3D打印功能化复合水凝胶支架用于乳腺癌治疗及脂肪再生
批准号:
32101090
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
马红石
依托单位:
学科分类:
生物材料与生物效应
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
马红石
中文摘要
乳腺恶性肿瘤对全球不同年龄段的女性都会造成威胁,切除手术后造成乳腺缺损,同时可能有肿瘤细胞残余。放/化疗作为辅助疗法,会给人体带来一定毒副作用。因此,亟需构建兼具修复受损乳腺脂肪组织,同时有效抑制乳腺癌转移复发的双功能生物活性材料。本项目拟采用3D打印技术构建GelMA-树枝状介孔二氧化硅(DMSNs)复合水凝胶支架材料,其中可降解的DMSNs包裹了靶向小分子抗癌药物,通过改变复合水凝胶组成及结构实现靶向药物及无机功能离子的可控释放。阐明复合水凝胶支架在体外、体内抑制肿瘤生长、转移的效果及作用机制。并重点探究复合水凝胶支架通过可控释放的功能无机Si离子在体内促进脂肪再生、血管生成的效果,阐明复合水凝胶支架的组成及结构与肿瘤治疗、脂肪再生、血管生成之间的构效关系。最终,实现构建一种新颖的功能化复合水凝胶支架,兼具乳腺癌治疗与脂肪再生的的功效,其具有用于临床上治疗乳腺癌的潜在前景。
英文摘要
Breast malignancies pose a threat to women of all ages around the world. Surgery may lead to breast defects, followed by possible residual tumor cells. As adjuvant therapy treatments, radiotherapy/chemotherapy will bring certain toxic and side effects to human body. Therefore, it is urgent to construct bifunctional bioactive biomaterials that can repair the damaged breast adipose tissue after surgical resection and effectively inhibit breast cancer metastasis and recurrence. This project intends to construct a 3D printing composite hydrogel scaffold of GelMA-dendritic mesoporous silica nanoparticles (DMSNs), in which targeted small molecule anticancer drugs were integrated. Controlled release of targeted drugs and inorganic functional ions can be realized by changing the composition and structure of the composite hydrogel scaffolds. The effect and mechanism of composite hydrogel scaffolds in inhibiting tumor growth and metastasis in vitro and in vivo will be elucidated. Furthermore, the effects of controllable release of Si ions of the composite hydrogel scaffolds on promoting adipose regeneration and angiogenesis in vivo will be explored. In addition, the relationship between the composition and structure of the composite hydrogel scaffolds and tumor therapy, adipose regeneration and angiogenesis will be clarified. Finally, a novel functional composite hydrogel scaffold will be constructed, which has the efficacy of both breast cancer treatment and adipose regeneration, having a potential prospect for clinical treatment of breast cancer.
临床上乳腺癌最常用的治疗方法是手术结合放/化疗,其中,手术切除会造成组织缺损,同时存在肿瘤复发的危险。放/化疗会给人身体带来毒副作用。针对乳腺癌目前临床上治疗方法面临的难点问题,本项目提出将肿瘤疾病治疗与组织修复相结合的思路,突破传统生物材料仅具有单一组织修复的功能,赋予复合水凝胶支架肿瘤治疗与脂肪再生双功能性,在乳腺癌临床治疗上具有潜在应用前景。.本项目成功合成形貌可控的硅酸钙纳米线,采用3D打印技术,实现构建功能化复合水凝胶支架用于乳腺癌术后肿瘤治疗以及脂肪组织修复。通过改变复合水凝胶的组成,实现对其流变学性能、力学性能、降解性能等关键理化性能调控。探究功能化复合支架有效杀死乳腺癌细胞、抑制体内肿瘤生长疗效。同时,发现水凝胶支架为脂肪来源干细胞提供粘附位点,揭示持续释放活性功能Si离子刺激了PI3K和Akt信号通路的蛋白磷酸化水平,显著提高成脂相关基因(FABP4, leptin, adiponection)及蛋白的表达,进而促进脂肪干细胞成脂分化,以及体内脂肪组织再生。因此,这种新型的双功能水凝胶支架能够有效修复乳腺癌手术导致的脂肪组织缺损,同时杀死可能残余的乳腺癌细胞。复合支架具有作为生物活性治疗平台的潜力,可以克服传统植入物的局限性,在乳腺癌手术切除后乳腺肿瘤患者的治疗中具有潜在的应用前景。
3D 打印黑色生物陶瓷:兼具疾病治疗与组织再生
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批准号:21ZR1472600
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项目类别:省市级项目
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资助金额:0.0万元
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批准年份:2021
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负责人:马红石
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依托单位:
国内基金
海外基金