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Sequentially Moldable and Bondable Four-Dimensional Hydrogels Compatible with Cell Encapsulation.

ABSTRACT: Hydrogels have captivated the attention of several research and industry segments, including bioengineering, tissue engineering, implantable/wearable sensors and actuators, bioactive agent delivery, food processing, and industrial processes optimization. A common limitation of these systems is their fixed shape. The concept of hydrogel moldability is often assigned to the injectability potential of liquid precursors, and this feature is often lost right after hydrogel formation. Hydrogel modulation is a recent trend that advocates the importance of designing materials with shape fitting ability targeting on-demand responses or defect filling purposes. Here, we present a compliant and cell encapsulation-compatible hydrogel prepared from unmodified natural origin polymers with the ability to undergo extreme sequential shape alterations with high recovery of its mechanical properties. Different fragments of these hydrogels could be bonded together in spatiotemporally controlled shape- and formulation-morphing structures. This material is prepared with affordable off-the-shelf polysaccharides of natural origin using a mild and safe processing strategy based solely on polyelectrolyte complexation followed by an innovative partial coacervate compaction and dehydration step. These unique hydrogels hold potential for multifield industrial and healthcare applications. In particular, they may find application as defect filling agents or highly compliant wound healing patches for cargo release and/or cell delivery for tissue regeneration and cell-based therapies.

SUBMITTER: Oliveira MB

PROVIDER: S-EPMC6450509 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Sequentially Moldable and Bondable Four-Dimensional Hydrogels Compatible with Cell Encapsulation.

Oliveira Mariana B MB Bastos Henrique X S HXS Mano João F JF Mano João F JF

Biomacromolecules 20180504 7

Hydrogels have captivated the attention of several research and industry segments, including bioengineering, tissue engineering, implantable/wearable sensors and actuators, bioactive agent delivery, food processing, and industrial processes optimization. A common limitation of these systems is their fixed shape. The concept of hydrogel moldability is often assigned to the injectability potential of liquid precursors, and this feature is often lost right after hydrogel formation. Hydrogel modulat ...[more]

PMID: 29698598

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Project description:While the gold standard for inducing mesenchymal stem cell (MSC) chondrogenesis utilizes pellet culture, most tissue engineering strategies for cartilage regeneration encapsulate MSCs as single cells, partially due to the technical challenge to homogeneously encapsulate cell pellets in three-dimensional (3D) hydrogels. It remains unclear whether encapsulating MSCs as single cell suspension or cell aggregates in 3D hydrogels would enhance MSC-based cartilage formation. In this study, we determined that the optimal size of MSC micropellets (?Pellets) that can be homogeneously encapsulated in hydrogels with high cell viability is 100 cells/pellet. Using optimized ?Pellet size, MSCs were encapsulated either as single cell suspension or ?Pellets in four soft hydrogel formulations with stiffness ranging 3-6?kPa. Regardless of hydrogel formulations, single cell encapsulation resulted in more neocartilage deposition with improved mechanical functions over ?Pellet encapsulation. For single cell encapsulation, polyethylene glycol (PEG) hydrogels containing chondroitin sulfate led to the most cartilage matrix deposition, with compressive modulus reaching 211?kPa after only 21 days, a range approaching the stiffness of native cartilage. The findings from this study offer valuable insights on guiding optimal method design for MSCs and hydrogel-based cartilage regeneration. The optimized ?Pellet encapsulation method may be broadly applicable to encapsulate other stem cell types or cancer cells as aggregates in hydrogels. Impact Statement While the gold standard for inducing mesenchymal stem cell (MSC) chondrogenesis utilizes pellet culture, it remains unclear whether encapsulating MSCs as cell pellets in three-dimensional hydrogels would enhance MSC-based cartilage formation. In this study, we determined the optimal size of MSC micropellet (?Pellet) that can be homogeneously encapsulated in hydrogels with high cell viability. Unexpectedly, single cell encapsulation resulted in more robust new cartilage formation than ?Pellet encapsulation. Furthermore, tuning hydrogel formulation led to rapid cartilage regeneration with stiffness approaching that of native cartilage. The findings from this study would facilitate clinical translation of MSCs and hydrogel-based therapies for cartilage regeneration with optimized parameters.

Dataset Information

Sequentially Moldable and Bondable Four-Dimensional Hydrogels Compatible with Cell Encapsulation.

Publications

Sequentially Moldable and Bondable Four-Dimensional Hydrogels Compatible with Cell Encapsulation.

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