Harvard College

Massachusetts Eye and Ear Infirmary

Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Mark Andrew Skylar-Scott

Jennifer Ann Lewis

David B Kolesky

Kimberly A Homan

Michael J McKenna

John Rosowski

Jochen Mueller

Aaron K Remenschneider

Daniel J Lee

Ryan L Truby

Katharina Theresa Kroll

Nicole Black

Alexander D Valentine

Edward Stuart Boyden

George M Church

Fei Chen

Adam H Marblestone

Ruixuan Gao

Patrick Lustenberger

Paul Warren Tillberg

Daniel Oran

Samuel Gordon Rodriques

Elliott Kozin

Sebastien G M Uzel

Amelia Sydney Gladman

Elliot Kozin

Alex H M Ng

Sebastien Uzel

Navin R Gupta

Michael T Valerius

Ryuji Morizane

Shoh Asano

Joseph Bonventre

Michael J Mckenna

Sebastien GM Uzel

Described are methods for producing tissue constructs, tissue constructs produced by the methods, and their use. The described method of producing a tissue construct comprises providing a granular tissue, depositing one or more filaments on or in the granular tissue, each filament comprising an ink, and gelling or fusing the granular tissue, thereby producing the tissue construct.

Tissue construct, methods of producing and using the same

Described are methods of enhancing development of renal organoids, methods of using the same, and kits.

Methods of enhancing development of renal organoids and methods of using the same

Described are methods for producing multi-layered tubular tissue structures, tissue structures produced by the methods, and their use.

Methods of producing multi-layered tubular tissue constructs

In one aspect, the present disclosure provides a nozzle for aD printing system. The nozzle may include a flowpath with a material inlet and a material outlet. The nozzle may further include a valve in fluid communication with the flowpath between the material inlet and the material outlet, where the valve includes a closed state and an open state, where in the closed state the valve obstructs the flowpath between the material inlet and the material outlet, and where in the open state the material inlet is in fluid communication with the material outlet. The nozzle may further include a compensator in fluid communication with the flowpath, where the compensator includes a contracted state associated with the open state of the valve and an expanded state associated with the closed state of the valve.

Valved nozzle with a compensator and massively parallel 3D printing system

This disclosure features artificial tympanic membrane graft devices and two-component bilayer graft devices that include a scaffold having a plurality of ribs made of a first material and a plurality of spaces between the ribs filled or made with the first material, a different, second material, a combination of the first and a second materials, or a combination of a second material and one or more other different materials. The bilayer graft devices have two components or layers. One component, e.g., the underlay graft device, can include a projection, and the second component, e.g., the overlay graft device, can include an opening that corresponds to the projection (or vice versa) so that the opening and the projection can secure the two layers together in a 'lock and key' manner. This disclosure also features methods of making, using, and implanting the three-dimensional artificial tympanic membrane and bilayer graft devices.

Artificial tympanic membrane devices and uses

Methods of tissue engineering, and more particularly methods and compositions for generating various vascularized 3D tissues, such as 3D vascularized embryoid bodies and organoids are described. Certain embodiments relate to a method of generating functional human tissue, the method comprising embedding an embryoid body or organoid in a tissue construct comprising a first vascular network and a second vascular network, each vascular network comprising one or more interconnected vascular channels; exposing the embryoid body or organoid to one or more biological agents, a biological agent gradient, a pressure, and/or an oxygen tension gradient, thereby inducing angiogenesis of capillary vessels to and/or from the embryoid body or organoid; and vascularizing the embryoid body or organoid, the capillary vessels connecting the first vascular network to the second vascular network, thereby creating a single vascular network and a perfusable tissue structure.

Methods of generating functional human tissue

The present invention enables three-dimensional nanofabrication by isotropic shrinking of patterned hydrogels. A hydrogel is first expanded, the rate of expansion being controlled by the concentration of the crosslinker. The hydrogel is then infused with a reactive group and patterned in three dimensions using a photon beam through a limited-diffraction microscope. Functional particles or materials are then deposited on the pattern. The hydrogel is then shrunk and cleaved from the pattern.

Three-dimensional nanofabrication by patterning of hydrogels

A present disclosure relates to a system for automatic design and manufacturing of 3D printing units and 3D products. The system is configured to obtain specification of a target structure corresponding to a 3D product; automatically determine a design and a printing path of a 3D printing unit based on the specification of the target structure, wherein the 3D printing unit is a micronozzle unit configured to print the target structure of the 3D product; automatically determine a manufacturing procedure to print the 3D printing unit based on the specification of the target structure; and instruct a 3D printer to print the 3D printing unit according to the manufacturing procedure and the printing path of the 3D printing unit.

Systems and methods for automated nozzle design and 3D printing

A 3D printed tubular construct, such as a nephron, with or without embedded vasculature as well as methods of printing tubular tissue constructs are described.

Tubular tissue construct and a method of printing

A printed tissue construct comprises one or more tissue patterns, where each tissue pattern comprises a plurality of viable cells of one or more predetermined cell types. A network of vascular channels interpenetrates the one or more tissue patterns. An extracellular matrix composition at least partially surrounds the one or more tissue patterns and the network of vascular channels. A method of printing a tissue construct with embedded vasculature comprises depositing one or more cell-laden filaments, each comprising a plurality of viable cells, on a substrate to form one or more tissue patterns. Each of the one or more tissue patterns comprises one or more predetermined cell types. One or more sacrificial filaments, each comprising a fugitive ink, are deposited on the substrate to form a vascular pattern interpenetrating the one or more tissue patterns. The vascular pattern and the one or more tissue patterns are at least partially surrounded with an extracellular matrix composition. The fugitive ink is then removed to create vascular channels in the extracellular matrix composition, thereby forming an interpenetrating vascular network in a tissue construct.

Method of printing a tissue construct with embedded vasculature

Growing community of inventors

Brookline, MA, United States of America

Mark Andrew Skylar-Scott