Preparation of composite gels, polymer scaffolds, aggregates and films comprising soluble cross-linked chitosan and uses thereof

An aqueous gelling solution comprising a gel-forming polymer from about 0.3% to about 25% (w/w), a biocompatible acid and a soluble cross-linked chitosan at 0.001% and 20% (w/w),

• wherein said soluble cross-linked chitosan is fully soluble at pH <5.5 in aqueous solution at room temperature and said cross-linked chitosan having been formed by reacting chitosan with an acrylic compound of Formula (I) to form an acylation product and reacting the acylation product in the presence of a base:
• wherein R1 is a halogen or any other leaving group that upon removal, ensures acylation of an amino group, anhydride, mixed anhydrides, N-hydroxysuccinimide, pentachlorophenol, 2-nitro-4-sulfophenol esters and other similar leaving groups;
• R2, R3 and R4 are independently selected from H;
• optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkynyl, optionally substituted heterocycloalkyl;
• optionally substituted aryl, optionally substituted heteroaryl and optionally substituted aryl C1-C6 alkyl;
• wherein the term “substituted” refers to groups substituted with from 1 to 5 substituents selected from the group consisting of halogen, —COOR′, —NR′R″, —O, —OR′, —COR′, —CONR′R″, —SR′, —SO3R′, —SO2NR′R″, —SOR′, —SO2R′, —NO2, or —CN;
• or R1 and R2 or R1 and R3, or R1 and R4 together form an optionally substituted 4-24 membered aryl, heteroaryl, cycloalkyl or heterocycloalkyl,
• wherein said biocompatible acid is selected from acetic acid, citric acid, propionic acid, caproic acid, aminocaproic acid, succinic acid, glutaric acid, lactic acid, malic acid, tartaric acids, cinnamon acid and benzoic acid, sorbic acid, oxalic acid, salicylic acid, acetylsalicylic and cinnamon acid and
• wherein said soluble cross-linked chitosan is characterized by the presence of a hydrolysis product of Formulae IIIa or IIIb
• when said cross-linked chitosan is subjected to an acidic hydrolysis and R2, R2′, R3, R3′, R4 and R4′ are independently selected from H;
• optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkynyl, optionally substituted heterocycloalkyl;
• optionally substituted aryl, optionally substituted heteroaryl and optionally substituted aryl C1-C6 alkyl;
• wherein the term “substituted” refers to groups substituted with from 1 to 5 substituents selected from the group consisting of halogen, —COOR′, —NR′R″, ═O, —OR′, —COR′, —CONR′R″, —SR′, —SO3R′, —SO2NR′R″, —SOR′, —SO2R′, —NO2, or —CN;
• or R1 and R2 or R1 and R3, or R1 and R4 together form an optionally substituted 4-24 membered aryl, heteroaryl, cycloalkyl or heterocycloalkyl.