Synergistic Effects of SDF-1α and BMP-2 Delivery from Proteolytically Degradable Hyaluronic Acid Hydrogels for Bone Repair.
Synergistic Effects of SDF-1α and BMP-2 Delivery from Proteolytically Degradable Hyaluronic Acid Hydrogels for Bone Repair.
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DOI：
10.1002/mabi.201500178
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发表时间：
2015-09
影响因子：
4.6
通讯作者：
Burdick JA
中科院分区：
文献类型：
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作者：
Holloway JL;Ma H;Rai R;Hankenson KD;Burdick JA
为了实现足够的骨修复，骨形态发生蛋白-2（BMP-2）通常以大的非生理剂量递送，并且可能导致显著的不良副作用。为了减少骨形成所必需的BMP-2的量，我们递送了另一种分子，基质细胞衍生因子-1 α（SDF-1α），其与BMP-2组合参与干细胞募集。使用通过基质金属蛋白酶（MMP）降解的工程化透明质酸（HA）水凝胶来递送两种分子，并且释放由蛋白酶水平介导。使用临界尺寸的颅骨缺损模型来评估生物分子递送对骨形成的影响。与单独负载相同浓度的BMP-2或SDF-1α的水凝胶相比，SDF-1α和BMP-2水凝胶组合递送的治疗组显示出显著更高的骨形成，并且与浓度高一个数量级的BMP-2相当，这表明两种生物分子的组合递送协同改善了骨生成。
In order to achieve adequate bone repair, bone morphogenetic protein-2 (BMP-2) is typically delivered in large, non-physiological doses and can result in significant adverse side effects. To reduce the amount of BMP-2 necessary for bone formation, we delivered another molecule, stromal cell derived factor-1α (SDF-1α), which is involved in stem cell recruitment in combination with BMP-2. An engineered hyaluronic acid (HA) hydrogel that degrades via matrix metalloproteinases (MMPs) was used to deliver both molecules and release was mediated by protease level. A critical-sized calvarial defect model was used to assess biomolecule delivery on bone formation. The treatment group with combined SDF-1α and BMP-2 hydrogel delivery showed significantly higher bone formation when compared to hydrogels loaded with the same BMP-2 or SDF-1α concentration alone and was comparable to BMP-2 at an order of magnitude higher concentration, suggesting that the combined delivery of both biomolecules synergistically improves osteogenesis.