In some aspects, methods and probiotic compositions are provided for the treatment of bone diseases such as, e.g., ostetoporosis. In some embodiments, one or more bacteria from the warm microbiota such as, e.g., Clostridialeace-assimilate, Lactobacillus, Bifidobacteriaceae, Akkermansia, and/or Parabacteroides may be administered to a subject, such as a human subject, to treat the bone disease. In some embodiments, heat may be applied to the subject to promote the development of warm microbiota to treat the bone disease.

A drug-polymer conjugate, which is a copolymer of at least one monomer of formula (I) where: X may be the same or different at each occurrence and represents a terminal functional group comprising an alkyne or an azide; Q is independently selected at each occurrence and may be present or absent and when present, represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon, optionally substituted aryl and optionally substituted heteroaryl; D is a releasable bicyclic prostaglandin; L is a linker group; and at least one co-monomer of Formula III J-(Y.sup.1-A).sub.n, J represents a linking functional group, n is 2 to 8 preferably 3 to 8; Y.sup.1 comprises a polyether of formula (OR.sup.a).sub.m wherein R.sup.a is independently ethylene, propylene and butylene and m is from 1 to 300 (preferably 2 to 300) and the polyether is in chain with one or more groups which are preferably selected from one or more of optionally substituted straight or branched C.sub.1 to C.sub.10 alkylene, amino, ether, ester, amide, carbonate and carbamate; A may be the same or different at each occurrence and represents a group comprising a terminal functional group comprising an alkyne or an azide functionality, wherein said terminal functional group is complementary to the terminal functional group X of formula (I) providing triazole moieties from reaction of X and A.

The invention provides novel compounds and polymers, degradable hydrogel compositions, medical devices and implants, as well as methods thereof, that allow on-demand release and controlled delivery of antimicrobial agents.

The present invention provides refillable drug delivery systems, as well as methods of refilling the systems, and methods of using them to treat diseases.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

The invention relates to a hydrogel matrix comprising a mixture of a covalent peptide-polymer conjugate and an oligosaccharide; wherein the oligosaccharide is a highly negatively charged sulfated oligosaccharide selected from the group consisting of heparin, dextran sulfate, α-cyclodextrin sulfate, β-cyclodextrin sulfate and γ-cyclodextrin sulfate; wherein said polymer comprised in said peptide-polymer conjugate is a linear or multi-arm polyethylene glycol; wherein said peptide comprised in said peptide-polymer conjugate is a peptide, which consists of an amino acid sequence selected from the group consisting of SEQ ID NO.4, SEQ ID NO.5, SEQ ID NO. 18 and SEQ ID NO. 19; and wherein said hydrogel matrix is configured in the form of an oligosaccharide/peptide/polymer system, in which said peptide is chemically conjugated to the polymer such that the hydrogel is obtained by mixing the peptide-polymer conjugate and the oligosaccharide.

The invention provides injectable, tough hydrogels that can be crosslinked in situ on demand using minimally-invasive methods, such as visible light exposure is an unmet medical challenge. Among the emerging biopolymers for tissue sealing, gelatin methacryloyl (GelMA), a naturally-derived biopolymer obtained from denatured collagen, has secured a promising role as a result of its excellent bioadhesion, biodegradation, and biocompatibility. To overcome one of the main shortcomings of GelMA, i.e., brittleness, we hybridized it using methacrylate-modified alginate (AlgMA) to impart ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid GelMA-AlgMA hydrogels provide a photocrosslinkable, injectable, and adhesive platform with an excellent toughness that can be engineered using divalent cations, such as calcium. This class of novel hybrid biopolymers with more than 600% improved toughness may set the stage for durable, mechanically-resilient, and cost-effective tissue sealants in minimally invasive procedure, especially for stretchable tissues.

The present invention relates to a tyrosine kinase inhibitor (“TKI”) conjugate or a pharmaceutically acceptable salt thereof, wherein said conjugate comprises a plurality of TKI moieties -D covalently conjugated via at least one moiety -L.sup.1-L.sup.2- to a polymeric moiety Z, wherein -L.sup.1- is covalently and reversibly conjugated to -D and -L.sup.2- is covalently conjugated to Z and wherein -L.sup.1- is a linker moiety and -L.sup.2- is a chemical bond or a spacer moiety; and to related aspects.

The present disclosure is in the field of gastric resident systems. A device for extended retention in a stomach is provided. The device includes: first, second, and third arms, the second and third arms being connected to respective ends of the first arm. The device is configured to transform between a compressed configuration and an expanded configuration. The device further includes a biasing member configured to bias the device into the expanded configuration whereby the second and third arms are configured to mechanically engage each other to retain the system in the expanded configuration.

A compound includes a polysaccharide moiety and one or more chelating agents. The one or more chelating agents are covalently bonded to the polysaccharide moiety. The polysaccharide moiety can include a glycosaminoglycan moiety, such as a hyaluronic acid polymer or a sulfated glycosaminoglycan moiety. The compound can be used to treat or prevent a disease or disorder in a patient with a metal implant. The compound reduces a concentration of metal particulates or metal ions in the subject.