Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization

Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization
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DOI:
10.1016/s0168-3659(02)00181-5
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发表时间:
2002-09-18
影响因子:
10.8
通讯作者:
Anseth, KS
Anseth, KS
中科院分区:
医学1区
文献类型:
--
作者:
Burdick, JA;Mason, MN;Anseth, KS

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研究了具有不同质量损失特征的可降解聚乙二醇(PEG)水凝胶,以评估其作为骨组织工程中骨诱导生长因子递送载体的适用性。蛋白质的释放容易通过结构(即,大分子单体浓度)和化学(即,可降解单元的数目)。体外研究表明,与用标准培养基培养的细胞相比,在骨诱导生长因子存在下培养的成骨细胞的总蛋白水平、碱性磷酸酶和矿化增加。当从25重量%水凝胶递送生长因子时,在培养3周后观察到碱性磷酸酶和矿化的显著增加超过以推注方式递送生长因子。此外,当生长因子从水凝胶中释放时,骨钙素和I型胶原的基因表达水平在早期时间点较高。这些结果表明,生长因子在光包裹后仍然保持活性,生长因子的持续递送改变成骨细胞分化的各种标志物,并且这些网络可以用作骨组织工程中生长因子的递送载体。最后,异位骨形成存在于皮下大鼠组织植入后的水凝胶网络加载骨诱导生长因子。(C)2002 Elsevier Science B.V.保留所有权利。
Degradable poly(ethylene glycol) (PEG) hydrogels with varying mass loss profiles were investigated to assess their applicability as delivery vehicles for osteoinductive growth factors in bone tissue engineering. Protein release is readily controlled by changes in both the structure (i.e., macromer concentration) and chemistry (i.e., number of degradable units) of the starting macromer. In vitro studies indicate an increase in total protein levels, alkaline phosphatase, and mineralization by osteoblasts cultured in the presence of osteoinductive growth factors compared to cells cultured with standard media. When growth factors are delivered from a 25 wt% hydrogel, a significant increase in both alkaline phosphatase and mineralization was seen after 3 weeks of culture over growth factor delivery in a bolus fashion. Additionally, gene expression levels of both osteocalcin and type I collagen were higher at early timepoints when growth factors were released from hydrogels. These results indicate that growth factors remain active after photoencapsulation, that the sustained delivery of growth factors alters various markers of osteoblastic differentiation, and that these networks could be useful as delivery vehicles for growth factors in bone tissue engineering. Finally, ectopic bone formation was present in subcutaneous rat tissue after implantation of hydrogel networks loaded with osteoinductive growth factors. (C) 2002 Elsevier Science B.V. All rights reserved.