Effect and mechanism of curcumin on skin wound healing and angiogenesis in rats / 中国医师杂志

Objective:To investigate the effect of curcumin on skin wound healing and angiogenesis in rats and its possible mechanism.Methods:Rats with full-thickness dermal defect were prepared and randomly divided into model group, low-dose, medium-dose and high-dose groups of curcumin, with 10 rats in each group. Curcumin was injected intraperitoneally. The low-dose, medium-dose and high-dose groups of curcumin were given 5, 15, 45 mg/(kg·d) curcumin respectively. The rats in the model group were injected intraperitoneally with 0.5% sodium carboxymethyl cellulose for 14 days. The wound healing rate of rats in each group was measured; The wound tissue was stained with haematoxylin and eosin staining, Masson and immunohistochemistry; The levels of angiopoietin-1 (Ang-1) and basic fibroblast growth factor (bFGF) in the wound tissue of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA); The relative expression of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA in wound tissue was detected by real-time quantitative polymerase chain reaction (qRT-PCR); Western blot was used to detect the expression of VEGFA, VEGFR-2, Notch1, Jagged1, Hes1 protein in the wound tissue.Results:The wound healing rate, the vascular density and the level of Ang-1 and bFGF, the mRNA of VEGFA and VEGFR-2, the relative expression of Notch1, Jagged1, Hes1, VEGFA and VEGFR-2 protein in wound tissue of rats in low, medium and high dose groups of curcumin were higher than those in the model group (all P<0.05). Histological staining results showed that the reepithelialization of the wound tissue was not obvious in the model group, with severe infiltration of inflammatory cells and less collagen deposition; the reepithelialization of the wound tissue in the low-dose, medium-dose and high-dose groups of curcumin was gradually obvious, with thickened epidermis, reduced inflammatory cell infiltration and increased collagen deposition. The effect of curcumin on skin wounds in rats was enhanced in a dose-dependent manner (all P<0.05). Conclusions:Curcumin could promote wound healing and angiogenesis in rats, and its mechanism may be related to the activation of Notch signaling pathway.

MiR-26a promotes angiogenesis in rats with cerebral ischemia through PI3K/Akt pathway / 国际脑血管病杂志

Objective:To investigate the effect of miR-26a mediated phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway on angiogenesis in rats with cerebral ischemia.Methods:A total of 100 male SD rats were divided into sham operation group, model group, miR-NC group, and miR-26a group according to the random number table method. The miR-NC group and the miR-26a group were injected with 5 μl miR-26a simulant negative control and miR-26a simulant into the lateral ventricle respectively. The sham operation group and the model group were injected with the same amount of normal saline respectively. The middle cerebral artery occlusion model was induced by the modified intraluminal suture method. In the sham operation group, the thread was only inserted without ligation. Five rats in each group were injected intraperitoneally with 5-bromodeoxyuridine (BrdU) daily for 7 days. Rat brain microvascular endothelial cells (BMECs) cultured and transfected in vitro were divided into control group, oxygen glucose deprivation (OGD) group, miR-NC group, and miR-26a group. The dual luciferase experiment verified the regulatory effect of miR-26a on the phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Longa score was used to detecte the neurological damage of rats. The volume of cerebral infarction was measured by triphenyltetrazolium chloride (TTC) staining. The methyl thiazolyl tetrazolium (MTT) staining, annexin Ⅴ fluorescein isothiocyanate/propidium iodide double staining and tubule formation experiment were used to detect the proliferation, apoptosis and angiogenesis of BMECs, respectively. Real-time fluorescence quantitative reverse transcription polymerase chain reaction was used to detect the miR-26a expression of ischemic brain tissue and BMECs. Immunofluorescence double labeling method (BrdU/von Willebrand factor [vWF]) was used to detect the proliferation of rat vascular endothelial cells. Western blot analysis was used to detect the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), PTEN, PI3K and Akt protein in ischemic brain tissue.Results:Bioinformatics and dual luciferase experiments verified the targeted regulation of PTEN by miR-26a. Compared with the sham operation group, the expression of miR-26a, VEGF, bFGF, Ang-2, PI3K, AKT and the number of BrdU + /VWF + cells in ischemic brain tissue in the model group and miR-NC group increased, while the expression of PTEN decreased (all P<0.05). Compared with the model group, the effect of various indexes in the miR-26a group was more significant (all P<0.05). Compared with the control group, the proliferation and angiogenesis of BMECs in the OGD group and the miR-NC group were significantly increased, and the apoptosis was significantly reduced (all P<0.05). Compared with the OGD group, the effect of various indexes in the miR-26a group was more significant (all P<0.05). Conclusion:miR-26a can mediate the targeted inhibition of PTEN expression, up-regulate angiogenesis related factors (VEGF, bFGF and Ang-2), and promote vascular endothelial cell proliferation and angiogenesis in rats with cerebral infarction by activating PI3K/Akt signaling pathway.

