3D打印智能材料Li-Cu-n-HA/ColⅠ协同SDF1-CXCR4调控干细胞归巢治疗ONFH研究
批准号:
81672165
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
康鹏德
依托单位:
学科分类:
H0604.骨、关节、软组织损伤与修复
结题年份:
2020
批准年份:
2016
项目状态:
已结题
项目参与者:
谢小伟、杨周源、岳辰、王浩洋、李东海、杨旭、唐家源
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中文摘要
股骨头坏死发生发展与局部bMSCs和成骨细胞数量减少、活性下降导致血管生成、骨修复停滞相关。SDF-1α-CXCR4生物轴调控体内干细胞向组织损伤处迁移、归巢,锂调控经典Wnt信号通路促进MSCs/HCPs成骨,铜调控HIF-1/ PHD/VEGF信号通路促进内皮细胞成血管分化;具有生物活性的智能生物材料是骨组织工程研究的热点和方向。基于干细胞与新型智能生物材料的协同以及前期锂促进成骨研究成果,将锂、铜掺入n-HA/ColⅠ并通过3D打印设计具有生物活性的智能材料Li-Cu/n-HA/ColⅠ,并携载SDF-1α缓释微球,动员、诱导MSCs/HCPs定向迁移、归巢至植入材料部位,智能生物材料所具有的持久、有效的生物物理信号调控归巢的MSCs/HCPs成骨、成血管,修复死骨清除后的骨缺损、重建股骨头力学性能,避免股骨头塌陷,为早期股骨头坏死的保头治疗提供新的、有效地治疗方法。
英文摘要
The pathogenesis of osteonecrosis of femoral head (ONFH) has been reported to be associated with suppression of mesenchymal stem cells (MSCs) and osteoblast in the bone marrow, which inhibits angiogenesis and bone repair of local necrotic lesion. In recent years the SDF-1α/CXCR4 pathway has been widely studied and evidence demonstrates that the SDF-1α–CXCR4 signaling pathway was involved in mobilization and recruitment of MSCs and endothelial progenitor cells (EPCs) after tissue injury. Our previous studies also found that local application of lithium could accelerate bone regeneration by Wnt signal-mediated osteoblastogenesis through regulating proliferation and differentiation of local MSCs. Additionally, the recent researches have revealed that copper can promote vascularization of vascular endothelial cells or EPCs through HIF-1/PHD/VEGF signaling pathway, thus contributing to formation of new bones in necrotic zones. With rapid advances in 3D printed bone tissue engineering scaffolds, smart biomaterials have increasingly become the focus of research in recent years. Based on the synergism of stem cell biologiy and smart biomaterials and lithium- copper mediated neo-angiogenesis and osteogenesis, it reasonable to assume that a new promising smart biomaterials, consisting of 3D printed lithium- copper –doped nano hydroxyapaptite/collagen bone tissue engineering scaffolds composite with controlled-release SDF-1α microspheres, could be designed to rebuild biomechanical support of necrotic lesion in femoral head, and therefore prevent the collapse of femoral head, by pro-angiogenic and pro-osteogenic repair effects resulting from mobilization and recruitment of MSCs and EPCs, activation of canonical Wnt signaling pathway and excellent osteoconduction of 3D printed bone engineering tissue engineering scaffolds.
