Covalently cross linked hydrogels and methods of making and using same

Abstract

A thiol-yne polymeric material and methods for producing said polymers are disclosed. The material is produced by the radically mediated polymerization of monomers having alkyne and thiol functional groups. The alkyne moiety, internal or terminal, may react with one or two thiols. Degradable monomers may be used to form degradable polymers.

1 . A composition comprising a polymer comprising two or more types of monomers wherein at least a first monomer comprises at least two thiol moieties and at least a second monomer comprises at least one alkyne moiety and wherein the first and second monomers are crosslinked at bonds between the thiol and alkyne moieties. 
     
     
         2 . The composition of  claim 1 , wherein the first monomer comprises at least 3, 4, 5, 6, 7, 8, 9 or 10 thiol moieties. 
     
     
         3 . The composition of  claim 1 , wherein the second monomer comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 alkyne moieties. 
     
     
         4 . The composition of  claim 1 , wherein the first and/or second monomer are derivatized to include a thiol or alkyne moiety. 
     
     
         5 . The composition of  claim 1 , wherein the first and/or second monomer is selected from the group consisting of poly(lactic acid) (PLA), polyglycolide (PGA), copolymers of PLA and PGA (PLGA), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(ethylene oxide), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers, meroxapols), poloxamines, polyanhydrides, polyorthoesters, poly(hydroxy acids), polydioxanones, polycarbonates, polyaminocarbonates, poly(vinyl pyrrolidone), poly(ethyl oxazoline), carboxymethyl cellulose, hydroxyalkylated celluloses such as hydroxyethyl cellulose and methylhydroxypropyl cellulose, and natural polymers such as nucleic acids, polypeptides, polysaccharides or carbohydrates such as polysucrose, hyaluranic acid, dextran and similar derivatives thereof, heparan sulfate, chondroitin sulfate, heparin, or alginate, and proteins including without limitation gelatin, collagen, albumin, or ovalbumin, or copolymers, or blends thereof. In particularly preferred embodiments, the monomers can be selected from poly(lactic acid) (PLA), poly(vinyl alcohol) (PVA), and poly(ethylene glycol) (PEG). 
     
     
         6 . The composition of  claim 1 , wherein the composition comprises a hydrogel. 
     
     
         7 . The composition of  claim 5 , wherein the hydrogel comprises more than 50% solvent by weight. 
     
     
         8 . The composition of  claim 8 , wherein the hydrogel comprises between 50 and 95% water by weight. 
     
     
         9 . The composition of  claim 1 , wherein the first or second monomers are degradable. 
     
     
         10 . The composition of  claim 9 , wherein the degradable monomer is hydrolytically, chemically or enzymatically degradable. 
     
     
         11 . The composition of  claim 1 , wherein the first monomer comprises a peptide. 
     
     
         12 . The composition of  claim 11 , wherein the peptide is enzymatically degradable. 
     
     
         13 . The composition of  claim 12 , wherein the enzyme is a protease. 
     
     
         14 . The composition of  claim 11 , wherein the peptide is selected from the group consisting of adhesion peptides (such as RGD adhesion sequence), growth factors, hormones, antihormones, signaling compounds, enzymes, serum proteins, albumins, macroglobulins, globulins, agglutinins, lectins, extracellular matrix proteins, antibodies, and antigens. 
     
     
         15 . The composition of  claim 1 , further comprising an agent that has a biological function or activity. 
     
     
         16 . The composition of  claim 15 , wherein the agent is a peptide selected from the group consisting of adhesion peptides (such as RGD adhesion sequence), growth factors, hormones, antihormones, signaling compounds, enzymes, serum proteins, albumins, macroglobulins, globulins, agglutinins, lectins, extracellular matrix proteins, antibodies, and antigens. Types of non-peptide agents that can be incorporated into the polymeric material include analgesics, antipyretics, nonsteriodal antiinflammatory drugs, antiallergics, antibacterial drugs, antianemia drugs, cytotoxic drugs, antihypertensive drugs, dermatological drugs, psychotherapeutic drugs, vitamins, minerals, anorexiants, dietetics, antiadiposity drugs, carbohydrate metabolism drugs, protein metabolism drugs, thyroid drugs, antithyroid drugs, and coenzymes. 
     
     
         17 . The composition of  claim 1 , further comprising an agricultural chemical. 
     
     
         18 . The composition of  claim 17 , wherein the agricultural chemical is selected from the group consisting of fungicides, herbicides, fertilizers, pesticides, carbohydrates, nucleic acids, organic molecules, and inorganic biologically active molecules. 
     
     
         19 . A method for producing the composition of  claim 1  comprising
 (a) providing the first and second monomers; 
 (b) mixing the first and second monomers with a photoinitiator in solvent; and 
 (c) exposing the first and second monomers and photoinitiator to light, thereby producing the composition of  claim 1 . 
 
     
     
         20 . The method of  claim 19 , wherein the photoinitiator is selected from the group consisting of Irgacure 2959, 184 and 651. 
     
     
         21 . The method of  claim 19 , wherein the light is ultraviolet light. 
     
     
         22 . The method of  claim 21 , wherein the ultraviolet light has a wavelength between 300 and 400 nm. 
     
     
         23 . The method of  claim 19 , wherein the exposure to light lasts for less than two, five or 20 minutes. 
     
     
         24 . The method of  claim 19 , wherein the solvent is present at greater than 50% of the mixture of the first and second monomer, photoinitiator and solvent. 
     
     
         25 . A method of culturing cells comprising growing the cells on the composition of  claim 1 . 
     
     
         26 . The method of  claim 25 , wherein the cells are mammalian cells. 
     
     
         27 . The method of  claim 26 , wherein the cells are human cells. 
     
     
         28 . The method of  claim 25 , wherein the cells are primary cells. 
     
     
         29 . The method of  claim 25 , wherein the cells are stem cells. 
     
     
         30 . A kit comprising the composition of  claim 1 . 
     
     
         31 . The kit of  claim 30 , further comprising photoinitiator.