms were"gelatin,methacryl*,nano*,bone,bone tissue engineering,bone regeneration,osteogenesis". RESULTS AND CONCLUSION:(1)Up to now,inorganic nanomaterials,organic nanomaterials and organic-inorganic hybrid nanomaterials are the main nanomaterials used as fillers for gelatin methacryloyl.(2)Inorganic nanomaterials enhance the mechanical strength of gelatin methacryloyl,improve its thixotropic properties and degradation rate,and realize the antibacterial,osteogenic,immunoregulatory,angiogenic and other functions of gelatin methacryloyl hydrogel through its surface charge regulation,drug/factor loading,metal ion self-degradation release,etc.(3)Organic nanomaterial and organic-inorganic hybrid nanomaterial composite gelatin methacryloyl hydrogel are two emerging materials.At present,there are relatively few studies,but from the published research,compared with inorganic nanomaterial gelatin methacryloyl hydrogel,organic nanomaterial gelatin methacryloyl hydrogel has better biocompatibility and drug-loading performance.The interaction between nano phase and organic polymer phase is stronger,and the dispersion of nano particles is better.(4)Organic-inorganic hybrid nanomaterial composite gelatin methacryloyl combines the advantages of the previous two,and has better controllability of metal ion release,which proves great research potential.(5)Nanomaterials can enhance the antibacterial,immune regulation,osteogenesis and other biological properties of gelatin methacryloyl,so as to promote bone regeneration in the complex bone defect microenvironment,such as infected bone defect,diabetes,osteosarcoma resection and so on.However,the relevant research of nanocomposite gelatin methacryloyl hydrogel in bone repair is still limited to animal experiments.Further safety testing and clinical studies are still needed.
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BACKGROUND:Owing to excellent angiogenesis activity and their participation in the physiological processes such as angiogenesis in osteogenesis,the researches and applications of a variety of metal ions are getting deeper in the field of bone tissue engineering. OBJECTIVE:To systematically explain the mechanism of angiogenesis of different metal ions such as copper ion(Cu2+),magnesium ion(Mg2+),strontium ion(Sr2+),zinc ion(Zn2+),cobalt ion(Co2+)and their current research situation as well as application in the treatment of diseases in the field of bone tissue engineering. METHODS:The two authors used PubMed and CNKI to search the literature published between 2017 and 2022 with the search terms"copper ion,magnesium ion,strontium ion,zinc ion,cobalt ion,bone,angiogenesis"in Chinese and"copper,cuprum,Cu,magnesium,Mg,strontium,Sr,zinc,Zn,cobalt,Co,metal ion,angiogenesis,bone"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant articles were excluded.Finally,114 articles were included for review. RESULTS AND CONCLUSION:(1)Metal ions can regulate angiogenesis by acting on vascular endothelial growth factors,hypoxia-inducible factors,angiogenesis-related genes,endothelial cells and conducting immune regulation of macrophages.(2)Metal ions such as copper,magnesium,strontium,zinc and cobalt are often used to improve the performance of tissue engineering scaffolds due to their significant angiogenic effect.Among them,hydrogels,bioceramics and synthetic polymer materials are widely used at present,and magnesium and its alloys also have advantages due to their excellent bearing capacity.However,these materials all have some defects.Currently,there is no ideal bone replacement material.(3)Various metal ions show different application potentials in bone replacement materials:Copper has antibacterial,angiogenic and osteogenic properties,and is mainly used for bone defects caused by infection and tumors.Magnesium and zinc have strong biodegradability,so the degradation rate should be controlled.Magnesium is corrosive and is mainly used as an alloy.The angiogenesis mechanism of zinc is less involved.Magnesium and strontium are effective in treating osteoporotic bone defects.(4)The above five metal ions(copper,magnesium,strontium,zinc and cobalt)have a significant role in promoting angiogenesis and then promote osteogenesis through angiogenesis.Some ions,such as copper ions,have a bactericidal effect.These ions can be used as a new strategy for the treatment of bone defects caused by tumors,osteoporosis,infection and trauma,but the current clinical trials and application studies of products are relatively insufficient.
