Medical University of South Carolina

Other

Mayo Foundation for Medical Education and Research

Esmaiel Jabbari

Michael J Yaszemski

Bradford Currier

Lichun Lu

Xun Zhu

Diederik H R Kempen

Bradford L Currier

Bradforf L Currier

Injectable compositions and use of the injectable compositions in tissue engineering applications are described. The injectable compositions are hydrogel-based compositions that can be crosslinked in situ following placement. The injectable compositions include microcapsules having predetermined erosion profiles that are loaded with nanogels having predetermined sustained release profiles for signaling molecules conjugated to the nanogels. Following crosslinking, the compositions are designed to sequentially release signaling molecules over a predetermined period of time with various release profiles. The compositions can carry additional components to stimulate tissue generation such as stem cells and extracellular matrix (ECM) components.

Drug conjugated nanogels in microcapsule for delayed sustained protein delivery

The present disclosure is directed to hybrid multifunctional macromers that can self-assemble to form nanoparticles for on-demand and targeted release of morphogens. Embodiments of the disclosure can include the hybrid multifunctional macromers and peptide sequences incorporated therein, self-assembled nanoparticles including the hybrid multifunctional macromers, methods for producing the hybrid multifunctional macromers and peptide sequences, and methods for treating a disease by the on-demand and targeted delivery of a compound using the hybrid multifunctional macromers.

Enzymatically cleavable self-assembled nanoparticles for morphogen delivery

Systems and methods for targeting specific cancer cell subpopulations present in tumor tissue are described. A system can include a first component for specifically targeting cancer stem cells and a second component for specifically targeting differentiated cancer cells. A system can include a drug conjugated to small (e.g., 5-20 nm) nanoparticles, e.g., polyhedral oligomeric silsesquioxane nanoparticles. The small nanoparticles can be preferentially taken up by cancer stem cells via macropinocytosis and can release a toxic payload within the cancer stem cells without triggering the efflux pump. A system can include a second component that targets differentiated cancer cells, e.g., a free drug or a drug encapsulated in nanoparticles.

Drug delivery method for targeting cancer stem cells

Compositions and implants for articular cartilage repair or regeneration are described. The compositions are hydrogel-based compositions that can incorporate signaling molecules for cartilage repair. The compositions include microcapsules having predetermined erosion profiles that are loaded with nanogels having predetermined sustained release profiles for signaling molecules conjugated to the nanogels. A plurality of compositions, each carrying different signaling molecules, can be layered to form a multi-layered implant, with each layer sequentially releasing the encapsulated signaling molecules over a predetermined period of time. The compositions can carry additional components to encourage tissue generation such as stem cells and extracellular matrix (ECM) components.

Compositions and layered structures formed therewith for regeneration of articular cartilage

Systems and methods for targeting specific cancer cell subpopulations present in tumor tissue are described. A system can include a first component for specifically targeting cancer stem cells and a second component for specifically targeting differentiated cancer cells. A system can include a drug conjugated to small (e.g., 5-20 nm) nanoparticles, e.g., polyhedral oligomeric silsequioxane nanoparticles. The small nanoparticles can be preferentially taken up by cancer stem cells via macropinocytosis and can release a toxic payload within the cancer stem cells without triggering the efflux pump. A system can include a second component that targets differentiated cancer cells, e.g., a free drug or a drug encapsulated in nanoparticles.

Drug delivery system and method for targeting cancer stem cells

A three-dimensional cell culture system that includes a keratin-based hydrogel precursor solution and a cell culture vessel is provided. The precursor solution includes solubilized keratin that has been functionalized to include a crosslinking moiety. The crosslinking moiety exhibits controllable crosslinking, e.g., a photopolymerizable crosslinking moiety. The crosslinking functionality is bonded to the keratin via cysteines following reduction of disulfide bonds of the native keratin. The precursor solution can be combined with cells to form a cell suspension that is disposed on a surface of the cell culture vessel. Alternatively, the cells can be added to a surface of a keratin-based hydrogel that has been formed on a surface of the cell culture vessel. The resulting three-dimensional cell culture system is a biomimetic/biologic, trypsin-degradable cell culture system for expansion of mammalian cells. The expanded cells are expected to possess a morphology similar to the primary cells prior to cultivation.

