Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter‐particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter‐particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene‐modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide‐containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter‐particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post‐processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter‐particle crosslinking to enhance injectable granular hydrogels.
This content will become publicly available on August 31, 2024
Injectable hydrogels are increasingly explored for the delivery of cells to tissue. These materials exhibit both liquid‐like properties, protecting cells from mechanical stress during injection, and solid‐like properties, providing a stable 3D engraftment niche. Many strategies for modulating injectable hydrogels tune liquid‐ and solid‐like material properties simultaneously, such that formulation changes designed to improve injectability can reduce stability at the delivery site. The ability to independently tune liquid‐ and solid‐like properties would greatly facilitate formulation development. Here, such a strategy is presented in which cells are ensconced in the pores between microscopic granular hyaluronic acid (HA) hydrogels (microgels), where elasticity is tuned with static covalent intra‐microgel crosslinks and flowability with mechanosensitive adamantane‐cyclodextrin (AC) inter‐microgel crosslinks. Using the same AC‐free microgels as a 3D printing support bath, the location of each cell is preserved as it exits the needle, allowing identification of the mechanism driving mechanical trauma‐induced cell death. The microgel AC concentration is varied to find the threshold from microgel yielding‐ to AC interaction‐dominated injectability, and this threshold is exploited to fabricate a microgel with better injection‐protecting performance. This delivery strategy, and the balance between intra‐ and inter‐microgel properties it reveals, may facilitate the development of new cell injection formulations.
more » « less- NSF-PAR ID:
- 10466053
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 35
- Issue:
- 44
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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