Development of a Bone-Mimetic 3D Printed Ti6Al4V Scaffold to Enhance Osteoblast-Derived Extracellular Vesicles' Therapeutic Efficacy for Bone Regeneration.
Development of a Bone-Mimetic 3D Printed Ti6Al4V Scaffold to Enhance Osteoblast-Derived Extracellular Vesicles' Therapeutic Efficacy for Bone Regeneration.
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DOI：
10.3389/fbioe.2021.757220
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发表时间：
2021
影响因子：
5.7
通讯作者：
Cox SC
中科院分区：
文献类型：
--
作者：
Man K;Brunet MY;Louth S;Robinson TE;Fernandez-Rhodes M;Williams S;Federici AS;Davies OG;Hoey DA;Cox SC
细胞外囊泡(EVS)被认为是一种很有前途的纳米级骨再生疗法。到目前为止，电动汽车通常是从2D组织培养塑料上的细胞获得的，这是一种限制细胞生长的人工环境，不能复制原位生化或生物物理条件。本研究探讨了涂覆羟基磷灰石的3D打印钛支架对成骨细胞源性EVS治疗效果的促进作用。采用选择性激光熔凝的方法制备了不同孔径(500和1000µm)、形状(正方形和三角形)的Ti6Al4V钛支架。然后应用仿骨纳米针状羟基磷灰石(NnHA)涂层。从支架培养的成骨细胞中获取EVS超过2周，并用CD63-EL ISA测定囊泡浓度。通过检测碱性磷酸酶活性、胶原合成和钙沉积来评价EVS诱导的人骨髓基质细胞(HBMSCs)的成骨分化。与方形结构相比，三角形孔支架显著增加了成骨细胞的矿化(P≤0.001)。有趣的是，在这些较高渗透率的结构上(P≤0.001)，电动汽车的产量也得到了显著的提高，特别是较大的孔结构(1000µm)的电动汽车产量(2.2%)。此外，从三角形孔支架中分离的成骨细胞来源的EV显著增加了hBMSCs的矿化，与方孔支架获得的EV(1.7倍)和2D培养的EV(2.2倍)相比(P≤0.001)。与未涂覆的支架相比，涂覆纳米羟基磷灰石显著提高了成骨细胞矿化(>；2.6倍)和电动汽车产量(4.5倍)(P≤0.001)。综上所述，这些发现证明了利用仿骨培养平台来提高促再生EVS的生产作为骨修复的去细胞工具的潜力。
Extracellular Vesicles (EVs) are considered promising nanoscale therapeutics for bone regeneration. To date, EVs are typically procured from cells on 2D tissue culture plastic, an artificial environment that limits cell growth and does not replicate in situ biochemical or biophysical conditions. This study investigated the potential of 3D printed titanium scaffolds coated with hydroxyapatite to promote the therapeutic efficacy of osteoblast-derived EVs. Ti6Al4V titanium scaffolds with different pore sizes (500 and 1000 µm) and shapes (square and triangle) were fabricated by selective laser melting. A bone-mimetic nano-needle hydroxyapatite (nnHA) coating was then applied. EVs were procured from scaffold-cultured osteoblasts over 2 weeks and vesicle concentration was determined using the CD63 ELISA. Osteogenic differentiation of human bone marrow stromal cells (hBMSCs) following treatment with primed EVs was evaluated by assessing alkaline phosphatase activity, collagen production and calcium deposition. Triangle pore scaffolds significantly increased osteoblast mineralisation (1.5-fold) when compared to square architectures (P ≤ 0.001). Interestingly, EV yield was also significantly enhanced on these higher permeability structures (P ≤ 0.001), in particular (2.2-fold) for the larger pore structures (1000 µm). Furthermore osteoblast-derived EVs isolated from triangular pore scaffolds significantly increased hBMSCs mineralisation when compared to EVs acquired from square pore scaffolds (1.7-fold) and 2D culture (2.2-fold) (P ≤ 0.001). Coating with nnHA significantly improved osteoblast mineralisation (>2.6-fold) and EV production (4.5-fold) when compared to uncoated scaffolds (P ≤ 0.001). Together, these findings demonstrate the potential of harnessing bone-mimetic culture platforms to enhance the production of pro-regenerative EVs as an acellular tool for bone repair.
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影响因子：
10
作者：
Eichholz, Kian F.;Von Euw, Stanislas;Hoey, David A.
通讯作者：
Hoey, David A.
影响因子：
8.2
作者：
Damiati L;Eales MG;Nobbs AH;Su B;Tsimbouri PM;Salmeron-Sanchez M;Dalby MJ
通讯作者：
Dalby MJ
影响因子：
2.4
作者：
Guilak, Farshid;Butler, David L.;Goldstein, Steven A.;Baaijens, Frank P. T.
通讯作者：
Baaijens, Frank P. T.
影响因子：
2.7
作者：
Baraniak PR;McDevitt TC
通讯作者：
McDevitt TC
源自人间充质干细胞的治疗微泡的有效可扩展产生。
影响因子：
4.6
作者：
Cha JM;Shin EK;Sung JH;Moon GJ;Kim EH;Cho YH;Park HD;Bae H;Kim J;Bang OY
通讯作者：
Bang OY