Calcium Phosphate Mineralization of Hydrogels, their Microstructure and Mechanical Behavior

这笔赠款支持促进制造过程知识的研究，促进科学进步和国民健康。在美国，每年有超过50万的患者需要修复骨缺损，需要先进的骨替代和再生材料制造方法。一种很有前途的方法是利用水凝胶材料的磷酸钙矿化。磷酸钙是骨的矿物成分，矿化水凝胶作为骨缺损的替代材料，具有良好的仿生性能和机械强度。尽管对成矿作用的认识有了长足的进步，但对这些杂化材料的成矿途径、微观结构和力学响应之间的关系的了解仍然很少，这阻碍了制造科学的进步。这笔赠款支持基础研究，为水凝胶矿化过程的开发提供必要的知识，使其能够控制其结构-机械性能关系。所获得的知识将适用于通过非生物矿化进行骨替代的生物材料的先进制造。此外，所获得的洞察力也将与控制生物矿化途径相关，从而对基于组织工程的骨再生具有重要意义。因此，这项研究的结果将使美国社会受益。这项研究涉及多个学科，包括材料科学与工程、化学和力学，将有助于美国劳动力的发展。多学科研究将有助于扩大未被充分代表的群体参与研究并对工程教育产生积极影响。本研究的总体目标是理解、量化和建模在无定形碳酸钙(ACC)前驱体存在下的磷酸钙的矿化途径、矿化水凝胶的微观结构及其力学响应之间的关系。这笔赠款支持的研究将阐明：i)水凝胶中ACC的存在如何影响矿化途径；ii)聚合物性质(电荷密度、化学交联度与物理缠结和自组装能力)、矿化机理和微观结构之间的关系；iii)溶液化学对矿化速率的影响；以及iv)矿化水凝胶的微观结构和流变学之间的关系。这项工作的发现将被用来开发一个概念性框架，以预测水凝胶通过磷酸钙矿化作为溶液组成和水凝胶性质的函数的强化机制。实验旨在检验特定的潜在机制，并检验提出的假设，这些假设涉及矿化过程中液态前体的初始形成、诱导的聚合物-矿物相互作用强度以及水凝胶中的纳米颗粒聚集。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This grant supports research that advances knowledge of the manufacturing process promoting both the progress of science and national health. Every year, over half a million patients need bone defect repairs in the U.S. and advanced manufacturing methods of materials for bone replacement and regeneration are needed. A promising method is the use of calcium phosphate mineralization of hydrogel materials. Calcium phosphate is the mineral component of bone and mineralized hydrogels could yield both suitable biomimetic properties and mechanical strength as a bone defect replacement material. Despite the significant advance in understanding mineralization, knowledge of the relation between the mineralization pathway, the microstructure and the mechanical response of these hybrid materials is still lacking, which hinders advances in manufacturing science. This grant supports fundamental research to provide that needed knowledge for the development of mineralization processes of hydrogels that allow control of their structure-mechanical property relation. The gained knowledge will be applicable to advance manufacturing of biomaterials via abiotic mineralization for bone replacement. Furthermore, the gained insight will be also relevant to control biotic mineralization pathways, and hence, for bone regeneration based on tissue engineering. Therefore, results from this research will benefit the U.S. society. This research involves several disciplines including materials science and engineering, chemistry, and mechanics and will contribute to the development of workforce in the U.S. The multi-disciplinary research will help broaden participation of underrepresented groups in research and positively impact engineering education.The overall objective of this research is to comprehend, quantify and model the relation between mineralization pathways of calcium phosphate in the presence of amorphous calcium carbonate (ACC) precursors, the microstructure of the mineralized hydrogel and its mechanical response. This grant supports the research that will elucidate i) how the mineralization pathway is affected by the presence of ACC in the hydrogels, ii) the relation between polymer properties (charge density, chemical crosslinks vs. physical entanglements and self-assembly capability), mineralization mechanisms and microstructure, iii) the effect of the solution chemistry on the mineralization rate, and iv) the relation between microstructure and rheology of mineralized hydrogels. The findings of this work will be used to develop a conceptual framework to predict strengthening mechanisms of hydrogels via calcium phosphate mineralization as a function of solution composition and hydrogel properties. Experiments are designed to examine specific underlying mechanisms and test the posed hypotheses concerning issues such as the initial formation of a liquid-phase precursor en route to mineralization, the induced polymer-mineral interaction strength, and the nanoparticle aggregation in the hydrogel.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.