Cellink Bioprinting Ab

Cellink Ab

Cellheal As

Advanced Polymer Technology Ab

Ocean Tunicell As

Paul Gatenholm

Erik Gatenholm

Erdem Karabulut

Hector Martinez

Ivan Tournier

Michela Schettino

The present invention relates to preparation and use of biocompatible and electrically conductive 3D hydrogels comprising nanocellulose fibrils, such as disintegrated bacterial nanocellulose, plant derived nanocellulose, tunicate derived nanocellulose, or algae derived nanocellulose, together with carbon nanotubes or graphene oxide, as a biocompatible and conductive 3D hydrogel for diagnostics and intervention to mimic or restore tissue and organ function. Biocompatible conductive 3D hydrogels described in this invention can be extruded, casted or injected. The 3D hydrogels described in this invention are cohesive 3D structures and provide electrical conductivity in wet form. 3D hydrogels described in this invention can be further crosslinked using divalent ions such as Calcium ions which improve mechanical stability. Such crosslinking can take place in an animal or human body in a physiological environment after injection into the tissue. 3D hydrogels are biocompatible and show preferable mechanical properties and electrical conductivity through printed lines (4.10S cm). The 3D hydrogels prepared by this invention are suited as bioassays to screen drugs against neurodegenerative diseases such as Alzheimer's and Parkinson's, study brain function, and/or be used to link the human brain with electronic and/or communication devices. They can also be injected to replace neural tissue or stimulate guiding of neural cells. They can also be used to inject into the heart and stimulate the heart by using electrical signaling or to repair myocardial infarction.

Preparation and applications of biocompatible conductive 3D hydrogels based on cellulose nanofibrils for diagnostics and intervention of neurodegenerative and cardiac diseases

The present invention relates to preparation of bioink composed of cellulose nanofibril hydrogel with native or synthetic Calcium containing particles. The concentration of the calcium containing particles can be between 1% and 40% w/v. Such bioink can be 3D Bioprinted with or without human or animal cells. Coaxial needle can be used where cellulose nanofibril hydrogel filled with Calcium particles can be used as shell and another hydrogel based bioink mixed with cells can be used as core or opposite. Such 3D Bioprinted constructs exhibit high porosity due to shear thinning properties of cellulose nanofibrils which provides excellent printing fidelity. They also have excellent mechanical properties and are easily handled as large constructs for patient-specific bone cavities which need to be repaired. The porosity promotes vascularization which is crucial for oxygen and nutrient supply. The porosity also makes it possible for further recruitment of cells which accelerate bone healing process. Calcium containing particles can be isolated from autologous bone, allogenic bone or xenogeneic bone but can be also isolated from minerals or be prepared by synthesis. Preferable Calcium containing particles consist of &#x3b2;-tricalcium phosphate which is resorbable or natural bone powder, preferably of human or porcine origin. The particles described in the present invention have particle size smaller than 400 microns, or more preferably smaller than 200 microns, to make it possible to handle in printing nozzle without clogging and to obtain a good resolution. Cellulose nanofibrils can be produced by bacteria orbe isolated from plants. They can be neutral, charged or oxidized to be biodegradable. The bioink can be additionally supplemented by other biopolymers which provide crosslinking. Such biopolymers can be alginates, chitosans, modified hyaluronic acid or modified collagen derived biopolymers.

Preparation and applications of 3D bioprinting bioinks for repair of bone defects, based on cellulose nanofibrils hydrogels with natural or synthetic calcium phosphate particles

Clean chamber technology for 3D printers and bioprinters is described. An airtight chamber or enclosure is provided so that positive pressure can be created inside the chamber. Unfiltered air is sucked in from outside into the chamber through a high efficiency filter such as a HEPA filter, using an electrically powered fan or blower, filtering out at least about 99% of particles and contaminants. The filtered air is then pushed into a 3D printing area inside the chamber and out through vents within the frame of the chamber. The technology provides a clean environment for 3D bioprinting of human tissue models and organs and 3D cell culturing without requiring clean room facilities.

Clean chamber technology for 3D printers and bioprinters

The present invention relates to preparation and use of nanocellulose fibrils or crystals such as disintegrated bacterial nanocellulose, tunicate-derived nanocellulose, or plant-derived nanocellulose, together with carbon nanotubes, as a biocompatible and conductive ink for 3D printing of electrically conductive patterns. Biocompatible conductive bioinks described in this invention were printed in the form of connected lines onto wet or dried nanocellulose films, bacterial cellulose membrane, or tunicate decellularized tissue. The devices were biocompatible and showed excellent mechanical properties and good electrical conductivity through printed lines (3.8&#xb7;10S cm). Such scaffolds were used to culture neural cells. Neural cells attached selectively on the printed pattern and formed connective networks. The devices prepared by this invention are suited as bioassays to screen drugs against neurodegenerative diseases such as Alzheimer's and Parkinson's, study brain function, and/or be used to link the human brain with electronic and/or communication devices. They can also be implanted to replace neural tissue or stimulate guiding of neural cells. They can also be used to stimulate the heart by using electrical signaling or to repair myocardial infarction and/or damage related thereto.

Preparation and applications of biocompatible conductive inks based on cellulose nanofibrils for 3D printing of conductive biomedical devices and for use as models for study of neurodegenerative disorders and connection between brain/neurons and communication or other electronic devices

The present invention relates to biomaterial in the form of dispersion of cellulose nanofibrils with extraordinary shear thinning properties which can be converted into desire 3D shape using 3D Bioprinting technology. In this invention cellulose nanofibril dispersion, is processed through different mechanical, enzymatic and chemical steps to yield dispersion with desired morphological and rheological properties to be used as bioink in 3D Bioprinter. The processes are followed by purification, adjusting of osmolarity of the material and sterilization to yield biomaterial which has cytocompatibility and can be combined with living cells. Cellulose nanofibrils can be produced by microbial process but can also be isolated from plant secondary or primary cell wall, animals such as tunicates, algae and fungi. The present invention describes applications of this novel cellulose nanofibrillar bioink for 3D Bioprinting of tissue and organs with desired architecture.

Cellulose nanofibrillar bioink for 3D bioprinting for cell culturing, tissue engineering and regenerative medicine applications

Food, consumer, and industrial product packaging materials are provided by embodiments of the present invention. Films and laminates based on a combination of negatively charged polysaccharides are provided as such packaging materials. The films can be prepared by mildly treating soft wood with steam followed by alkali extraction and enzymatic treatment. Negatively charged non-cellulosic polysaccharides are isolated with weight average molecular weight Mw higher than 10,000 g/mol and molecular structure comprising a xylan main chain substituted with more than 15 molar % of glucuronic acid and more than 5 molar % arabinose. The negatively charged non-cellulosic polysaccharides can be casted from water solution on a suitable carrier and surface acetylated or coated with acetylated polysaccharide to obtain oxygen and water barrier packaging laminate. Inventive packaging materials can have strength at break above 55 MPa, elongation to break above 2.5%, cohesive and adhesive properties and good oxygen and moisture barrier properties.

Plasticizer-free flexible oxygen barrier films and laminates based on negatively charged and acetylated non-cellulosic polysaccharides isolated from biomass

Growing community of inventors

Riner, VA, United States of America

Paul Gatenholm