Tunable delivery of bioactive peptides from hydroxyapatite biomaterials and allograft bone using variable-length polyglutamate domains.
Tunable delivery of bioactive peptides from hydroxyapatite biomaterials and allograft bone using variable-length polyglutamate domains.
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使用可变的长度聚谷氨酸结构域，可调节从羟基磷灰石生物材料和同种异体移植骨中递送生物活性肽。
DOI：
10.1002/jbm.a.34766
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发表时间：
2014-04
影响因子：
4.9
通讯作者：
Bellis, Susan L.
中科院分区：
文献类型：
--
作者：
Culpepper, Bonnie K.;Webb, William M.;Bonvallet, Paul P.;Bellis, Susan L.
羟基磷灰石（HA）生物材料和同种异体骨是自体移植物的常见替代品，但这些材料缺乏自体骨的强骨诱导潜力。先前的研究已经确定，选择性结合HA的聚谷氨酸结构域可以被工程化到生物活性肽上，作为将骨诱导信号偶联到HA和同种异体移植物上的机制。在目前的研究中，我们采用了聚谷氨酸的方法，通过操纵HA结合结构域中谷氨酸的数量来定制模型胶原衍生肽DGEA的递送。具体地，DGEA用二谷氨酸盐（E2-DGEA）、四谷氨酸盐（E4-DGEA）或七谷氨酸盐（E7-DGEA）修饰，并且发现初始肽与HA和同种异体移植物的结合随着谷氨酸盐数目的增加而显著增强。我们还确定了在5天的时间间隔内，随着谷氨酸残基的数量减少，聚谷氨酸-DGEA从底物中的释放速率成比例地增加。此外，我们通过产生E2-DGEA、E4-DGEA和E7-DGEA的混合物来调节肽释放速率，并观察到混合物的释放动力学不同于每种相应肽的纯溶液。这些集体的结果表明，可变长度的聚谷氨酸结构域提供了一个有效的机制，控制交付的骨再生肽HA含骨移植材料。
Hydroxyapatite (HA) biomaterials and allograft bone are common alternatives to autogenous grafts, however these materials lack the strong osteoinductive potential of autologous bone. Previous studies have established that polyglutamate domains, which bind selectively to HA, can be engineered onto bioactive peptides as a mechanism for coupling osteoinductive signals onto HA and allograft. In the current investigation, we adapted the polyglutamate approach to tailor delivery of a model collagen-derived peptide, DGEA, by manipulating the number of glutamates in the HA binding domain. Specifically, DGEA was modified with diglutamate (E2-DGEA), tetraglutamate (E4-DGEA) or heptaglutamate (E7-DGEA), and it was found that initial peptide binding to HA and allograft was significantly enhanced as the number of glutamates increased. We also determined that the rate of release of polyglutamate-DGEA from substrates over a 5-day interval increased proportionally as the number of glutamate residues was decreased. Additionally, we tuned the peptide release rate by creating mixtures of E2-DGEA, E4-DGEA and E7-DGEA, and observed that release kinetics of the mixtures were distinct from pure solutions of each respective peptide. These collective results suggest that variable length polyglutamate domains provide an effective mechanism for controlled delivery of osteoregenerative peptides on HA-containing bone graft materials.
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影响因子：
9.7
作者：
Lee, Jae Sam;Lee, Jae Sung;Murphy, William L.
通讯作者：
Murphy, William L.
影响因子：
14
作者：
Culpepper, Bonnie K.;Bonvallet, Paul P.;Reddy, Michael S.;Ponnazhagan, Selvarangan;Bellis, Susan L.
通讯作者：
Bellis, Susan L.
影响因子：
7.3
作者：
Borcard, Francoise;Staedler, Davide;Gerber-Lemaire, Sandrine
通讯作者：
Gerber-Lemaire, Sandrine
影响因子：
14
作者：
Sawyer, AA;Weeks, DM;Bellis, SL
通讯作者：
Bellis, SL
影响因子：
4
作者：
Lin, Genyao;Cosimbescu, Lelia;Tarasevich, Barbara J.
通讯作者：
Tarasevich, Barbara J.