Clinical Use of the Self-Assembling Peptide RADA16: A Review of Current and Future Trends in Biomedicine

Abstract

RADA16 is a synthetic peptide that exists as a viscous solution in an acidic formulation. In an acidic aqueous environment, the peptides spontaneously self-assemble into β-sheet nanofibers. Upon exposure and buffering of RADA16 solution to the physiological pH of biological fluids such as blood, interstitial fluid and lymph, the nanofibers begin physically crosslinking within seconds into a stable interwoven transparent hydrogel 3-D matrix. The RADA16 nanofiber hydrogel structure closely resembles the 3-dimensional architecture of native extracellular matrices. These properties make RADA16 formulations ideal topical hemostatic agents for controlling bleeding during surgery and to prevent post-operative rebleeding. A commercial RADA16 formulation is currently used for hemostasis in cardiovascular, gastrointestinal, and otorhinolaryngological surgical procedures, and studies are underway to investigate its use in wound healing and adhesion reduction. Straightforward application of viscous RADA16 into areas that are not easily accessible circumvents technical challenges in difficult-to-reach bleeding sites. The transparent hydrogel allows clear visualization of the surgical field and facilitates suture line assessment and revision. The shear-thinning and thixotropic properties of RADA16 allow its easy application through a narrow nozzle such as an endoscopic catheter. RADA16 hydrogels can fill tissue voids and do not swell so can be safely used in close proximity to pressure-sensitive tissues and in enclosed non-expandable regions. By definition, the synthetic peptide avoids potential microbiological contamination and immune responses that may occur with animal-, plant-, or mineral-derived topical hemostats. In vitro experiments, animal studies, and recent clinical experiences suggest that RADA16 nanofibrous hydrogels can act as surrogate extracellular matrices that support cellular behavior and interactions essential for wound healing and for tissue regenerative applications. In the future, the unique nature of RADA16 may also allow us to use it as a depot for precisely regulated drug and biopharmaceutical delivery.

PuraStat RADA16 Self-Assembling Peptide Reduces Postoperative Abdominal Adhesion Formation in a Rabbit Cecal Sidewall Injury Model

“…RADA16 (acetyl-[arginyl-alanyl-aspartyl-alanyl] 4 -amide tetrahydrochloride) is a unique synthetic peptide that spontaneously self-assembles to form nanofibers in aqueous environments. The RADA16 nanofibers physically cross-link upon contact with blood and tissue fluids to form a biocompatible hydrogel (Edwards Gayle and Hamley, 2017;Zhang, 2017;Lee et al, 2019;Wang et al, 2019;Sankar et al, 2021). Formulations of RADA16 are used globally as a topical hemostat to stop intraoperative bleeding and prevent postoperative bleeding (United States Food and Drug Administration, 2021;3-D Matrix Inc. and Needham, 2014).…”

“…RADA16 is a synthetic 16-amino acid peptide that remains solubilized as discrete β-sheet nanofibers in acidic aqueous solutions, which spontaneously begin cross-linking into complex three-dimensional (3D) hydrogel matrices within seconds after exposure to the physiological pH of blood, interstitial fluid, and lymph (Edwards-Gayle and Hamley, 2017;Zhang, 2017;Lee et al, 2019;Wang et al, 2019;Sankar et al, 2021). RADA16 has been shown to be an effective topical hemostatic agent, and a commercial formulation, PuraStat ® , (Instructions for Use, 2014; 3-D Matrix Europe SAS, Caluireet-Cuire, France) is currently CE marked in Europe, cleared in the US, approved in Japan, and licensed in Australia to control intraoperative bleeding in various surgical procedures including cardiovascular, gastrointestinal (GI), and/or otorhinolaryngological applications (Sankar et al, 2021;3-D Matrix Inc. and Needham, 2014;United States Food and Drug Administration 2021). In some countries, PuraStat is also approved for treating delayed postoperative bleeding.…”

Self-assembling peptide haemostatic gel reduces incidence of pelvic collection after total mesorectal excision: Prospective cohort study

“…A recent review has also mentioned other potential uses of SAP in surgery, namely surgical haemostasis, haemostasis for radiation-induced proctitis, promotion of wound healing and tissue regeneration, and reduction of postoperative adhesions [ 23 ]. Future extended studies should take into consideration some of these new parameters as potential beneficial outcomes for the patients undergoing TME for cancer.…”

Self-Assembling Peptides: From Design to Biomedical Applications

“…Another analogue is PuraDerm ® . This drug is used in the United States as a topical wound dressing for the treatment of superficial or deep wounds like diabetic, decubitus, and leg ulcers or surgical wounds [ 24 ].…”

“…Currently, SAPs are also used as a three-dimensional cell culture [ 21 ]and as biosensors, such as the Fmoc-FF hydrogel-based biosensor [ 22 ]. They are also used in different vaccine formulations, such as Q11 peptide for the intravaginal vaccination [ 23 ], and some of them have already reached the pharmaceutical market [ 24 , 25 , 26 ].…”