Hydrogels in the clinic

Abstract

Injectable hydrogels are one of the most widely investigated and versatile technologies for drug delivery and tissue engineering applications. Hydrogels' versatility arises from their tunable structure, which has been enabled by considerable advances in fields such as materials engineering, polymer science, and chemistry. Advances in these fields continue to lead to invention of new polymers, new approaches to crosslink polymers, new strategies to fabricate hydrogels, and new applications arising from hydrogels for improving healthcare. Various hydrogel technologies have received regulatory approval for healthcare applications ranging from cancer treatment to aesthetic corrections to spinal fusion. Beyond these applications, hydrogels are being studied in clinical settings for tissue regeneration, incontinence, and other applications. Here, we analyze the current clinical landscape of injectable hydrogel technologies, including hydrogels that have been clinically approved or are currently being investigated in clinical settings. We summarize our analysis to highlight key clinical areas that hydrogels have found sustained success in and further discuss challenges that may limit their future clinical translation. K E Y W O R D S clinics, drug delivery, FDA, injectable materials, marketed products, regenerative, translational medicine

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships

“…Hydrogels are polymer networks swollen in water or biological fluids that can be used in a range of biomedical applications such as drug delivery carriers ( 1 ), biosensors ( 2 ), and soft tissue scaffolds ( 3 ). The functional properties of a hydrogel originate from its structure at multiple length scales ( 4 ), with mounting evidence for the importance of physical properties in controlling biological behavior ( 5 – 7 ).…”

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

“…This is particularly important for the clinical translation of hydrogel‐based carriers, implants, and devices, where the selection of the hydrogel base material, hydrogelation mechanism, and trigger are all highly dependent on the envisaged application and route of administration. Many hydrogel products have reached the market, [ 279 ] as part of surgical sealants (e.g., COSEAL, EVICEL fibrin sealant, or ReSURE ocular sealant), [ 280 ] wound dressings (e.g., Granugel), [ 281 ] antibacterial coatings (e.g., DAC), [ 282 ] dermal fillers (e.g., Restylane), [ 283 ] and cartilage repair matrices (e.g., CaReS). [ 284 ] Meanwhile, ongoing and future clinical trials are testing injectable hydrogel formulations for the treatment of knee osteoarthritis [ 285,286 ] and cartilage defects, [ 287 ] antibiotic‐loaded hydrogel coatings for hip implants, [ 288 ] and tissue‐marking hydrogels for radiotherapy.…”

“…[ 289 ] However, many clinical challenges remain, particularly surrounding scale‐up costs, conformity to good manufacturing processes, and complex regulatory and approval procedures. [ 279 ] In light of these considerations, hydrogel products with a simple design and based on materials already in use in the clinic may benefit from a more straightforward bench‐to‐bedside translation and the delivery of real patient benefit. [ 290 ]…”

Engineering Smart Targeting Nanovesicles and Their Combination with Hydrogels for Controlled Drug Delivery

“…There exist many challenges and hurdles that need to be surpassed before clinically approving a hydrogel product. These challenges were recently discussed in detail in a comprehensive review by Mandal et al [ 144 ]. Nevertheless, in recent years, the FDA has approved a number of marketed hydrogel-based products such as Belotero balance ® , Revanesse ® Versa TM , SpaceOAR ® , Teosyal ® RHA, Radiesse ® , and TraceIT ® [ 144 , 145 ].…”

“…These challenges were recently discussed in detail in a comprehensive review by Mandal et al [ 144 ]. Nevertheless, in recent years, the FDA has approved a number of marketed hydrogel-based products such as Belotero balance ® , Revanesse ® Versa TM , SpaceOAR ® , Teosyal ® RHA, Radiesse ® , and TraceIT ® [ 144 , 145 ]. Depending on the added drugs and bioactive compounds, hydrogels can be classified Class I, II, or III medical devices by the FDA [ 146 ].…”