Evaluation of Therapeutic Collagen-Based Biomaterials in the Infarcted Mouse Heart by Extracellular Matrix Targeted MALDI Imaging Mass Spectrometry.
Evaluation of Therapeutic Collagen-Based Biomaterials in the Infarcted Mouse Heart by Extracellular Matrix Targeted MALDI Imaging Mass Spectrometry.
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DOI：
10.1021/jasms.1c00189
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发表时间：
2021-12-01
影响因子：
3.2
通讯作者：
Angel PM
中科院分区：
文献类型：
--
作者：
Clift CL;McLaughlin S;Muñoz M;Suuronen EJ;Rotstein BH;Mehta AS;Drake RR;Alarcon EI;Angel PM
本研究的目的是制定在梗死小鼠心脏内定位人类胶原基水凝胶的策略，并分析其对内源性细胞外基质（ECM）重塑的影响。胶原蛋白是一种天然聚合物，由于其生物相容性、细胞渗透性和生物降解性，被广泛用于生物工程水凝胶中。然而，如果不使用标记技术，来源于水凝胶的胶原肽很难与组织内的内源性ECM区分开来。成像质谱是一种强大的工具，能够可视化合成和天然聚合物分子结构，但在表面表征之外的生物材料领域尚未得到充分利用。在这项研究中，我们的团队利用最近开发的基质辅助激光解吸/电离成像质谱（MALDI IMS）技术，酶促靶向内源性和水凝胶来源的组织微环境中的胶原和其他ECM肽。利用荧光显微镜和ECM-IMS技术的多模态方法，我们能够可视化和相对量化梗死小鼠心脏中定位于治疗性水凝胶注射部位的大量胶原肽。组织上MALDI MS/MS用于推定鉴定胶原肽羟基脯氨酸位点占用位点，这是一种翻译后修饰，对胶原三螺旋稳定性至关重要。此外，该技术可以推测鉴定超过35种内源性表达的ECM肽，这些肽在水凝胶注射的小鼠心脏中表达。我们的研究结果为使用MALDI-IMS评估胶原基生物材料的治疗应用提供了证据。
The goal of this study was to develop strategies to localize human collagen-based hydrogels within an infarcted mouse heart, as well as analyze its impact on endogenous extracellular matrix (ECM) remodeling. Collagen is a natural polymer that is abundantly used in bioengineered hydrogels because of its biocompatibility, cell permeability, and biodegradability. However, without the use of tagging techniques, collagen peptides derived from hydrogels can be difficult to differentiate from the endogenous ECM within tissues. Imaging mass spectrometry is a robust tool capable of visualizing synthetic and natural polymeric molecular structures yet is largely underutilized in the field of biomaterials outside of surface characterization. In this study, our group leveraged a recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technique to enzymatically target collagen and other ECM peptides within the tissue microenvironment that are both endogenous and hydrogel-derived. Using a multimodal approach of fluorescence microscopy and ECM-IMS techniques, we were able to visualize and relatively quantify significantly abundant collagen peptides in an infarcted mouse heart that were localized to regions of therapeutic hydrogel injection sites. On-tissue MALDI MS/MS was used to putatively identify sites of collagen peptide hydroxyproline site occupancy, a post-translational modification that is critical in collagen triple helical stability. Additionally, the technique could putatively identify over 35 endogenously expressed ECM peptides that were expressed in hydrogel-injected mouse hearts. Our findings show evidence for the use of MALDI-IMS in assessing the therapeutic application of collagen-based biomaterials.
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影响因子：
3.4
作者：
Parenteau-Bareil R;Gauvin R;Berthod F
通讯作者：
Berthod F
影响因子：
14
作者：
Blackburn, Nick J. R.;Sofrenovic, Tanja;Suuronen, Erik J.
通讯作者：
Suuronen, Erik J.
影响因子：
21.8
作者：
通讯作者：
--
影响因子：
41.2
作者：
通讯作者：
--
影响因子：
4.6
作者：
Clift CL;Su YR;Bichell D;Jensen Smith HC;Bethard JR;Norris-Caneda K;Comte-Walters S;Ball LE;Hollingsworth MA;Mehta AS;Drake RR;Angel PM
通讯作者：
Angel PM