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BACKGROUND:In response to the limitations of traditional repair methods for bone defects,stem cells are widely used in the research of regenerative medicine.Chemical factors are the current research hotspots,but recent studies confirm that the application of physical factors to regulate stem cell differentiation at home and abroad has been intensifying,and physical factors combined with biological scaffolds in bone tissue engineering provide a new idea and method for solving the difficult problem of bone defect repair,with good development prospects. OBJECTIVE:To summarize the molecular mechanisms of physical factors such as electromagnetic fields and ultrasound on osteogenic differentiation of stem cells as well as the regulation of signaling pathways and the feasibility of their application in bone tissue engineering. METHODS:A computerized search of the CNKI and PubMed for the last 20 years was conducted.In the title and abstract,we used"stem cell,bone defect,osteogenic differentiation,electromagnetic fields,ultrasound,shock wave,low-level laser therapy,mechanical force,bone tissue engineering"in Chinese and"stem cell,osteoporosis,osteogenic differentiation,electromagnetic fields,ultrasound,bone tissue engineering"in English as search terms.A total of 94 relevant articles were included for review. RESULTS AND CONCLUSION:(1)As a non-invasive,non-contact adjuvant therapy,physical factors have a significant impact on bone tissue engineering,and have a positive effect on regulating osteogenic differentiation of stem cells,promoting cell proliferation and viability in bone engineering scaffolds.(2)In addition to activating signaling pathways and osteogenic gene transcription,physical factors can also improve vascularization,increase the volume,area and thickness of bone formed in the stent,promote osseointegration,and improve the success rate of bone scaffolds in regenerating healthy bone tissue.(3)However,the use of physical factors for bone tissue engineering uses different experimental conditions,such as scaffold type,cell type,and intervention conditions,and cannot be directly compared to determine the best parameter settings.There is also a lack of consistency in the effectiveness of these different interventions in promoting fracture healing in clinical use.Therefore,it is necessary to further determine the optimal parameters of physical factors for bone tissue engineering in the future.(4)In general,as an ideal adjuvant therapy,physical factors have great potential in combining with various biomaterials and applying them in bone tissue engineering.
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BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.
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BACKGROUND:Hydroxyapatite is the main inorganic component of bone tissue.The polymer has the structure and function of a biomimetic extracellular matrix.The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE:To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS:The articles collected in PubMed,Web of Science,CNKI and WanFang databases were searched from January 2010 to April 2023.The Chinese and English search terms were"hydroxyapatite,polymer,composites,degradability,bone defect,bone repair".Finally,75 articles were included for review. RESULTS AND CONCLUSION:Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers(collagen,chitosan,alginate,serine protein,cellulose,hyaluronic acid,and polyhydroxybutyrate)and synthetic polymers[polylactic acid,polylactic acid-hydroxyacetic acid copolymer,poly(has-lactide),poly(amino acid)and poly(vinyl alcohol)].The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite.Hydroxyapatite composite with polymers can be made into porous scaffolds,hydrogels,and coatings for bone repair.Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function.Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins,repair materials with mechanical properties matching bone tissue,degradation processes synchronized with bone repair,and efficient osteogenesis and vascularization need to be further investigated.
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BACKGROUND:Adjustable piezoelectric effect can promote tissue regeneration and repair.Piezoelectric materials are widely used in weight-bearing tissue engineering. OBJECTIVE:To prepare a piezoelectric film material that can promote bone regeneration,and to explore its structural characterization,electrical output performance,biocompatibility,and effect of electrical output on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. METHODS:Using poly-3-hydroxybutyrateco/4-hydroxybutyrate(P34HB)as raw material,barium calcium stannate titanate powder(Ba0.94Ca0.06Sn0.08Ti0.92O3,BCST)was added according to mass ratios of 0%,5%,10%,15%,and 20%.Dichloromethane was added to solve P34HB,and the thickness of 150-200 μm BCST/P34HB piezoelectric film was prepared by vacuum drying method.After polarization in the oil bath,the surface morphology,crystal phase composition,piezoelectric coefficient and open circuit voltage were tested.The effect of BCST/P34HB electrical output at 110 Hz and 0.25 N force on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells was tested. RESULTS AND CONCLUSION:(1)Scanning electron microscopy,X-ray diffraction,water contact angle,piezoelectric coefficient and electrical output performance tests showed that when the mass ratio of BCST increased to 20%,the BCST/P34HB piezoelectric film had good piezoelectric properties(d33=5.9 pC/N)and electrical output performance(180 mV),which was closer to the suitable range of 500 mV for electrical stimulation.(2)Live and dead staining showed that on the first day of co-culture,15%group and 20%group showed less red fluorescence.On the 5th day of culture,the number of green fluorescence in each group was significantly higher than that on the first day,and the red fluorescence was not observed in the 10%,15%and 20%groups,and only a small amount of red fluorescence was observed in the 0%and 5%groups.(3)On the 1st,3rd and 5th days of co-culture with rabbit bone marrow mesenchymal stem cells,Almar blue staining exhibited that the number of cells in each group showed an increasing trend with the increase of time.On the 5th day of culture,the number of cells in the 20%group was significantly more than that in the 0%group(P<0.05).(4)On day 10 of osteogenic induction,alkaline phosphatase staining results showed that the positive rate of the 20%group was significantly higher than that of the 0%group(P=0.000 1).On day 21,alizarin red staining and quantitative analysis of calcium nodules showed a similar trend to alkaline phosphatase staining.Compared with the 0%group,the 15%group and 20%group showed significant differences(P<0.01,P<0.000 1).(5)The results showed that 20%BCST/P34HB films had good piezoelectric properties,electrical output properties,biocompatibility and the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells.
