1 Department of Biomedical Engineering, Virginia Commonwealth University , Richmond, Virginia.
2 Department of Biomedical Engineering, Georgia Institute of Technology , Atlanta, Georgia .
Tissue Eng Part A. 2017 Oct;23(19-20):1132-1141. doi: 10.1089/ten.TEA.2017.0003. Epub 2017 May 19.
Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties.
Human MSCs were cultured on Ti substrates (smooth [PT], sandblasted acid-etched [SLA], hydrophilic-SLA [modSLA]), or tissue culture polystyrene (TCPS). After 7 days, inflammatory mRNAs were measured by polymerase chain reaction array. In addition, 7-day cultures were treated with exogenous BMP2 and osteogenic differentiation and production of local factors, proinflammatory interleukins, and anti-inflammatory interleukins assessed. Finally, osteogenic markers and interleukins were measured in MSCs cultured for 48 h on BMP2 dip-coated SLA and modSLA surfaces.
Expression of interleukins, chemokines, cytokines, and growth factors was affected by surface properties, particularly on modSLA. MSCs on Ti produced fewer resorptive and more osteogenic/anti-inflammatory factors than cells on TCPS. Addition of 100 ng/mL BMP2 not only increased differentiation but also increased proinflammatory and decreased anti-inflammatory/antiresorptive factors. Two hundred nanograms per milliliter BMP2 abolished osteogenesis and dramatically increased pro-osteoclastogenic factors. MSCs cultured on BMP2-dip-coated disks produced similar proinflammatory profiles with inhibited osteogenic differentiation and had increased apoptotic markers at the highest doses.
MSCs underwent osteogenesis and regulated inflammatory cytokines on microtextured Ti. Exogenous BMP2 inhibited MSC differentiation and stimulated a dose-dependent proinflammatory and apoptotic response. Use of BMP2 with microtextured metal implants may increase inflammation and possibly delay bone formation dependent on dose, suggesting that application of BMP2 clinically during implant insertion may need to be reevaluated.
微纹理钛（Ti）在没有外源性成骨因子的情况下诱导间充质干细胞（MSCs）的成骨分化；高能表面改性加速微粗糙 Ti 植入物的愈合。骨形态发生蛋白 2（BMP2）临床上用于改善种植体周围骨形成和骨整合，但可引起炎症和骨相关并发症。在这项研究中，我们确定了当在具有不同表面特性的 Ti 植入物上生长时，BMP2 是否改变了人 MSC 的分化、凋亡和炎症因子的产生。
将人 MSC 培养在 Ti 基底（光滑 [PT]、喷砂酸蚀 [SLA]、亲水-SLA [modSLA]）或组织培养聚苯乙烯（TCPS）上。7 天后，通过聚合酶链反应阵列测量炎症性 mRNA。此外，用外源性 BMP2 处理 7 天培养物，并评估成骨分化和局部因子、促炎细胞因子和抗炎细胞因子的产生。最后，在 BMP2 浸泡的 SLA 和 modSLA 表面上培养 MSC 48 小时后，测量成骨标志物和细胞因子。
细胞因子、趋化因子、细胞因子和生长因子的表达受表面特性的影响，尤其是在 modSLA 上。Ti 上的 MSC 比 TCPS 上的细胞产生更少的吸收性和更多的成骨/抗炎性因子。添加 100ng/ml BMP2 不仅增加了分化，还增加了促炎因子，减少了抗炎/抗吸收因子。200ng/ml BMP2 消除了成骨作用，并显著增加了促破骨细胞生成因子。在 BMP2 浸泡的磁盘上培养的 MSC 产生了相似的促炎谱，抑制了成骨分化，并在最高剂量下增加了凋亡标志物。
MSCs 在微纹理 Ti 上进行成骨和调节炎症细胞因子。外源性 BMP2 抑制 MSC 分化，并刺激剂量依赖性的促炎和凋亡反应。在微纹理金属植入物中使用 BMP2 可能会增加炎症，并可能延迟骨形成，这取决于剂量，这表明在植入物插入过程中临床应用 BMP2 可能需要重新评估。
