3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels.
3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels.
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DOI：
10.1016/j.actbio.2021.03.030
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发表时间：
2021-05
影响因子：
9.7
通讯作者：
Ravindran S
中科院分区：
文献类型：
--
作者：
Huang CC;Kang M;Shirazi S;Lu Y;Cooper LF;Gajendrareddy P;Ravindran S
间充质干细胞(MSC)来源的细胞外小泡(EV)以其幼稚和工程化的形式出现，成为干细胞治疗的潜在替代品。虽然它们具有明确的治疗潜力，但在体内对其活性的空间和时间控制仍然是一个挑战。这项研究的目的是设计一种方法，将电动汽车包裹在3D水凝胶中，以延长给药时间。为了实现这一点，我们利用了MSC EV与ECM蛋白质及其衍生肽的相互作用。利用来自MSCs的骨诱导功能工程EVS(Fees)，我们发现Fees与来自胶原(DGEA，GFPGER)和纤维连接蛋白(RGD)的模拟多肽结合。在体外实验中，含有RGD的可光交联性藻酸盐水凝胶能够在7天内包裹、锚定和保留费用，同时保持EVS的结构完整性和骨诱导功能。当在活体颅骨缺损模型中使用时，与没有费用的对照组相比，含有费用的海藻酸盐-RGD水凝胶将骨再生促进了4倍，与没有系链肽的对照组相比增加了2倍。这些结果表明，电动汽车可以被拴在生物材料上，以促进骨修复和体内延长给药的重要性。这一结果也为该技术可能用于其他再生医学应用的电动汽车的受控递送提供了前奏。
Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naïve and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery. To achieve this, we have leveraged the MSC EV interactions with ECM proteins and their derivative peptides. Using osteoinductive functionally engineered EVs (FEEs) derived from MSCs, we show that FEEs bind to mimetic peptides from collagen (DGEA, GFPGER) and fibronectin (RGD). In in vitro experiments, photocrosslinkable alginate hydrogels containing RGD were able to encapsulate, tether and retain the FEEs over a period of 7 days while maintaining the structural integrity and osteoinductive functionality of the EVs. When employed in a calvarial defect model in vivo, alginate-RGD hydrogels containing the FEEs enhanced bone regeneration by a factor of 4 compared to controls lacking FEEs and by a factor of 2 compared to controls lacking the tethering peptide. These results show that EVs can be tethered to biomaterials to promote bone repair and the importance of prolonged delivery in vivo. Results also provide a prelude to the possible use of this technology for controlled delivery of EVs for other regenerative medicine applications.
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影响因子：
14
作者：
Narayanan K;Kumar S;Padmanabhan P;Gulyas B;Wan ACA;Rajendran VM
通讯作者：
Rajendran VM
用于软骨和骨组织工程的可注射水凝胶
影响因子：
12.7
作者：
Liu M;Zeng X;Ma C;Yi H;Ali Z;Mou X;Li S;Deng Y;He N
通讯作者：
He N
影响因子：
4.1
作者：
Garske, Daniela S.;Schmidt-Bleek, Katharina;Cipitria, Amaia
通讯作者：
Cipitria, Amaia
影响因子：
12.4
作者：
Lv, Kaiqi;Li, Qingju;Hu, Xinyang
通讯作者：
Hu, Xinyang
整联蛋白和外泌体，是癌症进展的危险联络。
影响因子：
5.2
作者：
Paolillo M;Schinelli S
通讯作者：
Schinelli S