Keratin allyl thioether three-dimensional cell culture system

Keratin-based hydrogels and aqueous compositions and methods for forming the hydrogels and compositions are described. The compositions include solubilized keratin that has been functionalized to include a crosslinking moiety. The crosslinking moiety exhibits controllable crosslinking, e.g., a photopolymerizable crosslinking moiety. The crosslinking functionality is bonded to the keratin via cysteines following reduction of disulfide bonds of the native keratin. The compositions can be injectable and can include living cells and/or other biologically active agents, for instance for use in tissue regeneration.

Keratin-based hydrogels

Synthetic inert 3D gel culture systems are described that can be finely tuned to exhibit desired and predetermined physical, chemical, mechanical, and biochemical properties. The culture system can be utilized to study the effect of microenvironmental factors on cancer cell response, and in particular on cancer stem cell (CSC) response. Cancer cells can be encapsulated in a crosslinked gel system having a narrow range of predetermined gel stiffness. One or more biochemical factors including peptides that can affect the growth, development, and/or proliferation of CSCs can be incorporated in the system to examine the effects of the factor(s) on the encapsulated cells with regard to growth, proliferation, size, etc.

Three dimensional matrix for cancer stem cells

Bone tissue biomimetic materials, biomimetic constructs that can be formed with the materials, and methods for forming the materials and constructs are described. The bone tissue biomimetic materials include electrospun nanofibers formed of polymers that are conjugated with peptides that include acidic amino acid residues. The materials can incorporate high levels of mineralization so as to provide mechanical strength and promote osteogenesis and/or osteoconductivity on/in the bone tissue biomimetic materials. The materials and constructs can be utilized in forming tissue engineered structures for in vitro and in vivo use. Macroscopic bone tissue biomimetic scaffolds formed from the materials can be seeded with osteogenic cells and utilized to develop bone graft materials that can exhibit strength and osteoconductivity similar to the native bone and that exhibit uniform distribution of nutrients in the scaffolds.

Biomineralization promoting materials and methods of forming same

Bone tissue biomimetic materials

Bioresorbable compositions for treating skeletal tissue are disclosed. The biomedical compositions are formed from a polylactide polymer, a polyglycolide polymer, or a poly(lactic-co-glycolic acid) polymer having a relatively low molecular weight. For instance, the average number molecular weight of the polymer is generally less than 10,000, such as from about 500 to about 5,000. Fumarate groups are incorporated into the low molecular weight polymer that provide crosslinking sites. If desired, ethyl-lene oxide groups and ceramic particles may also be incorporated into the polymer for producing compositions having a variety of properties. For example, the biomedical composition of the present disclosure can be used to treat soft skeletal tissue or to treat hard skeletal tissue. The biomedical compositions are biodegradable and can contain various therapeutic, beneficial and pharmaceutical agents that may be released during degradation of the polymer.

Bioresorbable composite for repairing skeletal tissue

A composition is disclosed which comprises (i) a macromer prepared by reacting an unsaturated diacid having a carbon-carbon double bond and a saturated diacid, and (ii) a bioactive ceramic grafted to the macromer. In one embodiment, the unsaturated diacid having a carbon-carbon double bond is fumaric acid, the saturated diacid is compatible with fumaric acid and poly(propylene fumarate) such as succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid and mixtures thereof, and the bioactive ceramic is hydroxyapatite. In another embodiment, hydroxyapatite is grafted with a biodegradable and crosslinkable macromer comprising silane units alternating with furnarate and adipate units.

Growing community of inventors

Columbia, SC, United States of America

Esmaiel Jabbari