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.

Keywords: FDA; clinics; drug delivery; injectable materials; marketed products; regenerative; translational medicine.

FIGURE 1

Comprehensive analysis of hydrogels in clinical trials. Clinical trials which mentioned a hydrogel were identified using http://clinicaltrials.gov. Trials where the hydrogel was not used for a diagnostic or therapeutic purpose were removed. Trials which investigated the hydrogel cleaning solution, or another aspect of the hydrogel packaging, were also removed. In total, there were 425 clinical trials involving hydrogel materials. The primary clinical application of hydrogel materials was for soft contact lenses (202 unique clinical trials). With contact lenses excluded from further analysis, there were 223 clinical trials, spanning diverse medical applications. Trials which used the hydrogel as a tissue substitute, or a mechanical support to augment existing tissues (Regen Tissue) were analyzed separately from those which used hydrogels as a dressing or barrier to facilitate healing of an abrasion, burn, or ulcer (Regen wound). Of the 223 non‐lens hydrogel clinical trials, 8 used a hydrogel coil (cardiovascular application), 99 used a hydrogel patch, and 116 used a bulk hydrogel. Of the 116 bulk hydrogels, 31 were delivered via injection. Within the domain of injectable hydrogels, there are 28 approved clinical products and 31 devices in clinical trial (for full detail, see Tables 1 and 2). Within each hydrogel grouping (i.e., patch, bulk, injectable), we also stratified clinical trials by material origin (i.e., natural, synthetic, or unknown). Material origin was determined from either the clinical trial description or the device's U.S. patent. Solid lines denote categorization or clarification of a group, while dotted lines represent extraction of a particular subset

FIGURE 2

Design of hydrogels to overcome biophysical and biochemical challenges. When designing a new hydrogel, one determines the chemical functionality and chain rigidity by either selecting or synthesizing a proper backbone material (e.g., hyaluronic acid, polyethylene glycol, polyacrylate). The molecular weight of that linear backbone, the mechanism of crosslinking/gelation, as well as the molecular weight between crosslinks (i.e., extent of crosslinking) will determine the physical properties of the system. The combination of these chemical and physical identities will determine the gels’ mechanical integrity, solute transport properties, and interactions with host cells. Shown above are the clinical applications of (top) intra‐articular or subcutaneous injection, (middle) drug elution from an injected hydrogel depot, and (bottom) cell infiltration of an injected hydrogel scaffold