Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Cambridge Enterprise Limited

Integra Lifesciences Corporation

Shriners Hospitals for Crippled Children

The Shriner's Hospital for Crippled Children

Ioannis V Yannas

John F Burke

Dennis Paul Orgill

James F Kirk

Chor Huang

Carolyn C Compton

Scott Ritterbush

Charles E Butler

Mark Barlow

Philip L Gordon

Andrew Lynn

Borivoje B Mikic

Howard M Loree, Ii

Brendan A Harley

William Bonfield

Lorna J Gibson

Albert S Chang

Frederick H Silver

Christian Krarup

David L Sieverding

Thorkild V Norregaard

Martin J Forbes

Eugene M Skrabut

Zachary D Wissner-Gross

Ariel Ferdman

Peter J Stasikelis

Elaine Lee

A process for the preparation of a composite biomaterial comprising: providing a first substantially solid component comprising one or more of collagen, a glycosaminoglycan, albumin, hyaluronan, chitosan, and synthetic polypeptides comprising a portion of the polypeptide sequence of collagen, and optionally an inorganic material, said component having at least a surface portion that is porous; providing a fluid composition comprising one or more of collagen, a glycosaminoglycan, albumin, hyaluronan, chitosan, and synthetic polypeptides comprising a portion of the polypeptide sequence of collagen, and a liquid carrier, and optionally an inorganic material; contacting said fluid composition with said porous surface portion of said first component; cooling said fluid composition to a temperature at which the liquid carrier transforms into a plurality of solid crystals or particles; removing at least some of the plurality of solid crystals or particles by sublimation and/or evaporation.

Biomaterial

The present invention relates to a method of skin regeneration of a wound or burn in an animal or human. This method comprises the steps of initially covering the wound with a collagen glycosaminoglycan matrix, allowing infiltration of the grafted GC matrix by mesenchymal cells and blood vessels from healthy underlying tissue and applying a cultured epithelial autograft sheet grown from epidermal cells taken from the animal or human at a wound free site on the animal's or human's body surface. The resulting graft has excellent take rates and has the appearance, growth, maturation and differentiation of normal skin.

Method of skin regeneration using a collagen-glycosaminoglycan matrix

A method for producing a biodegradable polymer having a preferentially oriented pore structure and a method for using the polymer to regenerate damaged nerve tissue is disclosed. The preferentially oriented pores are produced by an axial freezing process and serve to promote proper vascularation and regeneration of the damaged nerve. Preferably, the biodegradable polymer comprises uncrosslinked collagen-glycosaminoglycan.

Prosthesis for promotion of nerve regeneration

This invention relates to porous, biodegradable materials in which the pore size, biodegradation rate, and pore volume fraction are controlled and within values at which skin contraction rates around an implant-containing wound are delayed or slowed.

Biodegradable templates for the regeneration of tissues

Process for forming a multilayer blood vessel prosthesis. Each layer is formed from bioreplaceable materials which include those produced by contacting collagen with an aminopolysaccharide and subsequently covalently crosslinking the resluting polymer, polymers of hydroxyacetic acid and the like. Cross flow filtration molding and wet extrusion molding are two processes which are particularly useful for forming the inner layer of the blood vessel prosthesis. The outer layer of the blood vessel prosthesis is preferably formed by freeze drying a dispersion of the bioreplaceable material onto the inner layer(s). The disclosed blood vessel prosthesis is a multilayer structure with each layer having a porosity and other physicochemical and mechanical characteristics selected to maximize the effectiveness of the blood vessel. The prosthesis funcitons initially as a thromboresistant conduit with mechanical properties which match those of the adjacent natural blood vessel. Eventually, the prosthesis functions as a regeneration template which is replaced by new connective tissue that forms during the healing process following attachment of the prosthesis.

Multilayer bioreplaceable blood vessel prosthesis

Process for forming a multilayer blood vessel prosthesis. Each layer is formed from bioreplaceable materials which include those produced by contacting collagen with an aminopolysaccharide and subsequently covalently crosslinking the resulting polymer, polymers of hydroxyacetic acid and the like. Cross flow filtration molding and wet extrusion molding are two processes which are particularly useful for forming the inner layer of the blood vessel prosthesis. The outer layer of the blood vessel prosthesis is preferably formed by freeze drying a dispersion of the bioreplaceable material onto the inner layer(s). The disclosed blood vessel prosthesis is a multilayer structure with each layer having a porosity and other physicochemical and mechanical characteristics selected to maximize the effectiveness of the blood vessel. The prosthesis functions initially as a thromboresistant conduit with mechanical properties which match those of the adjacent natural blood vessel. Eventually, the prosthesis functions as a regeneration template which is replaced by new connective tissue that forms during the healing process following attachment of the prosthesis.

