Hydrogel compositions and uses thereof

A method of making a cross-linked polymer, said method comprising:

• (i) providing a first composition comprising a compound of formula (I):
• (ii) providing a second composition comprising a multimeric polymeric cross-linker bearing one or more terminal oxyamine groups;
• and
• (iii) combining the first composition and the second composition to form a mixture,
• wherein
• HAP is a hyaluronan polymer;
• and
• K is a moiety covalently linked to the hyaluronan polymer having the structure of formula (Ia) or formula (Ib):
• wherein
• RX is C1-20 alkylene, C2-20 alkenylene, C2-20 alkynylene, C1-20 heteroalkylene, C2-20 heteroalkenylene, or C2-20 heteroalkynylene, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol;
• and
• R1 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 heteroalkyl, C2-6 heteroalkenyl, C2-6 heteroalkynyl, C3-10 carbocyclyl, C6-10 aryl, C2-9 heterocyclyl, or C2-9 heteroaryl, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol,
• or a salt thereof.

A compound of formula (V):

• wherein
• HAP is a hyaluronan polymer;
• and
• OA is a moiety covalently linked to the hyaluronan polymer having the structure of formula (Va):
• wherein
• RW is polypeptide, C1-20 alkylene, C2-20 alkenylene, C2-20 alkynylene, C1-20 heteroalkylene, C2-20 heteroalkenylene, or C2-20 heteroalkynylene, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol;
• and
• R3 is H, C1-6 alkyl, or C1-6 heteroalkyl, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol,
• or a salt thereof.

A cross-linked polymer of (i) a hyaluronan polymer and (ii) a multimeric polymeric cross-linker conjugated through at least one linkage group of formula (VIII-i) or formula (VIII-ii):

• wherein
• R4 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 heteroalkyl, C2-6 heteroalkenyl, C2-6 heteroalkynyl, C3-10 carbocyclyl, C6-10 aryl, C2-9 heterocyclyl, or C2-9 heteroaryl, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol;
• RW is a moiety covalently linked to the hyaluronan polymer;
• RW is polypeptide, C1-20 alkylene, C2-20 alkenylene, C2-20 alkynylene, C1-20 heteroalkylene, C2-20 heteroalkenylene, or C2-20 heteroalkynylene, any of which is optionally substituted with one or more of oxo, halogen, hydroxyl, alkoxy, azido, cyano, nitro, amino, and thiol;
• and
• RZ is a fragment formed from the multimeric polymeric cross-linker,
• or salt thereof.