Targeted contrast enhanced ultrasound for in vivo quantitative evaluation on angiogenesis in transplanted ovarian of rats / 中国医学影像技术

Objective: To observe the value of targeted contrast enhanced ultrasound (CEUS) using anti-Mullerian canal hormone (AMH) targeted nanobubbles (AMH-NB) for in vivo quantitative evaluation on ovarian neovascular density after ovarian auto-transplantation in SD rats. Methods: The nanobubbles carrying anti-AMH antibody were prepared, and their basic physical properties were examined. Then ovarian auto-transplantation rat models were established. The targeted (AMH-NB), non-targeted (N-NB) contrast agents and SonoVue were administered on the 7th day after transplantation to obtain peak intensity (PI) and time to peak (TTP). The microvascular density (MVD) was measured using immunohistochemistry, and the correlation of PI, TTP and MVD were analyzed. Results: The particle size of AMH-NB uniformly distributed, ranged (622.67±33.65)nm, and the concentration of AMH-NB was (2.90±0.26)×108/ml. PI of ovarian angiography with AMH-NB was (7.93±0.65)dB and TTP was (42.53±1.74)s, with N-NB was (6.14±0.44)dB and (54.35±1.73)s, with Sonovue was (4.15±0.83)dB and (28.71±1.18)s, respectively (all P<0.05).Immunohistochemical analysis showed that the microvascular density was (61.20±6.84)/HP, histological analysis indicated that AMH-NB were able to penetrate blood vessels to the interstitial space and combine with AMH. PI, TTP of AMH-NB were highly both correlated with MVD (r=0.84, r=-0.84, both P<0.05). Conclusion: AMH-NB can be used to qualitatively and quantitatively evaluate the angiogenesis in transplanted ovarian of rats in vivo with CEUS.

Red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells / Própolis vermelha e L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256

ABSTRACT Objective: To evaluate the effect of red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells. Methods: The study consisted of two experiments with four groups each (total: 57 hamsters). In the experiment 1, the animals were inoculated with Walker tumor cells, followed by administration of test substances (red propolis 200mg/5mL/kg or L-lysine 150mg/kg) or control substances (gum arabic 5mL/kg or water 5mL/kg) for 10 days. The animals in the experiment 2 received red propolis, L-lysine, gum arabic or water at the same doses, for 33 days prior to inoculation of Walker tumor cells, followed by 10 days of treatment with the same substances. Based on single-plane images, angiogenesis was quantified (mean vascular area), in percentage, and tumor area (mm2) and perimeter (mm). Results: In the experiment 1, compared to animals receiving water, the mean vascular area expressed in percentage was significantly smaller in animal treated with propolis (p<0.05) and L-lysine (p<0.001). Conclusion: Both red propolis and L-lysine inhibited tumor angiogenesis in the new hamster cheek pouch model when administered after tumor inoculation.