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BACKGROUND:Polyvinylidene fluoride(PVDF)with piezoelectric properties,good biocompatibility and nontoxicity make it a suitable candidate for periosteal repair. OBJECTIVE:To evaluate the cytotoxicity of PVDF bionic periosteum by electrospinning with zinc and magnesium ions in vitro. METHODS:Pure PVDF,zinc-doped PVDF,magnesium-doped PVDF and Zinc-magnesium ion PVDF piezoelectric bionic periosteum were prepared by electrospinning technology,respectively.They were named PVDF,PVDF-Zn,PVDF-Mg and PVDF-Zn-Mg,in which the mass fraction of zinc and magnesium ions were all 1%.Osteoblasts and vascular endothelial cells were co-cultured with four groups of bionic periosteum.Cell compatibility of bionic periosteum was determined by alkaline phosphatase staining,CD31 immunofluorescence staining,and scanning electron microscopy. RESULTS AND CONCLUSION:(1)Osteoblasts:Alkaline phosphatase staining after 7 days of culture showed that the PVDF-Zn group secreted more alkaline phosphatase than the other three groups.Under a scanning electron microscopy,after 1 day of culture,the cells had a certain spread on the surface of PVDF-Mg and PVDF-Zn-Mg bionic periosteum,and the pseudopod extended to all sides.On day 3,the cell edge of each group extended pseudopods to the material.By days 5 and 7,the cells were fully spread,well grown and firmly covered the surface of the fibers,and the cellular pseudopods extended around and into the interstitial space of the fibers.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed an increasing trend over time and the relative proliferation rate of cells at 1,3,5,and 7 days was≥75%,and the cytotoxicity was≤grade 1.(2)Vascular endothelial cells:CD31 immunofluorescence staining for 3 days showed that the cells adhered and spread well on the bionic periosteum of each group and connected with each other,and the number of cells in the PVDF-Zn-Mg group was more than that in the other three groups.Under scanning electron microscope,the cells began to adhere to the surface of each group of fibers after 1 and 3 days of culture.On day 5,the cells were well spread on the surface of the fibers and extended obvious pseudopods.On day 7,the cells on the PVDF-Mg and PVDF-Zn-Mg bionic periosteum grew in multiple layers and extended the pseudopod into the fibrous void.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed a downward trend over time,and the relative proliferation rate of cells at 1,3,5 and 7 days was≥125%,and the cytotoxicity was grade 0.(3)The results showed that Zn-Mg electrospun PVDF piezoelectric bionic periosteum had good cytocompatibility.
