Abstract

Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposes—they can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.

Highlights

  • Since their discovery in the 1960s,1 synthetic hydrogels have become increasingly useful for engineering biological systems

  • Studies revealed the usefulness of engineered hydrogels for delivering diverse drugs,[3−5] establishing a field for local controlled release of bioactive compounds.[6−10] In the 1970s, surgeons recognized the utility of hydrogels for reconstructive surgeries,[11,12] and by the 1990s, hydrogels were becoming a foundational technology for tissue regeneration.[13−16] The history of hydrogel materials is well reviewed,[17−19] and the consistent theme has been that hydrogels continue to find new and exciting applications as the underlying technology improves (Figure 2)

  • Alginate hydrogels do not confer any therapeutic benefits in themselves, in contrast to the ROS-reactive platform discussed previously, this study reported that hydrogel delivery improved the efficacy of aPD-1/celecoxib combination therapy compared to injection of the free drugs

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Summary

Paracrine Signaling from Cellularized Hydrogels

Injectable Hydrogels Currently in the Clinic 6.2. Manufacturing and Scale Up Considerations for Translation 7.

INTRODUCTION
MECHANICAL CONSIDERATION FOR DESIGNING INJECTABLE HYDROGELS
Rheological Considerations for Injectable Dynamic Hydrogels
Pre- and Postinjection Constraints of Injectable Hydrogels
Relevant Rheological Properties for Injectability
Rheological Characterization of Injectable Hydrogels
Outlook for Rheological Characterization of Injectable Hydrogels
HYDROGELS FOR DRUG DELIVERY
Considerations for Small Molecule Delivery
Considerations for Nucleic Acid Delivery
Considerations for Protein Delivery
Injectable Hydrogels for Cancer Immunotherapy
Hydrogels for Immunomodulation Beyond Cancer Immunotherapy
HYDROGELS FOR CELLULAR THERAPY
Cell Adhesion to Hydrogels
Hydrogel Degradability to Facilitate Cellular Remodeling and Motility
Tuning Diffusion and Porosity
Cell Delivery Using In Situ Gelation
Cell Delivery Using Dynamic Hydrogels
Applications of Hydrogel Cellular Therapies
OTHER BIOMEDICAL APPLICATIONS OF HYDROGELS
Hydrogels for Surgical Applications
Hydrogel Coatings for Medical Devices
CLINICAL TRANSLATION OF BIOMEDICAL HYDROGELS
Injectable Hydrogels Currently in the Clinic
Manufacturing and Scale Up Considerations for Translation
OPPORTUNITIES FOR HYDROGELS BEYOND BIOMEDICAL APPLICATIONS
Findings
CONCLUSIONS

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