Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation,Advanced Functional Materials

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Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2020-02-16 , DOI: 10.1002/adfm.201906205
Babatunde O. Okesola _{1,

2} , Shilei Ni ₃ , Burak Derkus _{1,

2,

4} , Carles C. Galeano _{1,

2} , Abshar Hasan _{5,

6} , Yuanhao Wu _{5,

6} , Jopeth Ramis ₆ , Lee Buttery ₆ , Jonathan I. Dawson ₇ , Matteo D'Este ₈ , Richard O. C. Oreffo ₇ , David Eglin ₈ , Hongchen Sun ₉ , Alvaro Mata _{1,

2,

5,

6,

10}

Affiliation

Institute of BioengineeringQueen Mary University of London London E1 4NS UK
School of Engineering and Materials ScienceQueen Mary University of London London E1 4NS UK
Department of Oral PathologySchool and Hospital of StomatologyJilin University Changchun 130000 China
Biomedical Engineering DepartmentFaculty of EngineeringEskisehir Osmangazi University 26040 Eskisehir Turkey
School of PharmacyUniversity of Nottingham Nottingham NG7 2RD UK
Biodiscovery InstituteUniversity of Nottingham Nottingham NG7 2RD UK
Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of Southampton Southampton SO16 6YD UK
AO Research Institute Davos Clavadelerstrasse 8 7270 Davos Platz Switzerland
Department of Oral and Maxillofacial PathologySchool and Hospital of StomatologyChina Medical University Shenyang 110000 China
Department of Chemical and Environmental EngineeringUniversity of Nottingham Nottingham NG7 2RD UK

Synthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu²⁺), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu²⁺ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.

中文翻译：

不含生长因子的多组分纳米复合水凝胶，可刺激骨形成

能够刺激和加速骨骼形成而无需添加外源细胞或生长因子的合成骨促进材料为世界人口老龄化提供了主要机会。一个由玻尿酸酪胺（HA-Tyr），生物活性肽两亲物（GHK-Cu ²⁺）和皂石（Lap）组成的联合组装系统报道了利用物理，机械和生物分子信号来工程化水凝胶，可以对其进行调节以增强骨骼的再生。多组分水凝胶的主要设计元素是自组装和酶介导的氧化偶联的整合，以优化结构和机械性能，并结合了骨和血管促进段以促进信号传导。光谱技术用于确认多组分水凝胶形成中正交共价和超分子相互作用的相互作用。此外，物理力学特征表明，与单组分水凝胶相比，多组分水凝胶显示出改善的抗压强度，应力松弛曲线，低溶胀率和延迟的酶促降解。在体外使用人间充质干细胞和人脐静脉内皮细胞验证了适用性，在体内使用兔上颌窦底重建模型验证了适用性。动物用HA-Tyr-HA-Tyr-GHK-Cu ²⁺水凝胶与包括市售Bio-Oss的对照相比，骨形成明显增强。

更新日期：2020-04-06

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