Methods of forming, dissolving, and functionalizing an extracellular matrix gel on demand based on cross-linking, modification, and dissolution of hydrogels using transpeptidase (e.g. sortase) are disclosed. Also provided are hydrogels comprising one or more macromers crosslinked to a mixture of peptides, wherein all or a portion of the peptides in the mixture comprise a recognition motif cleavable by a transpeptidase (e.g., sortase).

The present invention provides a polyethylene glycol derivative comprising a repeat unit having the structure of Formula (I) and a terminal group having the structure of Formula (II). The polyethylene glycol derivative provided by the present invention has good biocompatibility, due to the repeat unit having the structure of Formula (I); and can react with various groups such as amino, (acyl)hydrazino, and aminooxy with a fast reaction rate under mild reaction conditions, due to the o-phthalaldehyde terminal group having the structure of Formula (II). The polyethylene glycol derivative provided by the present invention is mixed with polyethylene glycol having an amino-containing terminal group in an aqueous medium, to rapidly form a chemically cross-linked hydrogel material. The hydrogel material has mild preparation conditions, fast gel-forming speed, high mechanical strength, and good stability. This polyethylene glycol hydrogel can be applied as drug sustained-release carrier, tissue engineering scaffold, etc. in the field of biomedical materials.

A hydrophilic polymer derivative having a cyclic benzylidene acetal linker represented by the following formula (1): ##STR00001##
wherein R.sup.1 and R.sup.6 are each independently a hydrogen atom or a hydrocarbon group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; X.sup.1 is a chemically reactive functional group; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 8; and Z.sup.1 and Z.sup.2 are each independently a selected divalent spacer.

A multi-arm, degradable polyethylene glycol derivative with a high molecular weight that does not cause vacuolation of cells is provided. A degradable polyethylene glycol derivative represented by the following formula (1):

##STR00001##

wherein n1 and n2 are each independently 45-950, W.sup.1 and W.sup.2 are each independently an oligopeptide of 2-47 residues, a1 and a2 are each independently 1-8, Q is a hydrocarbon chain having 2-12 carbon atoms and optionally containing an oxygen atom and/or a nitrogen atom, X.sup.1 and X.sup.2 are each independently a functional group capable of reacting with a bio-related substance, and L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are each independently a divalent spacer.

Polyurethane foams are made by curing a reaction mixture that contains an aromatic polyisocyanate, at least one isocyanate-reactive material having an average functionality of at least 2 and an equivalent weight of at least 200 per isocyanate-reactive group, at least one blowing agent, at least one surfactant and at least one catalyst, and a certain 3-oxopropanamide compound. Foams so produced emit low levels of aldehydes.

A heterobifunctional monodisperse polyethylene glycol with two adjacent monodisperse polyethylene glycol side chains, in which a peptide linker is degraded by intracellular enzymes to release a drug slowly and effectively mask the hydrophobicity of the drug, and an antibody-drug conjugate in which the antibody and the drug are bound using same is provided. A heterobifunctional monodisperse polyethylene glycol represented by the formula (1):

##STR00001##

wherein each symbol in the formula (1) is as defined in the DESCRIPTION.

A branched type hetero monodispersed polyethylene glycol represented by formula (1) ##STR00001##
where X.sup.1, Y.sup.1, n, E, L.sup.1, L.sup.2 and L.sup.3 are as defined herein.

The present invention relates to a polyethylene glycol conjugate medicament, a preparation method therefor and use thereof, and in particular relates to a polyethylene glycol conjugate medicament represented by formula (I) or a pharmaceutically acceptable salt thereof. The present invention also relates to a method for preparing the polyethylene glycol conjugate medicament or a pharmaceutically acceptable salt thereof, and an intermediate of the same, a pharmaceutical composition comprising the polyethylene glycol conjugate medicament or a pharmaceutically acceptable salt thereof, and use thereof in preparing a medicament.

##STR00001##

The present disclosure provides, among other things, a lipid nanoparticle adjuvant composition. The present disclosure provides pharmaceutical compositions that include a stable lipid nanoparticle adjuvant and human papillomavirus (HPV) virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.

The present disclosure provides conjugates comprising a Factor VIII moiety covalently attached via an oxime-containing linkage to a water-soluble polymer, such as for example, a polyethylene glycol polymer. Methods for preparing and for administering such conjugates, are also provided, as are water-soluble polymer oxyamine reagents useful for preparing the subject conjugates, among other things.