股骨头坏死发生发展与局部bMSCs和成骨细胞数量减少、活性下降导致血管生成、骨修复停滞相关。SDF-1α-CXCR4生物轴调控体内干细胞向组织损伤处迁移、归巢,锂调控经典Wnt信号通路促进MSCs/HCPs成骨,铜调控HIF-1/ PHD/VEGF信号通路促进内皮细胞成血管分化,并且铜具有上调SDF-1α表达从而发挥调控细胞归巢的潜能;具有生物活性的智能生物材料是骨组织工程研究的热点和方向。基于干细胞与新型智能生物材料的协同以及前期锂促进成骨研究成果,将锂、铜掺入n-HA并设计具有生物活性的智能材料Li-Cu/n-HA支架,探讨了Cu动员、诱导MSCs/HCPs定向迁移、归巢至植入材料部位,智能生物材料所具有的持久、有效的生物物理信号调控归巢的MSCs/HCPs成骨、成血管,修复清除死骨后的骨缺损、重建股骨头力学性能,避免股骨头塌陷,为早期ONFH的保头治疗提供新的、有效地治疗方法。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Repair of the calvarial defect in goat model using magnesium-doped porous hydroxyapatite combined with recombinant human bone morphogenetic protein-2
掺镁多孔羟基磷灰石联合重组人骨形态发生蛋白2修复山羊模型颅骨缺损
DOI:10.3233/bme-171678
发表时间:2017-01-01
期刊:BIO-MEDICAL MATERIALS AND ENGINEERING
影响因子:1
作者:Deng, Liqing;Li, Donghai;Kang, Pengde
通讯作者:Kang, Pengde
DOI:doi: 10.3892/ijo.2019.4914.
发表时间:2020
期刊:INTERNATIONAL JOURNAL OF ONCOLOGY
影响因子:5.2
作者:Zhao xin;Yuying Fang;Xingwen Wang;Zhouyuan Yang;Donghai Li;Tian Meng;Pengde Kang
通讯作者:Pengde Kang
Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium- hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold (Retracted article. See APR, 2023)
多孔纳米锂羟基磷灰石/明胶微球/促红细胞生成素复合支架增强糖皮质激素所致股骨头坏死骨缺损修复效果
DOI:10.1039/c7bm00975e
发表时间:2018-03-01
期刊:BIOMATERIALS SCIENCE
影响因子:6.6
作者:Li, Donghai;Xie, Xiaowei;Kang, Pengde
通讯作者:Kang, Pengde
In vivo evaluation of porous lithium-doped hydroxyapatite scaffolds for the treatment of bone defect
多孔锂掺杂羟基磷灰石支架治疗骨缺损的体内评价。
DOI:10.3233/bme-181018
发表时间:2018-01-01
期刊:BIO-MEDICAL MATERIALS AND ENGINEERING
影响因子:1
作者:Luo, Yue;Li, Donghai;Kang, PengDe
通讯作者:Kang, PengDe
DOI:doi: 10.1111/jcmm.16103.
发表时间:2020
期刊:JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
影响因子:5.3
作者:Xin Zhao;Mohammed Alqwbani;Yue Luo;Changjun Chen;Ge A;Yang Wei;Donghai Li;Qiuru Wang;Meng Tian;Pengde Kang
通讯作者:Pengde Kang
rSC-EXO/NGF/Li-hydrogel调控神经-骨免疫成骨修复股骨头坏死研究
- 批准号:82372392
- 项目类别:面上项目
- 资助金额:49万元
- 批准年份:2023
- 负责人:康鹏德
- 依托单位:
MiR-155-CCL22@TDN-Apt调控Treg介导骨免疫成骨与股骨头坏死研究
- 批准号:82172414
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2021
- 负责人:康鹏德
- 依托单位:
MWCNT气凝胶调控M2介导骨免疫促进激素性股骨头坏死修复研究
- 批准号:81974333
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2019
- 负责人:康鹏德
- 依托单位:
锂盐对Wnt通路的调控及掺锂盐多孔n-HA/胶原复合BMSCs治疗股骨头坏死研究
- 批准号:81271976
- 项目类别:面上项目
- 资助金额:70.0万元
- 批准年份:2012
- 负责人:康鹏德
- 依托单位:
DKK-1基因沉默对Wnt信号通路的调控及对激素性股骨头坏死的防治研究
- 批准号:81171763
- 项目类别:面上项目
- 资助金额:60.0万元
- 批准年份:2011
- 负责人:康鹏德
- 依托单位:
PLGA-NP介导Runx2基因转染骨髓脂肪细胞转分化为成骨细胞治疗股骨头坏死研究
- 批准号:30772202
- 项目类别:面上项目
- 资助金额:28.0万元
- 批准年份:2007
- 负责人:康鹏德
- 依托单位:
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