Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Department of Orthopedics Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
ACS Appl Mater Interfaces. 2022 Mar 16;14(10):12038-12049. doi: 10.1021/acsami.1c23017. Epub 2022 Mar 3.
Bone tissue scaffolds with good bulk or surface osteoconductivity are always pursued by biomaterial scientists. In this paper, we design a tough and flexible amphoteric copolymer-based (AC) hydrogel with bioactive groups for bone regeneration. In detail, our hydrogels are copolymerized with -acyl glycinamide (NAGA), anionic acrylate alendronate (AcAln), and cationic (2-(acryloyloxy)ethyl) trimethyl ammonium chloride (DMAEA-Q) by free radical polymerization. There are three kinds of synergetic physical cross-links among our polyamphion hydrogels: (1) double hydrogen bonds between amide groups in NAGA to provide toughness, (2) hydrogen bonds between dual bisphosphite groups in AcAln, and (3) weak ionic pairs between the anionic bisphosphite groups and the cationic quaternary ammonium groups in DMAEA-Q to offer flexibility. The AC hydrogel shows osteoid-like viscoelasticity, which makes the AC hydrogel osteogenesis inductive. During the repairing process, the bioactive bisphosphite groups accelerate the calcium fixation to expedite the mineralization of the new-formed bone. At the same time, the surface charge property of AC hydrogels also prevents fibrous cyst formation, thus guaranteeing osseointegration. Our in vitro data strongly demonstrate that the AC hydrogel is an excellent matrix to induce osteogenesis of rat bone marrow mesenchymal stem cells. More importantly, the following in vivo experiments further prove that the AC hydrogel can reach satisfactory bone regeneration without encapsulation of seed cells or application of external simulating cues. These exciting results demonstrate that our AC hydrogel is a promising scaffold for bone regeneration. Our work can also inspire the constituent and structure design of biomaterial scaffolds for tissue regeneration.
具有良好的整体或表面成骨活性的骨组织支架一直是生物材料科学家所追求的。在本文中，我们设计了一种具有生物活性基团的坚韧且灵活的两性共聚体（AC）水凝胶，用于骨再生。具体来说，我们的水凝胶是通过自由基聚合与 -酰基甘氨酰胺（NAGA）、阴离子丙烯酰基阿仑膦酸盐（AcAln）和阳离子（2-（丙烯酰氧基）乙基）三甲基氯化铵（DMAEA-Q）共聚而成。我们的聚两性离子水凝胶中有三种协同的物理交联：（1）NAGA 中酰胺基团之间的氢键提供韧性，（2）AcAln 中双膦酸盐基团之间的氢键，以及（3）阴离子双膦酸盐基团和 DMAEA-Q 中的阳离子季铵基团之间的弱离子对提供灵活性。AC 水凝胶表现出类骨的粘弹性，这使得 AC 水凝胶具有成骨诱导性。在修复过程中，生物活性双膦酸盐基团加速钙固定，加速新形成骨的矿化。同时，AC 水凝胶的表面电荷特性也防止纤维囊形成，从而保证了骨整合。我们的体外数据强烈表明，AC 水凝胶是一种优异的基质，可诱导大鼠骨髓间充质干细胞的成骨作用。更重要的是，以下体内实验进一步证明，AC 水凝胶无需封装种子细胞或应用外部模拟信号，即可达到令人满意的骨再生效果。这些令人兴奋的结果表明，我们的 AC 水凝胶是一种很有前途的骨再生支架。我们的工作还可以启发组织再生用生物材料支架的组成和结构设计。
