DNA hydrogels for bone regeneration

炎症和肿瘤性疾病引起的骨丢失的临床治疗需要开发定制的工程材料，这种材料可以可靠地概括实现骨再生的基本生物过程。这些过程包括成骨细胞的募集和分化，以及提供分子模板来促进羟基磷灰石(HA)的引导矿化。目前的生物材料是有限的，因为它们的分子性质只调节这些过程的一个子集。纳米工程DNA具有内在的三维组装能力，最近被提出作为模拟细胞外基质(ECM)的支架。这些基于DNA的材料已被用于引导矿化和软组织再生，但在骨再生方面的应用尚未被开发。目的：优化基于DNA的材料、DNA水凝胶的组成，以促进大鼠颅骨全层骨缺损的修复。假设：更坚硬的DNA水凝胶和DNA水凝胶具有促进矿化和/或细胞粘附肽的功能，将上调骨分化，促进矿化导致骨修复。合作小组：多伦多大学(Carneiro)的团队将设计和合成不同组成的DNA水凝胶。巴西Unesp(Okamoto)的研究小组将在大鼠颅骨模型上测试DNA水凝胶。动物模型的结果将以迭代的方式为DNA水凝胶的优化提供信息，从而为开发具有良好的骨再生性能的生物材料提供信息。意义：基于DNA的骨修复生物材料的开发将带来新的突破，将提高加拿大人的生活质量，降低医疗成本，并将推动创造新的产业和就业机会。这项工作将为骨再生提供新的机制见解和潜在的创新疗法。

Clinical management of bone loss due to inflammatory and neoplastic diseases requires the development of custom-engineered materials that can reliably recapitulate the fundamental biological processes that enable bone regeneration. These processes involve osteogenic cell recruitment and differentiation, and the provision of molecular templates that promote guided mineralization of hydroxyapatite (HA). Current biomaterials are limited because their molecular properties mediate only a subset of these processes. Nanoengineered DNA have an intrinsic capacity for 3D assembly and have recently been proposed as extracellular matrix (ECM)-mimetic scaffolds. These DNA-based materials have been used for guided mineralization and soft tissue regeneration, but applications in bone regeneration have not been explored.Objective: To optimize DNA-based material, DNA hydrogel, composition to promote full bone defect repair in a rat calvaria model.Hypothesis: Stiffer DNA hydrogels and DNA hydrogels functionalized with mineralization-promoting and/or cell adhesion peptides, will upregulate osteodifferentiation and promote mineralization leading to bone repair.Collaborative team: The team at University of Toronto (Carneiro) will design and synthesize DNA hydrogels with varying composition. The team at UNESP in Brazil (Okamoto) will test the DNA hydrogels in rat calvaria bone models. Animal model results will inform the optimization of the dna hydrogels in an iterative manner, thus informing the development of biomaterials with promising bone regeneration properties. Significance: Development of DNA-based biomaterials for bone repair will lead to new breakthroughs that will improve the quality of life and lower healthcare costs for Canadians, as well as will fuel the creation of new industry and jobs. This work will provide new mechanistic insights and potential innovative therapies for bone regeneration.