Sealants for tissue closure
The invention relates to biodegradable bilayer sealants for tissue closure. The sealants of the invention are composed of two layers with different compliances. The layer in immediate contact with the tissue has high compliance. The second layer located immediately above the first sealant layer has low compliance, i.e. the sealant is much stiffer. The burst pressure of the bilayer sealants is enhanced relative to either a single layer elastic sealant or a single layer stiff sealant. The improved sealant compositions herein provide a water-tight seal, can access hard to reach tears, be applied in a dry or wet environment, are low-swelling, and can repair a range of incision or tear sizes. The bilayer sealants are particularly useful for sutureless dural closure or as adjuncts to sutured dural closure. Also provided herein are methods of preparing and using the biodegradable sealant compositions.
1 . A method for tissue closure comprising:
(a) spraying on a tissue a first layer comprising a biodegradable elastic polymeric composition comprising a multi-arm polyethylene glycol;
(b) allowing the first layer to at least partially cure; and
(c) spraying a second layer on a surface of the biodegradable elastic polymeric composition wherein the second layer comprises a biodegradable stiff polymeric composition comprising a multi-arm polyethylene glycol, and a protein or a peptide,
wherein a ratio of layer thickness of the biodegradable elastic polymeric composition to stiff polymer composition is from about 1:1 to about 3:1; the biodegradable elastic polymeric composition has an elastic modulus of about 19 kPa to about 24 kPa; and the biodegradable stiff polymeric composition has an elastic modulus about less than three-fold the biodegradable elastic polymeric composition;
wherein the first layer and second layer are composed of compatible chemistries, allowing for covalent linkage between the first layer and second layer,
wherein the elastic polymeric composition is characterized by an elongation at failure of at least about 245%, and wherein the stiff polymeric composition is characterized by an elongation at failure of up to about 110%.
2 . The method of claim 1 , wherein the multi-arm polyethylene glycol is selected from the group consisting of 4-arm-PEG-amine, 4-arm-PEG-N-hydroxysuccinimide, 6-arm-PEG-N-hydroxysuccinimide, 4-arm-PEG-succinimidyl glutarate, 4-arm-PEG-succinimidyl carbonate, 4-arm-PEG-acrylate, 4-arm-PEG-succinimidyl valerate, 4-arm-PEG-succinimidyl succinate, 4-arm-PEG-succinimidyl butanoate, 4-arm-PEG-succinimidyl succinamide, 4-arm-PEG-succinimidyl propionate, 4-arm-PEG-sulfosuccinimidylglutarate (SG), 4-arm-PEG-sulfosuccinimidylvalerate, 4-arm-PEG-sulfosuccinimidylcarbonate, 4-arm-PEG-succinimidlyl carboxymethyl ester, 4-arm-PEG-sulfosuccinimidylsuccinate, 4-arm-PEG-sulfosuccinimidylbutanoate, 4-arm-PEG-sulfosuccinimidylsuccinamide, 4-arm-PEG-sulfosuccinimidylpropionate, and 4-arm-PEG-isocyanate, 4-arm-PEG-imidoester, and 4-arm-PEG-maleimide, and combinations of two or more thereof.
3 . The method of claim 1 , wherein the protein is selected from the group consisting of albumin, fibronectin, ovalbumin, lactalbumin, extracellular matrix protein, polylysine, and combinations of two or more thereof.
4 . The method of claim 1 , wherein the biodegradable elastic polymeric composition consists of a 4-arm PEG-Amine, a 4-arm-PEG-succinimidyl glutarate (PEG-SG), water, and a buffer, and wherein the biodegradable stiff polymeric composition consists of albumin, PEG-SG, water, and a buffer.