US 12,246,108 B2
Mussel inspired nanocomposite adhesives for biomedical applications
Yi Hong, Arlington, TX (US); Kytai Nguyen, Arlington, TX (US); Philippe Zimmern, Arlington, TX (US); and Jun Liao, Arlington, TX (US)
Assigned to BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Filed by BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Filed on Oct. 13, 2020, as Appl. No. 17/069,239.
Claims priority of provisional application 62/914,665, filed on Oct. 14, 2019.
Prior Publication US 2021/0106718 A1, Apr. 15, 2021
Int. Cl. A61L 24/04 (2006.01); A61L 24/00 (2006.01); C08G 18/18 (2006.01); C08G 18/22 (2006.01); C08G 18/24 (2006.01); C08G 18/30 (2006.01); C08G 18/32 (2006.01); C08G 18/77 (2006.01)
CPC A61L 24/046 (2013.01) [A61L 24/0015 (2013.01); A61L 24/0042 (2013.01); C08G 18/1808 (2013.01); C08G 18/1833 (2013.01); C08G 18/227 (2013.01); C08G 18/246 (2013.01); C08G 18/307 (2013.01); C08G 18/3206 (2013.01); C08G 18/771 (2013.01)] 17 Claims
 
1. A tissue adhesive composition comprising:
a biodegradable adhesive;
nanoparticles; and
a tissue regenerative agent,
wherein the nanoparticles are loaded with the tissue regenerative agent, and
wherein the composition has a lap shear strength greater than 35 kPa when adhered to a biological tissue to tissue interface for 1 hour,
wherein the biodegradable adhesive comprises a dopamine grafted alginate, polytripeptide (Gly-Tyr-Lys), Mussel Adhesive Protein (MAP), polyethylene glycol (PEG-DOPA), hyaluronic acid (HA) on Pluronic hydrogel, catechol-Ala-Ala-PEG (CAAPEG), poly ((Lys·HBr)x-(DOPA)y), deacetylated chitosan, oxidized and DOPA-functionalized dextran, PEG-dopamine-polycaprolactone (PCL), injectable citrate-based mussel-inspired bioadhesives iCMBAs, anti-bacterial and anti-fungal iCMBAs (AbAf iCs), click iCs, ethylene glycol acrylate methacrylate dopamine (EGAMA-DOPA), poly (dopamine-co-acrylate) (PDA), rfp-1 (MAP), light-activated, mussel protein-based bioadhesive (LAMBA), PEU (poly (CATyr-co-Leu)), PEU (poly (CA-Ser-co-Leu-co-PPG)), POEC-d (octanediol, PEO, citric acid, dopamine), DCTA (gelatin macromer, Fe3+, genipin), a polyester, 4-arm-PEG-DA, 4-arm-PEG-PBA, polypeptide-pluronic-polypeptide, or any combination thereof;
wherein the biodegradable adhesive is present in a concentration of 1 to 40 wt. % and comprises a polymer having a weight average molecular weight of 20,000-200,000;
wherein the nanoparticles comprise poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactide-co-glycolide) (“PLGA”), poly (lactide-co-glycolide) N-hydroxysuccinimide (“PLGA-NHS”), poly (lactide-co-glycolide) polydopamine (“PLGA-Dopa”), polydopamine, hyaluronic acid-dopamine, silica, poly-(ethylene glycol) (PEG), poly (acryl amide) (PAA), poly (vinyl pyrrolidone) (PVP), poly (caprolactone) (PCL), chitosan, poly-alkyl-cyano-acrylates (PAC), gelatin or any combination thereof;
wherein the nanoparticles have an average particle size in any dimension of 50 nm to 500 nm;
wherein the tissue regenerative agent comprises a cell recruitment agent, a tissue growth factor, a protein, a microRNA, an exosome, or any combination thereof;
wherein the tissue regenerative agent comprises a cell recruitment agent; and
wherein the cell recruitment agent is stromal cell derived factor-1 alpha (“SDF-1α”).