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先进的甲基丙烯酰基和乙酰基修饰生物分子配方,以实现可打印水凝胶溶胀和硬度的独立控制。

Advanced formulation of methacryl- and acetyl-modified biomolecules to achieve independent control of swelling and stiffness in printable hydrogels.

机构信息

Fraunhofer-Institute for Interfacial Engineering and Biotechnology IGB, Nobelstraße 12, 70569, Stuttgart, Germany.

Institute of Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Nobelstraße 12, 70569, Stuttgart, Germany.

出版信息

J Mater Sci Mater Med. 2019 Mar 6;30(3):35. doi: 10.1007/s10856-019-6231-0.

DOI:10.1007/s10856-019-6231-0
PMID:30840139
Abstract

Biobased hydrogels are considered to mimic native extracellular matrix due to their high water content and are considered as adequate matrices for cell encapsulation. However, the equilibrium degree of swelling (EDS) and stiffness of simple hydrogel formulations are typically confined: Increasing polymer concentration results in increasing stiffness and simultaneously decreasing EDS. The aim of this contribution was to decouple this standard correlation between polymer content, stiffness and EDS as well as the assembly of hydrogels with graded composition of hydrogels by layer-wise printing. We investigated two sets of formulations, which consisted of three different compositions with increasing total biopolymer concentration (10.6%, 11.5%, 13.0%). Within these compositions the amount of gelatin methacryloyl acetyl (GMA) was constant (10%), whereas the proportion of methacrylated hyaluronic acid and chondroitin sulfate increased. In the first set of formulations GMA with one fixed degree of methacryloylation (DM) was used, whereby the storage modulus (G') increased from ~10 to ~25 kPa and the EDS decreased from ~700 to ~600%. In the second set of formulations we gradually lowered the DM of the GMA in parallel to increase of polymer concentration and achieved an increase of both, G' from ~11 to ~18 kPa and EDS from ~690 to ~790%. By dispensing these compositions, we created a glycosaminoglycan-graded hydrogel. We proved the cytocompatibility of the dispensing process, the used photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate, and layer-wise UVA irradiation. Glycosaminoglycan gradient was proved stable for 28 d,encapsulated chondrocytes were viable and produced new matrix.

摘要

生物基水凝胶由于其高含水量而被认为模拟天然细胞外基质,并被认为是细胞包封的合适基质。然而,简单水凝胶配方的平衡溶胀度 (EDS) 和刚性通常受到限制:增加聚合物浓度会导致刚性增加,同时 EDS 降低。本研究的目的是分离聚合物含量、刚度和 EDS 之间的这种标准相关性,以及通过分层打印组装具有梯度组成的水凝胶。我们研究了两组配方,它们由三种不同组成组成,总生物聚合物浓度逐渐增加(10.6%、11.5%、13.0%)。在这些组成中,明胶甲基丙烯酰基乙酰基(GMA)的含量保持不变(10%),而甲基丙烯酰化透明质酸和硫酸软骨素的比例增加。在第一组配方中,使用了一种固定甲基丙烯酰化度(DM)的 GMA,其中储能模量(G')从10kPa 增加到25kPa,EDS 从700 降低到600%。在第二组配方中,我们逐渐降低 GMA 的 DM 以增加聚合物浓度,并实现了 G'从11kPa 增加到18kPa 和 EDS 从690 增加到790%。通过分配这些成分,我们创建了一种糖胺聚糖梯度水凝胶。我们证明了分配过程、所用光引发剂二苯甲酮-2,4,6-三甲基苯膦酸锂和逐层 UVA 照射的细胞相容性。糖胺聚糖梯度在 28 天内保持稳定,包封的软骨细胞存活并产生新基质。

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本文引用的文献

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Physical Interactions Strengthen Chemical Gelatin Methacryloyl Gels.物理相互作用增强化学甲基丙烯酰化明胶凝胶。
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Stretchable collagen-coated polyurethane-urea hydrogel seeded with bladder smooth muscle cells for urethral defect repair in a rabbit model.可拉伸的胶原蛋白涂覆的聚氨酯脲水凝胶,种植有膀胱平滑肌细胞,用于兔模型的尿道缺损修复。
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Biofabrication. 2017 Nov 14;9(4):044103. doi: 10.1088/1758-5090/aa91ec.
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Methacrylated gelatin and mature adipocytes are promising components for adipose tissue engineering.甲基丙烯酸化明胶和成熟脂肪细胞是脂肪组织工程中有前景的组成部分。
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