Bone regeneration with low dose BMP-2 amplified by biomimetic supramolecular nanofibers within collagen scaffolds.
Bone regeneration with low dose BMP-2 amplified by biomimetic supramolecular nanofibers within collagen scaffolds.
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DOI：
10.1016/j.biomaterials.2012.10.005
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发表时间：
2013-01
期刊：
影响因子：
14
通讯作者：
Stupp, Samuel I.
中科院分区：
文献类型：
--
作者：
Lee, Sungsoo S.;Huang, Brian J.;Kaltz, Stuart R.;Sur, Shantanu;Newcomb, Christina J.;Stock, Stuart R.;Shah, Ramille N.;Stupp, Samuel I.
关键词：
骨形态发生蛋白-2（BMP-2）是一种有效的骨诱导细胞因子，在骨再生和修复过程中起着关键作用。在细胞外环境中，硫酸多糖共价锚定到糖蛋白如多配体蛋白聚糖，也非共价锚定到纤连蛋白纤维已被证明通过肝素结合结构域结合BMP-2，并调节其生物活性。我们在这里报告了一种合成的仿生策略，通过使用肽两亲物纳米纤维结合肝素来模拟生物BMP-2信号。整合了多配体蛋白聚糖和纤连蛋白的生物学作用的超分子纳米纤维被允许通过简单地渗透肽两亲物、硫酸乙酰肝素和BMP-2的稀溶液在可吸收胶原支架的孔内形成凝胶网络。混合生物材料在大鼠临界尺寸股骨缺损模型中使用BMP-2量显著增强骨再生，该BMP-2量比该动物模型中愈合所需的量低一个数量级。使用显微计算机断层扫描，我们还表明，相对于基于胶原蛋白和BMP-2的临床使用类型的传统支架，混合支架在差距内桥接更有效。组织学评价还显示，当使用仿生超分子系统递送低剂量的BMP-2时，在新的骨化组织中存在更成熟的骨。这些结果表明，分子设计的材料，模拟细胞外环境的功能，可以放大生长因子的再生能力。
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role during bone regeneration and repair. In the extracellular environment, sulfated polysaccharides anchored covalently to glycoproteins such as syndecan and also non-covalently to fibronectin fibers have been shown to bind BMP-2 through a heparin-binding domain and regulate its bioactivity. We report here on a synthetic biomimetic strategy that emulates biological BMP-2 signaling through the use of peptide amphiphile nanofibers designed to bind heparin. The supramolecular nanofibers, which integrate the biological role of syndecan and fibronectin, were allowed to form gel networks within the pores of an absorbable collagen scaffold by simply infiltrating dilute solutions of the peptide amphiphile, heparan sulfate, and BMP-2. The hybrid biomaterial enhanced significantly bone regeneration in a rat critical-size femoral defect model using BMP-2 amounts that are one order of magnitude lower than required for healing in this animal model. Using micro-computed tomography, we also showed that the hybrid scaffold was more effective at bridging within the gap relative to a conventional scaffold of the type used clinically based on collagen and BMP-2. Histological evaluation also revealed the presence of more mature bone in the new ossified tissue when the low dose of BMP-2 was delivered using the biomimetic supramolecular system. These results demonstrate how molecularly designed materials that mimic features of the extracellular environment can amplify the regenerative capacity of growth factors.
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影响因子：
3.3
作者：
Kuo WJ;Digman MA;Lander AD
通讯作者：
Lander AD
影响因子：
14
作者：
Ghanaati, Shahram;Webber, Matthew J.;Unger, Ronald E.;Orth, Carina;Hulvat, James F.;Kiehna, Sarah E.;Barbeck, Mike;Rasic, Angela;Stupp, Samuel I.;Kirkpatrick, C. James
通讯作者：
Kirkpatrick, C. James
影响因子：
6.2
作者：
Barnes, GL;Kostenuik, PJ;Einhorn, TA
通讯作者：
Einhorn, TA
DOI：
10.1073/pnas.0737381100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Lutolf, MP;Lauer-Fields, JL;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
29.4
作者：
Jongpoiboonkit, Leenaporn;Franklin-Ford, Travelle;Murphy, William L.
通讯作者：
Murphy, William L.