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BACKGROUND:Bone tissue defects are one of the most common diseases in orthopedics,and the current treatments for this disease are inadequate.The development of tissue engineering brings new hope for bone defect repair:by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site,it can effectively improve the microenvironment of bone tissue and promote osseointegration,which is the most promising research idea for large-size bone defect repair. OBJECTIVE:To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances,vascularization and neurotization on three aspects of bone microenvironment changes,and to provide new ideas and strategies for the treatment of large-size bone defects. METHODS:The search terms"bone tissue engineering,angiogenesis,neurotization,cytokines,bone morphogenetic protein,vascular endothelial growth factor,neuropeptides,bone microenvironment"in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1,2001 to December 31,2022 on CNKI,WanFang,Web of Science,Science Direct,and PubMed.Finally,109 articles were included for review. RESULTS AND CONCLUSION:(1)The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation,and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions,the local blood circulation network and the surrounding nerve tissue.(2)Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines,and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases.(3)Neovascular regeneration is key to initiating bone repair,as neovascularisation not only provides essential nutrients,osteoblasts and growth factors for bone repair,but is also a gateway for repair cells to enter the injury zone.(4)In addition to regulating the type,dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction.The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects.(5)Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing,bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways.(6)In the establishment of neuralized tissue-engineered bone,the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional.Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier.Neuropeptides secreted by glial cells act on the bone microenvironment,affecting bone healing,bone regeneration and the balance between osteogenesis and osteolysis.(7)There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis,such as the rapid diffusion and degradation of cytokines in the body and their loss of activity,the temporal and spatial distribution of angiogenesis-related growth factors,and the establishment of neurogenesis through the body's feedback regulatory mechanism,which need to be improved by subsequent studies.
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BACKGROUND:Bone is a remarkable natural material possessing piezoelectric properties.By harnessing the biomimetic piezoelectric effect,tissue engineering materials can be employed to effectively address bone tissue defects and facilitate their repair. OBJECTIVE:Using a solid-phase force chemistry technique,a piezoelectric scaffold with inherent osteogenic properties was meticulously fabricated.This unique scaffold was then assessed for its impact on osteoblast adhesion,proliferation,and osteogenic differentiation. METHODS:Polyvinylidene fluoride(PVDF)powders,along with commercially available NaCl(mass ratios are 60:40,50:50,40:60,and 30:70,respectively),were subjected to solid-phase shear milling technology,resulting in a homogenous mixture.Through a melting process,a substantial material was formed,and subsequent treatment with a pure water solution effectively eliminated the NaCl.Consequently,PVDF piezoelectric foam scaffolds with varying pore sizes were successfully prepared.These materials were categorized as PVDF-40,PVDF-50,PVDF-60,and PVDF-70,denoting the respective mass percentages of NaCl during preparation.The surface morphology,crystal phase composition,thermodynamic behavior,mechanical properties,and piezoelectric properties of each group were meticulously characterized.The four kinds of piezoelectric foam scaffolds were co-cultured with the MG63 osteoblast cell line to evaluate its biocompatibility and potential to promote bone differentiation. RESULTS AND CONCLUSION:(1)The scanning electron microscopy,four groups of scaffolds had multi-level pores.As the NaCl mass fraction in the mixed powder increased,the porosity of the scaffolds increased.X-ray energy dispersion spectrum,X-ray diffraction,Fourier transform infrared spectroscopy,and thermogravimetric analysis collectively revealed the scaffold predominantly comprised the α phase,which inherently lacked piezoelectric properties.However,the application of solid-phase force chemistry successfully stimulated the formation of the β phase,thereby enhancing the scaffold's piezoelectric properties.Notably,the PVDF-60 group exhibited the highest proportion of the β phase among all the tested groups.The results of cyclic compression testing and piezoelectric performance assessment demonstrated that the PVDF-60 group exhibited superior compressive strength and piezoelectric performance compared to the other groups.(2)The findings from scanning electron microscopy and laser confocal microscopy exhibited that MG63 cells adhered well to the surface of the four groups of scaffolds,with good morphology,extended more pseudopods,and secreted a large amount of extracellular matrix.CCK-8 assay revealed that the proliferative absorbance of PVDF-60 cells cultured for 4 days was higher than that of the other three groups(P<0.000 1).Alkaline phosphatase staining and alizarin red staining showed that the expression of alkaline phosphatase and the number of calcified nodules in the PVDF-60 group were higher than those in the other three groups(P<0.01,P<0.000 1).(3)The piezoelectric PVDF foam-based scaffolds demonstrated favorable cytocompatibility.Notably,the PVDF-60 group showed superior mechanical properties,piezoelectric performance,and bone-inducing capabilities.
