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首页> 外文期刊>Advanced Functional Materials >Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering
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Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering

机译：稳定的细胞外基质模拟水凝胶的智能设计：合成，表征，以及组织工程的体外和体内评估。

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摘要

The simplicity and versatility of hydrazone crosslinking has made it a strategy of choice for the conjugation of bioactive molecules. However, the labile nature of hydrazone linkages and reversibility of this coupling reaction restricts its full potential. Based on the fundamental understanding of hydrazone stability, this problem is circumvented by resonance-stabilization of a developing N~2 positive charge in a hydrazone bond. A novel chemistry is presented to develop a resilient hydrazone bond that is stable and non-reversible under physiological conditions. A carbodihydrazide (CDH) type hydrazide derivative of the biomolecule forms intrinsically stabilized hydrazone-linkages that are nearly 15-fold more stable at phi 5 than conventional hydrazone. This chemoselective coupling reaction is catalyst-free, instantaneous, and virtually non-cleavable under physiological conditions, therefore can serve as a catalyst-free alternative to click chemistry. This novel crosslinking reaction is used to tailor a hyaluronan hydrogel, which delivered exceptional hydrolytic stability, mechanical properties, low swelling, and controlled enzymatic degradation. These desired characteristics are achieved without increasing the chemical crosslinking. The in vivo evaluation of this hydrogel revealed neo-bone with highly ordered collagen matrix mimicking natural bone regeneration. The proximity ligation assay or PLA is used to detect blood vessels, which highlighted the quality of engineered tissue.
机译：crosslinking交联的简单性和多功能性使其成为结合生物活性分子的一种选择策略。但是，键的不稳定性质和该偶联反应的可逆性限制了其全部潜力。基于对stability稳定性的基本了解，可通过by键中正在形成的N〜2正电荷的共振稳定化来解决此问题。提出了一种新的化学方法以开发在生理条件下稳定且不可逆的弹性键。生物分子的碳二酰肼（CDH）型酰肼衍生物形成内在稳定的hydr键，其在phi 5处的稳定性比常规高了近15倍。该化学选择性偶联反应在生理条件下是无催化剂的，瞬时的，并且实际上是不可裂解的，因此可以作为点击化学的无催化剂替代品。这种新颖的交联反应可用于制备透明质酸水凝胶，该透明质酸水凝胶具有出色的水解稳定性，机械性能，低溶胀度和受控的酶促降解能力。在不增加化学交联的情况下实现了这些期望的特性。该水凝胶的体内评估显示，新骨具有模仿天然骨再生的高度有序的胶原蛋白基质。邻近结扎测定法或PLA用于检测血管，这突出了工程组织的质量。

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  • 来源
    《Advanced Functional Materials》 |2013年第10期|1273-1280|共8页
  • 作者

    Oommen P. Oommen; Shujiang Wang; Marta Kisiel; Marije Sloff; Jons Hilborn; Oommen P.Varghese;

  • 作者单位

    Department of Chemistry, SciLifeLab Uppsala Angstrom Laboratory, Uppsala University 75121 Uppsala, Sweden;

    Department of Chemistry, SciLifeLab Uppsala Angstrom Laboratory, Uppsala University 75121 Uppsala, Sweden;

    Department of Chemistry, SciLifeLab Uppsala Angstrom Laboratory, Uppsala University 75121 Uppsala, Sweden;

    Urology- Experimental Urology 267 Nijmegen Medical Centre Radboud University 6525 GA Nijmegen, The Netherlands;

    Department of Chemistry, SciLifeLab Uppsala Angstrom Laboratory, Uppsala University 75121 Uppsala, Sweden;

    Department of Chemistry, SciLifeLab Uppsala Angstrom Laboratory, Uppsala University 75121 Uppsala, Sweden;

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