Abstract: The present disclosure provides transparent, elastic silk hydrogels for applications, including corneal reshaping to restore visual acuity and photolithography. The present disclosure also provides methods of photocrosslinking silk fibroin protein using riboflavin as a photoinitiator and exposing such riboflavin doped silk fibroin to light resulting in the formation of a transparent, elastic hydrogel.

Abstract: The present invention provides, among other things, methods for producing platelets including the steps of providing a silk membrane about 2 ?m and 100 ?m thick, inclusive, contacting the silk membrane with a porogen to form a porous silk membrane comprising at least one silk wall defining a lumen, associating the porous silk membrane with stromal derived factor-1? and at least one functionalizing agent, forming a three dimensional silk matrix comprising interconnected pores wherein the pores have a diameter of between about 5 and 500 ?m, inclusive, wherein the silk matrix is formed around at least a portion of the porous silk membrane, introducing a plurality of megakaryocytes to the silk matrix such that the megakaryocytes are located at least partially within the porous silk matrix, and stimulating the plurality of megakaryocytes to produce platelets. Also provided are various new compositions and methods of making those compositions.

Abstract: The present disclosure relates to cultured tissue, methods for production of the cultured tissue, and a bioreactor system for production of the cultured tissue. In some embodiments, the production of the cultured tissue may involve, at a first bioreactor, feeding a fiber scaffold into a chamber containing culture media, seeding the chamber with precursor cells, and allowing the precursor cells to proliferate and differentiate on a surface of the fiber scaffold. At downstream bioreactors, the production of the cultured tissue may further involve twisting a plurality of the cell-laden fibers to provide a cell-laden yarn, and weaving or knitting the cell-laden yarn into a three-dimensional (3D) structure. In some embodiments, the cultured tissue may be whole muscle cultured meat composed of muscle cell-laden fibers and fat cell-laden fibers. The whole muscle cultured meat may have a structural organization and hierarchy that mimics natural skeletal muscle tissue.

Abstract: The present disclosure relates to cultured tissue, methods for production of the cultured tissue, and a bioreactor system for production of the cultured tissue. In some embodiments, the production of the cultured tissue may involve, at a first bioreactor, feeding a fiber scaffold into a chamber containing culture media, seeding the chamber with precursor cells, and allowing the precursor cells to proliferate and differentiate on a surface of the fiber scaffold. At downstream bioreactors, the production of the cultured tissue may further involve twisting a plurality of the cell-laden fibers to provide a cell-laden yarn, and weaving or knitting the cell-laden yarn into a three-dimensional (3D) structure. In some embodiments, the cultured tissue may be whole muscle cultured meat composed of muscle cell-laden fibers and fat cell-laden fibers. The whole muscle cultured meat may have a structural organization and hierarchy that mimics natural skeletal muscle tissue.

Abstract: The inventions provided herein relate to compositions, methods, delivery devices and kits for repairing or augmenting a tissue in a subject. The compositions described herein can be injectable such that they can be placed in a tissue to be treated with a minimally-invasive procedure (e.g., by injection). In some embodiments, the composition described herein comprises a compressed silk fibroin matrix, which can expand upon injection into the tissue and retain its original expanded volume within the tissue for a period of time. The compositions can be used as a filler to replace a tissue void, e.g., for tissue repair and/or augmentation, or as a scaffold to support tissue regeneration and/or reconstruction. In some embodiments, the compositions described herein can be used for soft tissue repair or augmentation.

Abstract: The present invention, in some aspects, provides compositions including a solution comprising a plurality of exfoliated silk microfibrils and/or exfoliated silk nanofibrils, wherein the micro- or nano-fibrils are characterized as having a substantially nematic structure, as well as methods for making and using the same.

Abstract: The present disclosure relates to compositions, methods of making, and methods of using a modified silk-based composition having a selectively tunable hydrophobicity. The provided compositions include silk fibroin having a haloalkyl substituent. The haloalkyl substituent is coupled to an amino acid of the silk fibroin though a linking agent.

Abstract: A method of forming a tissue. The method includes providing a source of a pre-tissue composition comprising endothelial cells. The method also includes perfusing a culture media into the pre-tissue composition using a plurality of primary channels and a plurality of secondary channels to form the tissue, wherein the endothelial cells are configured to form the secondary channels via vasculogenesis.

Abstract: Provided herein relates to methods and compositions for preparing a silk microsphere and the resulting silk microsphere. In some embodiments, the methods and compositions described herein are all aqueous, which can be used for encapsulating an active agent in a silk microsphere, while maintaining activity of the active agent during processing. In some embodiments, the resulting silk microsphere can be used for sustained delivery of an active agent encapsulated therein.

Abstract: Disclosed are apparatus, compositions, and methods for promoting regeneration of tissue on a subject such as a wounded, damaged, or injured appendage, or within a subject such as a wounded, damaged, or injured organ. The disclosed apparatus, composition, and methods include or utilize wearable sleeves and regenerative compositions.

