The Effects of Stably Tethered BMP-2 on MC3T3-E1 Preosteoblasts Encapsulated in a PEG Hydrogel,Biomacromolecules

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The Effects of Stably Tethered BMP-2 on MC3T3-E1 Preosteoblasts Encapsulated in a PEG Hydrogel
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-02-08 , DOI: 10.1021/acs.biomac.0c01085
Sarah A Schoonraad ₁ , Michael L Trombold ₂ , Stephanie J Bryant _{1,

2,

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Affiliation

Bone morphogenetic protein-2 (BMP-2) is a clinically used osteoinductive growth factor. With a short half-life and side effects, alternative delivery approaches are needed. This work examines thiolation of BMP-2 for chemical attachment to a poly(ethylene glycol) hydrogel using thiol-norbornene click chemistry. BMP-2 retained bioactivity post-thiolation and was successfully tethered into the hydrogel. To assess tethered BMP-2 on osteogenesis, MC3T3-E1 preosteoblasts were encapsulated in matrix metalloproteinase (MMP)-sensitive hydrogels containing RGD and either no BMP-2, soluble BMP-2 (5 nM), or tethered BMP-2 (40–200 nM) and cultured in a chemically defined medium containing dexamethasone for 7 days. The hydrogel culture supported MC3T3-E1 osteogenesis regardless of BMP-2 presentation, but tethered BMP-2 augmented the osteogenic response, leading to significant increases in osteomarkers, Bglap and Ibsp. The ratio, Ibsp-to-Dmp1, highlighted differences in the extent of differentiation, revealing that without BMP-2, MC3T3-E1 cells showed a higher expression of Dmp1 (low ratio), but an equivalent expression with tethered BMP-2 and more abundant bone sialoprotein. In addition, this work identified that dexamethasone contributed to Ibsp expression but not Bglap or Dmp1 and confirmed that tethered BMP-2 induced the BMP canonical signaling pathway. This work presents an effective method for the modification and incorporation of BMP-2 into hydrogels to enhance osteogenesis.

中文翻译：

稳定束缚 BMP-2 对 PEG 水凝胶包裹的 MC3T3-E1 前成骨细胞的影响

骨形态发生蛋白 2 (BMP-2) 是临床上使用的骨诱导生长因子。由于半衰期短且有副作用，因此需要替代递送方法。这项工作使用硫醇-降冰片烯点击化学检查了 BMP-2 的硫醇化以化学附着到聚（乙二醇）水凝胶上。BMP-2 在硫醇化后保留了生物活性，并成功地束缚在水凝胶中。为了评估束缚 BMP-2 对成骨的影响，将 MC3T3-E1 前成骨细胞包裹在对基质金属蛋白酶 (MMP) 敏感的水凝胶中，该水凝胶含有 RGD，不含 BMP-2、可溶性 BMP-2 (5 nM) 或束缚 BMP-2 (40– 200 nM）并在含有地塞米松的化学成分确定的培养基中培养 7 天。无论 BMP-2 呈递如何，水凝胶培养物都支持 MC3T3-E1 成骨，但束缚的 BMP-2 增强了成骨反应，Bglap和Ibsp。Ibsp与Dmp 1的比率突出了分化程度的差异，表明在没有 BMP-2 的情况下，MC3T3-E1 细胞表现出更高的Dmp 1 表达（低比率），但与束缚 BMP-2 的表达相当和更丰富的骨唾液蛋白。此外，这项工作确定地塞米松对Ibsp表达有贡献，但对Bglap或Dmp 1 没有影响，并证实栓系 BMP-2 诱导了 BMP 经典信号通路。这项工作提出了一种将 BMP-2 修饰和掺入水凝胶以增强成骨的有效方法。

更新日期：2021-03-08

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