Hendrikx Stephan, Kascholke Christian, Flath Tobias, Schumann Dirk, Gressenbuch Mathias, Schulze F Peter, Hacker Michael C, Schulz-Siegmund Michaela
Pharmaceutical Technology, Institute of Pharmacy, Leipzig University, Eilenburger Straße 15a, Leipzig 04317, Germany.
Department of Mechanical and Energy Engineering, Leipzig University of Applied Sciences, Karl-Liebknecht-Straße 134, Leipzig 04277, Germany.
Acta Biomater. 2016 Apr 15;35:318-29. doi: 10.1016/j.actbio.2016.02.038. Epub 2016 Feb 27.
We present a series of organic/inorganic hybrid sol-gel derived glasses, made from a tetraethoxysilane-derived silica sol (100% SiO2) and oligovalent organic crosslinkers functionalized with 3-isocyanatopropyltriethoxysilane. The material was susceptible to heat sterilization. The hybrids were processed into pore-interconnected scaffolds by an indirect rapid prototyping method, described here for the first time for sol-gel glass materials. A large panel of polyethylene oxide-derived 2- to 4-armed crosslinkers of molecular weights ranging between 170 and 8000Da were incorporated and their effect on scaffold mechanical properties was investigated. By multiple linear regression, 'organic content' and the 'content of ethylene oxide units in the hybrid' were identified as the main factors that determined compressive strength and modulus, respectively. In general, 3- and 4-armed crosslinkers performed better than linear molecules. Compression tests and cell culture experiments with osteoblast-like SaOS-2 cells showed that macroporous scaffolds can be produced with compressive strengths of up to 33±2MPa and with a pore structure that allows cells to grow deep into the scaffolds and form mineral deposits. Compressive moduli between 27±7MPa and 568±98MPa were obtained depending on the hybrid composition and problems associated with the inherent brittleness of sol-gel glass materials could be overcome. SaOS-2 cells showed cytocompatibility on hybrid glass scaffolds and mineral accumulation started as early as day 7. On day 14, we also found mineral accumulation on control hybrid glass scaffolds without cells, indicating a positive effect of the hybrid glass on mineral accumulation.
We produced a hybrid sol-gel glass material with significantly improved mechanical properties towards an application in bone regeneration and processed the material into macroporous scaffolds of controlled architecture by indirect rapid prototyping. We were able to produce macroporous materials of relevant porosity and pore size with compressive moduli, covering the range reported for cancellous bone while an even higher compressive strength was maintained. By multiple linear regression, we identified crosslinker parameters, namely organic content and the content of ethylene oxide units in the hybrids that predominantly determined the mechanics of the hybrid materials. The scaffolds proved to be cytocompatible and induced mineralization in SaOS-2 cells. This provides new insight on the critical parameters for the design of the organic components of covalent hybrid sol-gel glasses.
我们展示了一系列有机/无机杂化溶胶-凝胶衍生玻璃，由四乙氧基硅烷衍生的硅溶胶（100% SiO₂）和用3-异氰酸酯基丙基三乙氧基硅烷官能化的低价有机交联剂制成。该材料易于热灭菌。通过一种间接快速成型方法将这些杂化物加工成孔相互连通的支架，本文首次针对溶胶-凝胶玻璃材料描述了这种方法。引入了一大组分子量在170至8000Da之间的聚环氧乙烷衍生的2至4臂交联剂，并研究了它们对支架机械性能的影响。通过多元线性回归，“有机含量”和“杂化物中环氧乙烷单元的含量”分别被确定为决定抗压强度和模量的主要因素。一般来说，3臂和4臂交联剂的性能优于线性分子。对成骨样SaOS-2细胞进行的压缩试验和细胞培养实验表明，可以制备出抗压强度高达33±2MPa的大孔支架，其孔结构允许细胞深入支架生长并形成矿物质沉积。根据杂化组成，获得了27±7MPa至568±98MPa之间的压缩模量，并且可以克服与溶胶-凝胶玻璃材料固有脆性相关的问题。SaOS-2细胞在杂化玻璃支架上表现出细胞相容性，早在第7天就开始有矿物质积累。在第14天的时候，我们还在没有细胞的对照杂化玻璃支架上发现了矿物质积累，这表明杂化玻璃对矿物质积累有积极作用。
我们制备了一种杂化溶胶-凝胶玻璃材料，其在骨再生应用方面的机械性能有显著改善，并通过间接快速成型将该材料加工成具有可控结构的大孔支架。我们能够制备出具有相关孔隙率和孔径的大孔材料，其压缩模量涵盖了松质骨报道的范围，同时保持了更高的抗压强度。通过多元线性回归，我们确定了交联剂参数，即杂化物中的有机含量和环氧乙烷单元的含量，它们主要决定了杂化材料的力学性能。这些支架被证明具有细胞相容性，并能在SaOS-2细胞中诱导矿化。这为共价杂化溶胶-凝胶玻璃有机成分设计的关键参数提供了新的见解。
