Growth factors produced by bone marrow stromal cells on nanoroughened titanium-aluminum-vanadium surfaces program distal MSCs into osteoblasts via BMP2 signaling.

Growth factors produced by bone marrow stromal cells on nanoroughened titanium-aluminum-vanadium surfaces program distal MSCs into osteoblasts via BMP2 signaling.
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DOI:
10.1002/jor.24869
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发表时间:
2021-09
期刊:
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子:
--
通讯作者:
Boyan BD
Boyan BD
中科院分区:
其他
文献类型:
--
作者:
Berger MB;Bosh KB;Jacobs TW;Joshua Cohen D;Schwartz Z;Boyan BD

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仍然需要开发能够提高骨整合率的植入物、表面和材料。虽然骨合成代谢剂,如骨形态发生蛋白(BMP),可以为骨形成提供信号,但适当设计的植入物也可以产生先天细胞反应,从而减少或消除使用其他药物来刺激骨形成的需要。研究表明,模拟破骨细胞吸收坑物理特性的钛植入物表面通过改变细胞形态、转录组和局部因子产生来调节骨髓基质细胞(MSCs)的细胞反应,从而增加其向成骨细胞(OBs)的分化,而无需在组织培养聚苯乙烯(TCPS)上向MSCs分化所需的成骨培养基补充。本研究的目的是确定细胞在体外与仿生植入物表面接触时如何调节这些表面周围的微环境。使用了两种不同的方法。首先,通过用Ti6Al4V仿生表面培养的MSC培养基处理在TCPS上生长的人MSC,评估单向信号。在第二组研究中,通过共培养在网状植入物上生长的间充质干细胞来评估双向信号,网状植入物被放置在培养孔中,其中间充质干细胞在仿生Ti6Al4V基质上生长。结果表明,仿生Ti6Al4V表面特性诱导MSCs在培养后7天内产生因子,这些因子通过内源性BMP2以旁分泌信号方式作用刺激未接触表面的MSCs表现出成骨细胞表型。
There remains the need to develop implants, surfaces, and materials that can increase the rate of osseointegration. While osteoanabolic agents, like bone morphogenetic protein (BMP), can provide signaling for osteogenesis, the appropriate design of implants can also produce an innate cellular response that may reduce or eliminate the need to use additional agents to stimulate bone formation. Studies show that titanium implant surfaces that mimic the physical properties of osteoclast resorption pits regulate cellular responses of bone marrow stromal cells (MSCs) by altering cell morphology, transcriptomes, and local factor production to increase their differentiation into osteoblasts (OBs) without osteogenic media supplements required for differentiation of MSCs on tissue culture polystyrene (TCPS). The goal of this research was to determine how cells in contact with biomimetic implant surfaces regulate the micro-environment around these surfaces in vitro. Two different approaches were used. First, unidirectional signaling was assessed by treating human MSCs grown on TCPS with conditioned media from MSC cultures grown on Ti6Al4V biomimetic surfaces. In the second set of studies, bidirectional signaling was assessed by co-culturing MSCs grown on mesh inserts that were placed into culture wells in which MSCs were grown on the biomimetic Ti6Al4V substrates. The results show that biomimetic Ti6Al4V surface properties induce MSCs to produce factors within 7 days of culture that stimulate MSCs not in contact with the surface to exhibit an osteoblast phenotype via endogenous BMP2 acting in a paracrine signaling manner.
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