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含骨基质颗粒的光交联水凝胶在牙本质组织工程中的应用进展。

Photo-crosslinkable hydrogel incorporated with bone matrix particles for advancements in dentin tissue engineering.

机构信息

Department of Operative Dentistry, Endodontics, and Dental Materials, School of Dentistry, University of São Paulo-USP, Bauru, Brazil.

Department of Anatomy, Biology Institute, University of Campinas-IB/Unicamp, São Paulo, Brazil.

出版信息

J Biomed Mater Res A. 2024 Dec;112(12):2273-2288. doi: 10.1002/jbm.a.37777. Epub 2024 Jul 17.


DOI:10.1002/jbm.a.37777
PMID:39015005
Abstract

The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration.

摘要

本研究的目的是制备可注射的光交联生物材料,使用明胶甲基丙烯酰(GelMA)水凝胶,结合脱细胞骨基质(BMdc)和脱蛋白(BMdp)牛骨基质。这些基质旨在作为牙本质再生的生物活性支架。首先选择 GelMA 水凝胶制备的参数,然后以 1%(w/v)的比例加入 BMdc 和 BMdp。还包括纳米羟基磷灰石(nHA)作为对照。进行了理化特性表征,傅里叶变换红外(FTIR)分析表明,矿物相与 GelMA 复合,BMdc 通过化学键与明胶的酰胺基团结合。多孔结构在加入 BMdc 后得以保留,骨颗粒与孔一起嵌入。相反,矿物相位于孔口内部,影响了孔隙率的程度。即使在 I 型胶原酶介导的酶促挑战条件下,矿物相也没有改变 GelMA 的降解性,允许水凝胶注射和增加机械强度。随后,将人牙髓细胞(HDPCs)接种到水凝胶上。细胞保持存活和增殖,无论 GelMA 组成如何。所有矿物相均显著增加碱性磷酸酶活性和矿化基质沉积。然而,GelMA-BMdc 表现出更高的细胞表达值,显著超过所有其他配方。总之,我们的结果表明,GelMA-BMdc 产生了多孔且稳定的水凝胶,与 HDPCs 接触时能够增强成牙本质细胞的分化和矿化沉积,因此具有牙本质再生的潜力。

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