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BACKGROUND:The repair of large-scale bone defects is still facing serious challenges.It is of great significance to develop personalized,low-cost,and osteogenic-inducing tissue engineering scaffolds for bone repair. OBJECTIVE:To explore the process of 3D printing bone tissue engineering scaffold containing pearl composite material by low-temperature condensation deposition method,and further test the physicochemical properties and in vitro biological functions of the composite scaffold. METHODS:Pearl powder was prepared by grinding and sieving.The pearl powder of different qualities was added into the poly-L-lactic acid ink,so that the mass ratio of pearl powder to poly-L-lactic acid was 0,0.1,0.2,0.3,and 0.5,respectively.The 3D-printed poly-L-lactic acid/pearl powder scaffolds were prepared using the low-temperature condensation deposition method.The microstructure,compressive properties,water contact angle,cytocompatibility,and in vitro bone differentiation ability of the printed poly-L-lactic acid/pearl powder composite scaffolds were detected. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the five groups of scaffolds all had micropores with a diameter of 2 μm or even smaller,irregular shapes and interconnectivity.(2)All the five groups had good compressive properties.The compressive strength of the pearl powder 0.5 group was higher than that of the other four groups(P<0.05).The water contact angle of the pearl powder 0.2 group and the pearl powder 0.5 group was smaller than that of the pearl powder 0 group(P<0.01,P<0.001).(3)Bone marrow mesenchymal stem cells were co-cultured with five groups of scaffolds for 1,3,and 5 days,respectively.The cell proliferation in pearl powder 0.1,0.2,0.3,and 0.5 groups cultured for 3 and 5 days was faster than that in pearl powder 0 group(P<0.05).After 1 day of culture,live-dead staining exhibited that the number of cells on the scaffold was small,but all of them were living cells.(4)Bone marrow mesenchymal stem cells were inoculated on the scaffold surface of the pearl powder 0 group and pearl powder 0.1 group respectively for osteogenic differentiation.The alkaline phosphatase activity induced for 4 and 6 days in the pearl powder 0.1 group was higher than that in the pearl powder 0 group(P<0.05).(5)The results showed that the poly-L-lactic acid/pearl powder composite scaffold had good compressive strength,hydrophilicity,cytocompatibility,and osteogenic properties.
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BACKGROUND:The study of the physical properties of scaffolds has always been a hot topic in the field of tissue engineering research.However,for vascular stimulating scaffolds,in addition to meeting the basic performance of the scaffold,other methods are also needed to promote the regeneration of blood vessels within the scaffold,in order to achieve the ultimate goal of repairing bone tissue. OBJECTIVE:A visualization analysis was carried out on the literature published in and outside China on scaffold stimulation for bone tissue engineering,to explore the research hotspots and research status in this field,and to provide a reference for subsequent studies. METHODS:Using the CNKI database and Web of Science core database as retrieval databases,the relevant literature on vascular scaffolds for bone tissue engineering was retrieved.The literature that did not conform to the research object was removed.The obtained data were imported into CiteSpace 6.1.R2 software.Visualization analysis was performed on authors,national institutions,and keywords in the research field. RESULTS AND CONCLUSION:(1)China,the United States,and Germany were the top three countries with the most articles on scaffold stimulation for bone tissue engineering.(2)The top 3 institutions in the CNKI database were Southern Medical University,Huazhong University of Science and Technology,and Donghua University.In the core database of Web of Science,Shanghai Jiao Tong University,Sichuan University and Chinese Academy of Sciences ranked the top 3 in terms of the number of institutional publications.(3)The top 3 keywords in the CNKI database were"tissue engineering,vascularization,angiogenesis".The top 3 keywords in the Web of Science core database were"mesenchymal stem cell,scaffold,vascularization".(4)Through the analysis of co-citation and highly cited references,the main concerns were as follows:vascularization strategies:scaffold design,angiogenic factor delivery,in vitro co-culture,and in vivo pre-vascularization.Technology:3D printing,electrospinning,vascular transplantation,vascular fusion.Mechanisms:immune regulation and macrophages,drug/growth factor delivery,the relationship between endothelial cells and osteoblasts,the paracrine relationship between bone cells and endothelial cells,signaling molecular pathways,angiogenesis,and anti-angiogenesis molecules.(5)The researches concerning vascular stimulating scaffolds in bone tissue engineering in and outside China attach great importance to the application of stem cells and 3D printing technology.Current research focuses on biological 3D printing technology,scaffold modification methods,and the development and application of intelligent biomaterials based on bone repair mechanisms.
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BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.