Qi Yipin, Ye Zhou, Fok Alex, Holmes Brian N, Espanol Monsterrat, Ginebra Maria-Pau, Aparicio Conrado
Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510000, China.
MDRCBB, Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, 16-212 Moos Tower, 515 Delaware St. SE, Minneapolis, MN, USA.
ACS Biomater Sci Eng. 2018 Aug 13;4(8):2758-2766. doi: 10.1021/acsbiomaterials.8b00512. Epub 2018 Jun 29.
Inspired by nature, poly(acrylic acid) (PAA) and other polyelectrolytes have been used as noncollagenous proteins (NCPs) surrogates for biomimetic intrafibrillar mineralization of collagen fibrils and thus, to model the ultrastructure of bone, to study the mechanism of bone mineralization and, more scarcely to fabricate scaffolds for hard tissue engineering. The objective of this study was to systematically investigate the effect of the molecular weight (MW) and the concentration of PAA on the rate and pattern of biomineralization of collagen matrices. Densified type I collagen films were mineralized in supersaturated PAA-stabilized amorphous calcium-phosphate (PAA-ACP) solutions containing increasing MW (2 kDa, 50 kDA, 450 kDa) and concentrations (10, 25, 50 mg/L) of PAA up to 7 days. The stability and physical properties of collagen-free PAA-ACP solutions were also investigated. In our system, lowering PAA MW and increasing PAA concentration resulted in solutions with increasing stability. Over stable PAA-ACP solutions that fully inhibited mineralization of the collagen matrices were achieved using PAA 2k-50. Conversely, unstable solutions were obtained using high PAA MW at low concentrations. Nucleation and growth of significant amount of extrafibrillar minerals on the collagen fibrils was obtained using these solutions. In a wide range of combined MW and concentration of PAA we obtained intrafibrillar mineralization of collagen with hydroxyapatite crystals aligned parallel to the collagen fibril as in natural tissues. Intrafibrillar mineralization was correlated with PAA-ACP stability and growth of the PAA-ACP particles in solution. Our results support using PAA to surrogate NCPs function as selective inhibitors or promoters of biological mineralization and provide parameters to manufacture new biomimetic scaffolds and constructs for bone and dentin tissue engineering.
受自然启发,聚丙烯酸(PAA)和其他聚电解质已被用作非胶原蛋白(NCPs)替代物,用于胶原蛋白原纤维的仿生纤维内矿化,从而模拟骨的超微结构,研究骨矿化机制,并且较少用于制造硬组织工程支架。本研究的目的是系统地研究PAA的分子量(MW)和浓度对胶原蛋白基质矿化速率和模式的影响。将致密化的I型胶原蛋白膜在含有不断增加的MW(2 kDa、50 kDa、450 kDa)和浓度(10、25、50 mg/L)的PAA的过饱和PAA稳定的无定形磷酸钙(PAA-ACP)溶液中矿化长达7天。还研究了不含胶原蛋白的PAA-ACP溶液的稳定性和物理性质。在我们的系统中,降低PAA MW并增加PAA浓度会导致溶液稳定性增加。使用PAA 2k-50可获得完全抑制胶原蛋白基质矿化的过稳定PAA-ACP溶液。相反,在低浓度下使用高PAA MW可获得不稳定溶液。使用这些溶液可在胶原蛋白原纤维上形成大量纤维外矿物质的成核和生长。在广泛的PAA MW和浓度组合范围内,我们获得了胶原蛋白的纤维内矿化,其中羟基磷灰石晶体与天然组织中一样平行于胶原蛋白原纤维排列。纤维内矿化与PAA-ACP稳定性和溶液中PAA-ACP颗粒的生长相关。我们的结果支持使用PAA替代NCPs发挥生物矿化的选择性抑制剂或促进剂的作用,并为制造用于骨和牙本质组织工程的新型仿生支架和构建体提供参数。