RESUMO Objetivo: Avaliar o efeito da própolis vermelha e da L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256. Métodos: O estudo consistiu em dois experimentos com quatro grupos cada (total: 57 hamsters). No experimento 1, os animais foram inoculados com células de tumor de Walker, tendo em seguida administradas as substâncias teste (própolis vermelha 200mg/5mL/kg ou L-lisina 150mg/kg) ou controle (goma arábica 5mL/kg ou água 5mL/kg) por 10 dias. Os animais do experimento 2 receberam própolis vermelha, L-lisina, goma arábica ou água nas mesmas doses, por 33 dias antes do inóculo das células de tumor de Walker, seguido por 10 dias de tratamento com as mesmas substâncias. Baseado em imagens em plano único, foram quantificados a angiogênese (área vascular média), em termos percentuais, e a área (mm2) e o perímetro (mm) do tumor. Resultados: Comparada aos animais que receberam água, a área vascular média, expressa em percentagem, foi significativamente menor nos animais tratados com própolis (p<0,05) e com L-lisina (p<0,001). Conclusão: Tanto a própolis vermelha quanto a L-lisina inibiram a angiogênese no novo modelo de bolsa jugal de hamsters, quando administradas após a inoculação do tumor.

TNF-alpha increases angiogenic potential in a co-culture system of dental pulp cells and endothelial cells

Abstract We recently demonstrated that a co-culture system of human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs) could enhance angiogenesis ability in vitro. However, whether tumor necrosis factor α (TNF-α) could promote blood vessel formation during pulp regeneration remained unknown. The aim of this study was to investigate the effects of TNF-α on the formation of endothelial tubules and vascular networks in a co-culture system of hDPSCs and HUVECs. hDPSCs were co-cultured with HUVECs at a ratio of 1:5. The Matrigel assay was performed to detect the total tubule branching lengths and numbers of branches, and the Cell-Counting Kit 8 assay was performed to examine the effect of TNF-α on cell proliferation. Real-time polymerase chain reactions and western blot were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression. The Matrigel assay showed significantly greater total branching lengths and numbers of branches formed in the experimental groups treated with different concentrations of TNF-α compared with the control group. The decomposition times of the tubule structures were also significantly prolonged (P < 0.05). Treatment with 50 ng/ml TNF-α did not significantly change the proliferation of co-cultured cells, but it significantly increased the VEGF mRNA and protein expression levels (p < 0.05). In addition, the migration abilities of HUVECs and hDPSCs increased after co-culture with TNF-α (p < 0.05). TNF-α enhanced angiogenic ability in vitro in the co-culture system of hDPSCs and HUVECs.

Neovascular maturity: the intervention target of vulnerable atherosclerotic plaques / 国际脑血管病杂志

Immature neovascularization in atherosclerotic plaques is closely associated with plaque vulnerability. Pathological factors with inflammation as the core in the plaques interfere with the formation of junction between endothelial cells, parietal cell coverage and basement membrane deposition, hindering the maturation of neovascularization. Improving neovascular maturity is a potential intervention target for stabilizing vulnerable atherosclerotic plaques.

Bioinformatics analysis of angiogenesis-related miRNAs in endothelial progenitor cell exosomes / 中国医师杂志

Objective By taking usage of bioinformatics screening methods,this medical research aimed at exploring how the miRNAs in endothelial progenitor cell exosomes relate to the regulation of angiogenesis.Methods miRNAs in endothelial progenitor cells exosomes and angiogenesis-related miRNA was intersected from the existing database to obtain the candidates of miRNA molecules related to angiogenesis in endothelial progenitor exosomes.Results 160 and 50 miRNAs in endothelial progenitor cell candidates were obtained through experimental data analysis and literature searching respectively.600 candidates of angiogenesis-related miRNAs were obtained through literature searching;the top 20 with the highest frequency were selected out.Finally,9 miRNA candidates (miR-126,miR-21,miR-221,miR-92a,miR-199a,miR-210,miR-214,miR-155,miR-146a) that may be highly expressed in endothelial progenitor exosomes and associated with angiogenesis were obtained for the following research.Conclusions Based on data analysis and literature searching,bioinformatics could screen out the target miRNAs for follow-up studies easily and reliably,it is worthy to be widely applied and popularized.

