Acrylates are an important class of medical adhesives, with applications as bone and dental cements (methyl acrylate) as well as liquid sutures (cyanoacrylate). Unfortunately, acrylate monomers exhibit significant cytotoxicity, largely due to their high reactivity, causing irritation and morbidity of soft tissues and in some cases, severe allergic reaction.[1][2] To address these concerns, a family of modified acrylate monomers have been developed by conjugating functional therapeutic moieties to the acrylate carbonyl (see Figure 1). By covalently linking therapeutics to acrylate monomers, patient discomfort can be decreased, monomer toxicity is reduced, and release of therapeutics over time is predictable and tunable. Using a variety of chemical bonds, different controlled release profiles and permanent covalent attachment have been accessed. The release profile can further be tuned by creating composite adhesives with a mixture of therapeutics and/or types of covalent linkages. These modified acrylates are inspired by current commercial adhesives, butyl and octyl acrylate esters that are better tolerated than methyl acrylate in vivo,[3] but further streamline the healing process by incorporating local and injury-specific therapeutic delivery.
These adhesives can easily be tailored to a broad range of applications without sacrificing core functionality. Several non-steroidal anti-inflammatory drug derivatives, including ibuprofen‑methacrylate and acetaminophen‑methacrylate, have been synthesized that demonstrate chemistry-dependent controlled release. Addition of the drug moiety to the methacrylate backbone does not compromise adhesive strength and has been shown to actually improve gel times for composite materials with ethyl cyanoacrylate. Adhesives with analgesic and anti-inflammatory properties are useful for providing immediate and/or extended pain relief for patients requiring wound closure, such as after surgery. Further, therapeutic adhesives can be used to enhance the interface between implanted biomedical devices and the body, and in regenerative medicine, can work in tandem with resorbable biomaterials to direct the healing process. Modified acrylates carrying SVAK-12, a small synthetic molecule known to enhance the potency of BMP-2 which in turn promotes osteogenesis,[4] or N-acetyl cysteine, which has been shown to induce osteoblastic differentiation and protect cells from oxidative stress,[5][6] would complement bone graft and bone graft-substitute therapies for critical orthopedic injuries. Such materials bring sophisticated controlled release technology to the field of medical adhesives, providing both convenient closure or fixation and improved healing.
References:
[1] Santerre, J. P.; Shajii, L.; Leung, B. W. Crit. Rev. Oral Biol. Med. 2001, 12 (2), 136.
[2] Drucker, A. M.; Pratt, M. D. Dermat. Contact Atopic Occup. Drug 2011, 22 (2), 98.
[3] Gosavi, S. S.; Gosavi, S. Y.; Alla, R. K. Dent. Res. J. 2010, 7 (2), 82.
[4] Wong, E.; Sangadala, S.; Boden, S. D.; Yoshioka, K.; Hutton, W. C.; Oliver, C.; Titus, L. J. Bone Joint Surg. Am. 2013, 95 (5), 454.
[5] Kato, S.; Sangadala, S.; Tomita, K.; Titus, L.; Boden, S. D. Mol. Cell. Biochem. 2011, 349 (1-2), 97.
[6] Ueno, T.; Yamada, M.; Igarashi, Y.; Ogawa, T. J. Biomed. Mater. Res. A 2011, 99A (4), 523.