College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 305-764, South Korea.
Carbohydr Polym. 2015 Aug 1;126:130-40. doi: 10.1016/j.carbpol.2015.03.033. Epub 2015 Mar 23.
A biomineralized hydrogel system containing hyaluronic acid (HA) and poloxamer composed of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO-PPO-PEO) block copolymer was developed as a biomimetic thermo-responsive injectable hydrogel system for bone regeneration. Using HA and poloxamer macromers with polymerizable residues, organic/inorganic HA/poloxamer hydrogels with various compositions were prepared and subjected to a biomineralization process to mimic the bone extracellular matrix. An increase in HA content within the hydrogels enhanced intermolecular chelation with calcium ions, leading to an increase in nucleation and growth of calcium phosphate in the hydrogels. After the biomineralization procedure, a crystalline formation was observed within and on the surface of the hydrogel. All of the HA/poloxamer hydrogel samples exhibited relatively high water content of greater than 90% at 25 °C, and the water content was influenced by the HA/poloxamer composition, biomineralization, and temperature. In particular, the HA/poloxamer hydrogel was injectable through a syringe without demonstrating appreciable macroscopic fracture at room temperature, whereas it was more opaque and adopted a more rigid structure as the temperature increased because of the increasing hydrophobicity of poloxamer. The enzymatic degradation behavior of the hydrogels depended on the concentration of hyaluronidase, HA/poloxamer composition, and biomineralization. The release kinetics of model drugs from HA/poloxamer hydrogels was primarily dependent on the drug loading content, water content, biomineralization of the hydrogels, and ionic properties of the drug. These results indicate that biomineralized HA/poloxamer hydrogel is a promising candidate material for a biomimetic hydrogel system that promotes bone tissue repair and regeneration via local delivery of drugs.
一种基于透明质酸（HA）和泊洛沙姆的生物矿化水凝胶系统，由聚（氧化乙烯）/聚（氧化丙烯）/聚（氧化乙烯）（PEO-PPO-PEO）嵌段共聚物组成，作为一种仿生温敏型可注射水凝胶系统，用于骨再生。使用具有聚合性残基的 HA 和泊洛沙姆大分子单体，制备了具有各种组成的有机/无机 HA/泊洛沙姆水凝胶，并进行了生物矿化处理，以模拟骨细胞外基质。水凝胶中 HA 含量的增加增强了与钙离子的分子间螯合作用，导致水凝胶中磷酸钙的成核和生长增加。在生物矿化过程后，在水凝胶内部和表面观察到结晶形成。所有 HA/泊洛沙姆水凝胶样品在 25°C 时均表现出大于 90%的相对高含水量，并且水含量受 HA/泊洛沙姆组成、生物矿化和温度的影响。特别是，HA/泊洛沙姆水凝胶可通过注射器注射，而在室温下不会出现明显的宏观断裂，而随着温度的升高，由于泊洛沙姆疏水性的增加，水凝胶变得不透明且采用更刚性的结构。水凝胶的酶降解行为取决于透明质酸酶的浓度、HA/泊洛沙姆组成和生物矿化。模型药物从 HA/泊洛沙姆水凝胶中的释放动力学主要取决于药物载药量、水凝胶的含水量、生物矿化和药物的离子特性。这些结果表明，生物矿化的 HA/泊洛沙姆水凝胶是一种有前途的候选材料，可作为仿生水凝胶系统，通过局部递送药物促进骨组织修复和再生。