Collateral vessel remodeling after ischemic stroke: cellular and molecular mechanisms / 国际脑血管病杂志

Ischemic stroke has the characteristics of high disability,high mortality,and high recurrence rate,and the abundant collateral circulation is an independent predictor of good outcomes in stroke.This article mainly elaborates the cytological and molecular mechanisms of vascular remodeling process after ischemic stroke in order to provide new ideas and targets for the treatment of ischemic stroke.

Advances in tracheal transplantation / 中华耳鼻咽喉头颈外科杂志

The length of tracheal defect or stenosis exceeded 5 cm could not be treated by simple resection and end-to-end anastomosis of the remaining trachea. Various ways of tracheal replacement had appeared sequentially, such as radial forearm free flap with cartilage grafts, tracheal tissue-engineering and tracheal allotransplantation. Among these methods, tracheal allotransplantation displayed a better long-term result. In this review, we are focused on recent advances in tracheal allotransplantation, particularly on revascularization and reepithelialization of graft, as well as on the application of immunosuppressive agents.

Mechanism of collateral artery growth / 心血管康复医学杂志

Promoting collateral artery growth is an important way to treat myocardial ischemia and other ischemic diseases. Researches indicate that rise of shear stress of vessel is an early activator of collateral artery growth, which can trigger a series of reactions to promote collateral artery growth. The present article also mainly summarized cells and chemical factors involved in process of collateral artery growth, including monocytes, smooth muscle cells, monocyte chemoattractant protein and fibroblast growth factor etc., and their roles in collateral artery growth.

MicroRNAs: a therapeutic target for ischemic stroke / 国际脑血管病杂志

Ischemic stroke is a common neurological disease. MicroRNAs not only play an important role in acute phase of ischemic stroke, but also regulate neurogenesis and angiogenesis after stroke. This article reviews the research progress and prospects of microRNAs as a therapeutic target for ischemic stroke.

Role and mechanism of heme oxygenase-1 in cerebral ischemia-reperfusion injury / 国际脑血管病杂志

Heme oxygenase (HO) -1 is the most bioactive HO type. It reduces tissue damage by exerting antioxidant, anti-inflammatory, and cytoprotective effects during ischemia-reperfusion injury. It is considered to be a new direction for the treatment of ischemia-reperfusion injury. This article reviews the role of HO-1 in ischemia-reperfusion injury and its possible mechanisms.

Vascular endothelial growth factor: a potential therapeutic target for ischemic stroke / 国际脑血管病杂志

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and vascular regeneration after cerebral ischemia.On one hand,VEGF plays a neuroprotective effect by promoting angiogenesis and neurogenesis;on the other hand,VEGF induced endothelial permeability can cause blood-brain barrier (BBB) dysfunction.Exercise preconditioning can up-regulate the expression of VEGF and reduce the ischemic brain damage by enhancing the cerebral microvascular integrity.VEGF can be used as a therapeutic target for ischemic stroke.

Advances in the research of role of integrin-linked kinase in angiogenesis / 中华烧伤杂志

Integrin-linked kinase (ILK) has been found for twenty years, and its biological characteristics have been extensively studied by multi-discipline. At present, studies of ILK are mainly focused on its roles in angiogenesis, tumor formation, and tissue fibrosis, etc. In recent years, the regulation effect of ILK in angiogenesis attracts attention of researchers. The studies showed that ILK can stimulate the secretion of angiogenic factor, promote the proliferation and migration of endothelial cells and inhibit their apoptosis, and therefore play an important role in the regulation of angiogenesis. Further research on molecular mechanism about the role of ILK playing in angiogenesis may provide an effective method for the treatment of some diseases.