Abstract: Systems and methods for predicting patient-specific responses to the administration of medicaments that are indicated to modulate megakaryocyte differentiation, proplatelet formation, and/or platelet production are disclosed. The systems and methods can include a three-dimensional bone marrow model that is composed of silk fibroin sponges including a protein of the extracellular matrix, such as fibrinogen. The methods include creating patient-specific megakaryocyte progenitors (or progenitors thereof), seeding those progenitors into the model, introducing the medicament to the progenitors within one model, perfusing the model with a cell culture medium, maturing the progenitors, comparing platelet generation from the model including the medicament to a control model, and generating a report having a prediction of in vivo efficacy based on the comparison.

Abstract: The present disclosure provides a method for screening drug delivery vehicles for use in delivering cargo via oral delivery. The method includes introducing a drug delivery vehicle comprising an imaging agent into a lumen of an artificial intestine system composed of a scaffold matrix material. The scaffold matrix material includes an interconnected network of pores, intestinal epithelial cells positioned on an inner surface of the lumen, and human-based cells positioned within the pores and surrounding the intestinal epithelial cells. The method includes maintaining the artificial intestine system in physiologically relevant conditions for a predetermined length of time, and detecting a color change induced by the imaging agent within at least a portion of the human-based cells.

Abstract: Provided herein are genetically engineered mammalian cells that endogenously express one or more phytochemicals, vitamins, or therapeutic agents and suitable for use in a cultured meat product. Methods of making and using the genetically engineered mammalian cells and the cultured meat products are also provided.

Abstract: The present disclosure provides certain silk-fibroin compositions with particular characteristics and/or properties. In some embodiments, the disclosure provides low molecular weight compositions. In some embodiments, the disclosure provides silk fibroin compositions that comprise an active (e.g., a biological) agent or component. In some embodiments, the disclosure provides low molecular weight silk fibroin compositions that comprise an active (e.g., a biological) agent or component. In some embodiments, an active agent is stabilized in a silk composition, e.g., for a period of time and/or against certain conditions or events. In some embodiments, a component present in a silk fibroin composition may be subject to analysis and/or characterization. In some embodiments, a component present in a silk fibroin composition may be recovered from the composition.

Abstract: A method of making silk articles including preparing a silk fibroin solution including silk fibroin and microalgae, and introducing the silk fibroin solution into a solvent bath including a crosslinking agent. The method can incorporate 3D printing techniques to allow for easy fabrication of the articles into various forms. The silk articles can provide a cell-friendly matrix that allows 3D encapsulation of microalgae while maintaining normal cell proliferation and functions for an extended period of time.

Abstract: The present disclosure relates to biocompatible injectable compositions. The provided compositions comprise or consist of silk fibroin, hyaluronic acid, horseradish peroxidase, hydrogen peroxide, and water. The injectable composition is tunable and may be adapted to have a gelation time from 3 minutes to 20 minutes, a storage modulus of 6 Pa to 4000 Pa, be injectable through a needle having a size from 32 G to 18 G, have optical transmittance from 75% to 95% for at least one wavelength from 400 nm to 700 nm, have a volume expansion from 5% to 400% relative to an original volume of the hydrogel after soaking in an aqueous solution for 12 hours, and/or have a hydrogel stability by maintaining at least 75% of the storage modulus and the optical transmittance of the hydrogel after 6 months in vivo. The present disclosure provides methods for making and using the same.

Abstract: A method of making drug-eluting regenerated silk fibroin particles using cryogranulation. The method has a first step of injecting a mixture into a super-cooled fluid, the mixture including regenerated silk fibroin and at least one medicament. A second step of incubating the drug-eluting particles in the super-cooled fluid to promote cryogelation may also be used. The size distribution, morphology, and cross-linking efficiency of the particles can depend on several controllable variable, such as starting concentrations of cross-linking agents and silk fibroin in the mixture, the injection pressure, and the temperature of the super-cooled fluid.

Abstract: The present invention provides, in some embodiments, multi-layer silk compositions including a first layer comprising silk fibroin and keratinocytes, a second layer comprising silk fibroin and fibroblasts, a third layer comprising silk fibroin and adipocytes, and a plurality of nervous system cells, wherein at least some of the plurality of nervous system cells span at least two layers, and methods of making and using the same. In some embodiments, provided methods and compositions further include immune cells and/or endothelial cells.

Abstract: Provided herein is a cultured meat product comprising a confluent serum-free insect muscle cell culture seeded on a food safe substrate. Further provided herein is a method for producing a cultured meat product comprising the steps of: culturing insect muscle cells on a food safe substrate in serum-free culture medium for a time sufficient for the cells to reach confluence. Also provided herein is a bioactuator comprising confluent insect muscle cells cultured in a flexible substrate to form muscle fibers.

Abstract: Provided herein relates to implantable devices and systems with dynamic silk coatings. In some embodiments, the dynamic silk coatings can be formed in situ or in vivo.