In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion.
In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion.
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通过低温自由挤压制造的基于 ECM 的支架顺序输送适体和 BMP2 进行原位骨再生
DOI：
10.1016/j.bioactmat.2021.04.013
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发表时间：
2021-11
影响因子：
18.9
通讯作者：
Xiong Z
中科院分区：
文献类型：
--
作者：
Sun T;Meng C;Ding Q;Yu K;Zhang X;Zhang W;Tian W;Zhang Q;Guo X;Wu B;Xiong Z
原位组织工程是治疗骨缺损的有效方法。它可以克服传统骨组织工程的局限性，传统骨组织工程通常涉及广泛的细胞扩增步骤，移植后细胞存活率低，以及免疫排斥的风险。在此，通过低温自由形式挤出制造多孔支架聚己内酯（PCL）/脱细胞小肠粘膜下层（SIS），然后用适体和PIGF-2123-144* 融合的BMP 2（pBMP 2）进行表面修饰。这两种生物活性分子依次递送。适体Apt 19 s对骨髓间充质干细胞（BMSCs）表现出结合亲和力，可快速释放，促进宿主BMSCs的动员和招募。与PlGF-2123-144肽融合的BMP 2（其显示出对ECM基质的“超亲和力”）以缓慢和持续的方式释放，诱导BMSC成骨分化。体外实验结果表明，PCL/SIS-pBMP 2-Apt 19 s的顺序释放促进了细胞的迁移、增殖、碱性磷酸酶活性和成骨相关基因的mRNA表达。体内实验结果表明，与PCL/SIS-BMP 2-Apt 19 s的顺序释放系统相比，PCL/SIS-BMP 2-Apt 19 s的顺序释放系统明显增加了大鼠颅骨临界尺寸缺损中的骨形成。因此，新的递送系统显示出作为实现基于无细胞支架的原位骨再生的理想替代方案的潜力。本研究设计了PCL/SIS-pBMP 2-Apt 19 s的序贯释放系统，以促进内源性干细胞归巢和成骨分化。·与趋化因子、生长因子和肽相比，适体Apt 19 s可以特异性靶向内源性干细胞BMSC并有效地募集细胞归巢。·PlGF-2123-144结构域插入BMP 2（pBMP 2）赋予对基于ECM的材料的超亲和力。因此，pBMP 2在基于ECM的材料中具有高的保留率，并且具有从基于ECM的递送系统的控制释放曲线。·新型支架PCL/SIS-pBMP 2-Apt 19 s实现了原位无细胞支架骨再生。
In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ. In current study, a sequential release system of PCL/SIS-pBMP2-Apt19s was designed to promote the homing and osteogenic differentiation of endogenous stem cells. •Compared with chemokines, growth factors, and peptides, aptamers Apt19s could specifically target endogenous stem cells BMSC and efficiently recruit cell homing. •The insertion of the PlGF-2123-144 domain to BMP2 (pBMP2) confers a super affinity to ECM-based materials. Thus, pBMP2 has a high ratio of retain in ECM-based materials, and possess a control release profile from ECM-based delivery system. •The novel scaffold PCL/SIS-pBMP2-Apt19s achieves cell-free scaffold-based bone regeneration in situ.
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影响因子：
15.1
作者：
Lienemann, Philipp S.;Vallmajo-Martin, Queralt;Ehrbar, Martin
通讯作者：
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影响因子：
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56.9
作者：
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