Application of cell sheet technology in tissue engineering / 中国组织工程研究

BACKGROUND:The cel sheet technology that is applied with the absence of scaffolds and enzymatic digestion can effectively repair tissue defects and improve organ function, by stimulating the secretion of extracelular matrix to form a dense membrane tissue. OBJECTIVE: To review the recent progress in cel sheet technology used in tissue engineering, thereby providing a new idea for relevant basic and clinical research. METHODS:The first author retrieved CNKI database, Wanfang database and PubMed with the keywords of “cel sheet, tissue engineering” in Chinese and English, respectively. Literature retrieval period was from January 2010 to July 2015. RESULTS AND CONCLUSION:Cel sheet technology combined with scaffold materials can be used for reconstruction and repair of tissues and organs. With the emerging of new technologies, multi-layer cel sheets are stratified to form a three-dimensional tissue for repair of soft tissues and organs. Compared with the monolayer cel sheet, the three-dimensional cel sheet that is laminated by same or different cel sheets has stronger regenerative ability and can be used to construct the ideal target tissue modelin vitro. Cel sheet technology combined with scaffolds can improve the mechanical strength of the composite and reduce cel loss, which has made great progress in the repair of tooth, bone and cartilage tissue. Currently, the cel sheet technology is at the laboratory stage, and little is reported on its clinical applications. We look forward to more innovative technologies that can be integrated into the cel sheet technology.

The effect and mechanism of naringin on callus angiogenesis of ovariectomized rats' fractures / 中华骨科杂志

Objective To explore the angiogenesis&neovascularization effects of naringin treatment in ovariectomized rats’fracture healing. Methods Upper 1/3 transverse tibial fracture model 4 weeks later after ovariectomized were estimated and randomly divided into the naringin group and control group. Microfil perfusion technique was used to analysis the angiogene?sis situation at two weeks after bone fracture. HE staining was used to evaluate the level of angiogenesis&neovascularization of tis?sue from histological point of view. The relative expression of VEGF in the callus was identified by real?time polymerase chain re?action. Immunohistochemical technique was used to observe the vessel endothelial growth factor?2 in the callus of the two groups. Maximum fracture load was tested by three?point bend test. Results The vascular volume and vascular density were more in nar?ingin group than control group. The HE staining of the 2 week group slices shows that the VA, VN2 of the unit of high magnifica?tion vision of the naringin group was significantly larger compared to the control group. Real?time PCR revealed that the compara?tive expression of VEGF is more in naringin group than in control group; the positive number of VEGFR?2 is more in naringin group than in control group. Naringin can promote the maximum load of the callus. Conclusion Naringin can promote ovariecto?mized rats’angiogenesis&neovascularization in the early process of fracture healing. It may be act on the signaling pathway of VEGF/VEGFR?2.

Autologous endothelial progenitor cells promote the neovascularization of tissue engineering bone in vitro and vivo / 重庆医学

Objective Investigate the ability of autologous endothelial progenitor cells (EPCs) in promoting the neovascular-ization of tissue engineering bone in vitro and vivo .Methods Co-culture EPCs drived from autologous peripheral blood and mesen-chymal stem cells drived from bone marrow (BMSCs) at the best proportion of 1 ∶ 2 which was the largest cell proliferation rate in vitro ,osteogenesis related cytokines Osteonectin ,Osteopotin ,Collagen Type 1(Col-1) and angiogenesis related cytokine VEGF in vitro by using real-time quantitative polymerase chain reaction(PCR) ,and compared with pure EPCs and BMSCs groups at 3rd ,7th and 14th day ;the tissue engineering bone seeded with EPCs ,BMSCs and co-culture cells (EPCs ∶ BMSCs = 1 ∶ 2) were transplanted into rabbit limbs muscle ,the growing states of tissue engineering bone were observed at 2 ,4 and 8 weeks after transplantation ,at the same time the expression of CD34 ,CD105 and ZO-1 were detected with immunohistochemistry staining .Results The mRNA expression of Osteonectin ,Osteopotin ,Col-1 and VEGF were gradually increased when detected at 3rd ,7th and 14th day with real-time PCR ,and the co-culture cells group increased most obviously in the three groups in vitro at the same period time(P< 0 .01) ;The microvascularization of the engineering biological bone were observed in vivo with immunohistochemistry ,and neovasculariza-tion of co-culture cells group was also the most obvious group in three groups ,immunohistochemical showed that CD34 ,CD105 and ZO-1 was also higher than the other two groups(P< 0 .01) .Conclusion Autologous EPCs interact with BMSCs could promote vas-cularization of tissue engineering bone both in vivo and in vitro .