Process for forming multilayer bioreplaceable blood vessel prosthesis

A method for preserving the porosity of porous materials is disclosed. In this method, the porous material is subjected to elevated temperature and vacuum conditions to thereby produce a dimensionally-stable, non-collapsible porous material.

Method for preserving porosity in porous materials

This invention relates to the introduction of viable cells into a fibrous lattice by surgical, force-utilizing, or other manipulative techniques, all of which are referred to herein as 'seeding.' One embodiment comprises an autografting technique which involves intact tissue. Other embodiments which involve the distribution of an aqueous suspension of cells comprise centrifugal, spraying, pipetting and syringe emplacement. Each cell that survives the seeding process may reproduce into a colony of cells which grow until they reach confluence, thereby creating a uniform layer or volume of tissue. By proper placement of cells capable of generating such colonies, the period of recovery of a wound may be drastically reduced. In addition, research by the Applicants indicates that tissue that is regenerated using the methods of this invention to seed a lattice comprising collagen and glycosaminoglycan tends to be smoother, more uniform, less fibrotic, less scarred and more flexible than tissue that is regenerated by wound contraction or conventional autografting.

Method of using a fibrous lattice

Cell-seeding procedures involving fibrous lattices

A process for preparing a crosslinked collagen-glycosaminoglycan composite material which comprises forming an uncrosslinked composite material from collagen and a glycosaminoglycan and contacting the uncrosslinked composite with a gaseous aldehyde until a crosslinked product having an M.sub.c of from about 800 to about 60,000 is disclosed along with composite materials prepared by this process. Artificial skin produced by this process is more stable toward long-term storage than similar materials prepared using other methods of crosslinking.

Method for the preparation of collagen-glycosaminoglycan composite

This invention comprises the use of centrifugal force to introduce viable cells into a fibrous lattice, as well as fibrous lattices that are seeded with cells by the use of centrifugal force. A variety of fibrous lattices may be seeded by the methods of this invention, such as a highly porous lattice comprising collagen fibers crosslinked with glycosaminoglycan. Before the centrifugation, a piece of intact tissue is harvested from a donor site. It is treated with one or more substances, such as trypsin or collagenase, to dissociate cells from the tissue. The cells are then mixed with an aqueous solution to create an aqueous suspension of cells. A piece of fibrous lattice is placed within a container, referred to herein as a 'bucket,' that is suitable for rotation by a centrifuge. The aqueous suspension of cells is placed within the bucket, in contact with the lattice. The centrifuge is then rotated. Centrifugal force causes the cells, which are denser than the aqueous solution, to be forced into the lattice in a relatively uniform distribution. By controlling various parameters, cells can be seeded into any desired location within a lattice.

Method of promoting the regeneration of tissue at a wound

This invention relates to crosslinked collagen and glycosaminoglycan materials, and to procedures for preparing such materials. It has been discovered that if collagen fibrils in an aqueous acidic solution are contacted with a crosslinking agent before being contacted with glycosaminoglycan, the materials produced have extremely low levels of thrombogenicity. Such materials are well suited for in-dwelling catheters, blood vessel grafts, and other devices that are in continuous contact with blood for long periods of time.

Procedures for preparing composite materials from collagen and

Composite materials are disclosed which are formed by contacting collagen with a mucopolysaccharide and subsequently covalently crosslinking the resultant polymer. These composite materials have a balance of mechanical, chemical and physiological properties which make them useful in surgical sutures and prostheses of controlled biodegradability (resorption) and controlled ability to prevent development of a foreign body reaction, and many are also useful in applications in which blood compatibility is required.

Crosslinked collagen-mucopolysaccharide composite materials

A cross flow filtration molding apparatus and method are disclosed which are particularly useful for forming complicated shapes from dispersions of particles in a liquid medium. Dispersion is pumped through a mold which has porous walls and a sufficient pressure differential is applied to drive a portion of the liquid medium through the porous walls which results in deposition of particles on the walls to form a shaped article. The shaped article may inherently have sufficient structural integrity, or it may be post-treated to provide additional structural integrity.

Growing community of inventors

Newton Center, MA, United States of America

Ioannis V Yannas