Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences , ul. Sienkiewicza 112, 90-363 Lodz, Poland.
Biomacromolecules. 2017 Oct 9;18(10):3418-3431. doi: 10.1021/acs.biomac.7b01071. Epub 2017 Sep 13.
We present biocompatible hydrogel systems suitable for biomineralization processes based on hyperbranched polyglycidol cross-linked with acrylamide copolymer bearing carbonyl-coordinated boronic acid. At neutral pH, diol functional groups of HbPGL react with boronic acid of polyacrylamide to generate 3D network in water by the formation of boronic ester cross-links. The dynamic associative/dissociative characteristics of the cross-links makes the network reversible. The presented hydrogels display self-healing properties and are injectable, facilitating gap filing of bone tissue. The H HR MAS DOSY NMR studies reveal that acrylamide copolymer plays the role of the network framework, whereas HbPGL macromolecules, due to their compact structure, move between reactive sites of the copolymer. The influence of the copolymer macromolecules entanglements and overall polymer concentrations on macromolecules mobility and stress relaxation processes is investigated. The process of hydrogel biomineralization results from hydrolysis of 1-naphthyl phosphate calcium salt catalyzed by encapsulation in hydrogel alkaline phosphatase. The environment of the hydrogel is entirely neutral toward the enzyme. However, the activity of alkaline phosphatase encapsulated within the hydrogel structure is diffusion-limited. In this article, based on the detailed characteristics of three model hydrogel systems, we demonstrate the influence of the hydrogel permeability on the encapsulated enzyme activity and calcium phosphate formation rate. The H HR MAS DOSY NMR is used to monitor diffusion low-molecular weight compound within hydrogels, whereas P HR MAS NMR facilitates monitoring of the progress of biomineralization in situ within hydrogels. The results show a direct correlation between low molecular diffusivity in hydrogels and network dynamics. We demonstrate that the morphology of in situ-generated calcium phosphate within three model HbPGL/poly(AM-ran-APBA) hydrogels of different low molecular permeability varies substantially from sparsely deployed large, well-defined crystals to an even distribution within the polymers polycrystalline continuous network.
我们提出了适用于基于超支化聚缩水甘油与带有羰基配位硼酸的丙烯酰胺共聚物交联的生物矿化过程的生物相容性水凝胶系统。在中性 pH 下，HbPGL 的二醇官能团与聚丙烯酰胺中的硼酸反应，通过形成硼酸酯交联在水中生成 3D 网络。交联的动态缔合/解缔合特性使网络具有可逆性。所提出的水凝胶具有自修复性能，并且可注射，有利于骨组织的间隙填充。HR MAS DOSY NMR 研究表明，丙烯酰胺共聚物起着网络框架的作用，而 HbPGL 大分子由于其紧凑的结构，在共聚物的反应位点之间移动。研究了共聚物大分子缠结和总聚合物浓度对大分子流动性和应力松弛过程的影响。水凝胶的生物矿化过程是由 1-萘基磷酸钙盐在水凝胶中的碱性磷酸酶催化下水解产生的。水凝胶的环境对酶完全呈中性。然而，包封在水凝胶结构中的碱性磷酸酶的活性受到扩散限制。在本文中，基于三个模型水凝胶系统的详细特征，我们证明了水凝胶渗透性对包封酶活性和磷酸钙形成速率的影响。H HR MAS DOSY NMR 用于监测水凝胶中低分子量化合物的扩散，而 P HR MAS NMR 有助于监测水凝胶中生物矿化的原位进展。结果表明，水凝胶中的低分子扩散率与网络动力学之间存在直接相关性。我们证明了三种不同低分子渗透性的 HbPGL/聚（AM-ran-APBA）水凝胶中原位生成的磷酸钙的形态从稀疏分布的大、定义良好的晶体到聚合物多晶连续网络内的均匀分布有很大的不同。