Cells involved in extracellular matrix remodeling after acute myocardial infarction / Células envolvidas no remodelamento da matriz extracelular após infarto agudo do miocárdio

Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation. Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct. .

Objetivo Avaliar os efeitos da transferência gênica do VEGF165 no processo de remodelamento da matriz extracelular após infarto agudo do miocárdio. Métodos Ratos Wistar foram submetidos ao infarto do miocárdio por ligação da artéria coronária descendente esquerda, e a fração de ejeção de ventrículo esquerdo foi utilizada para classificar os infartos em grandes e pequenos. Os animais foram divididos em grupos de dez animais, de acordo com o tamanho do infarto (grande ou pequeno), e receberam ou não tratamento com o VEGF165. A avaliação dos diferentes marcadores foi realizada por imuno-histoquímica e quantificação digital. Os anticorpos primários utilizados foram antifibronectina, antivimentina, anti- CD44, anti-E-caderina, anti-CD24, anti-alfa-1-actina e anti-PCNA. Os resultados foram representados como média e erro padrão, e analisados por ANOVA, sendo considerado estatisticamente significativo se p≤0,05. Resultados Houve aumento significativo da expressão de marcadores de células indiferenciadas, como fibronectina (proteína presente na matriz extracelular) e CD44 (glicoproteína presente nas células endoteliais). Entretanto, houve diminuição da expressão de vimentina e PCNA, indicando possível diminuição do processo de proliferação celular após o tratamento com VEGF165. Os marcadores de células diferenciadas, E-caderina (proteína de adesão entre as células do miocárdio), CD24 (proteína presente nos vasos sanguíneos) e alfa-1-actina (marcador especifico de miócitos) também apresentaram maior expressão nos grupos submetidos à terapia gênica, comparativamente com o grupo não tratado. O valor obtido pela relação entre alfa-1-actina e vimentina foi aproximadamente três vezes maior nos grupos tratados com VEGF165, indicando maior diferenciação tecidual. Conclusão O papel dos miócitos se mostrou importante no processo de remodelamento tecidual, confirmando que o VEGF165 parece conferir um efeito protetor no tratamento do infarto agudo do miocárdio. .

Potential therapeutic roles of endothelial progenitor cells for ischemic stroke / 国际脑血管病杂志

Increasing studies have shown that endothelial progenitor cel s can not only promote the damaged endothelial cel s and vascular repair in ischemic brain tissue, but also promote neurogenesis, and thus promote neurological function recovery. Endothelial progenitor cel s transplantation may become an effective approach for the treatment of ischemic stroke.

The effect of different pore sized hydroxyapatite for promoting bone vascularization in tissue engineering / 重庆医学

Objective To investigate the effect of different pore sized hydroxyapatite for promoting bone vascularization in tissue engineering.Methods Male Wistar rats were randomly divided into three groups,named group A,B and C,which were im-planted hydroxyapatite bioceramics compositing 4 μg bone morphogenetic protein with different aperture of 200 -300,350 -450, 500-600 μm in the back subcutaneously.The size of each block was 5 mm×5 mm×1 mm in a weight about of 40.0 mg.After im-plantation,the animals were killed and the implants and the surrounding tissue were taken out at the first,second,third and forth week respectively.HE staining of histological analysis was used to detect the situation of local neovascularization.Results There was significant difference between second and third week in group A.Comparing the area of vascularization at different time points in group B and group C,there were significant difference in the comparison of intragroup (P <0.05 ).During the first week after surgery,there was only group C that had the area of vascularization.During the second and forth week after operation,the area of vascularization in group B and group C were significant higher than group A (P <0.05).The C group showed a great deal of new-born blood vessels and clear formation of bone trabeculae.Conclusion The hydroxyapatite bioceramics of 500-600 μm could better promote vascalarization of tissue engineering in bone.