Semi-interpenetrating or interpenetrating polymer networks...

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert

Reexamination Certificate

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C424S425000, C424S486000, C525S903000, C525S937000

Reexamination Certificate

active

06224893

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention is generally in the area of using polymeric semi-interpenetrating and interpenetrating polymer network compositions and photocrosslinkable polymeric hydrogels in medical treatments, especially joint resurfacing and plastic surgery and delivery of drugs.
Congenital Defects
Many congenital defects, especially in the urogenital areas, require surgical correction. Examples include treatment of reflux and urinary incontinence. WO 94/25080 by Massachusetts Institute of Technology describes the use of injectable polysaccharide-cell compositions for delivering isolated cells by injection, which then form new tissue that is effective as a bulking agent. The polymers that are described crosslink ionically, as a function of ionic strength, temperature, pH, or combinations thereof. WO 96/40304 by Reprogenesis describes similar applications of polymeric hydrogels formed by covalent crosslinking, for example, by photopolymerization of the injected polymer-cell suspension using a catheter or during surgery.
Craniofacial Contour Deformities
Craniofacial contour deformities, whether traumatic, congenital, or aesthetic, currently require invasive surgical techniques for correction. Furthermore, deformities requiring augmentation often necessitate the use of alloplastic prostheses which suffer from problems of infection and extrusion. Correction of these defects and irregularities remain a difficult and controversial problem. Sims, et al., reported in
Plastic Reconstructive Surgery
98:845 (1996), the formation of new cartilage from injected polyethylene oxide-cell suspensions, and suggested that this technology would be useful in plastic surgery.
Replacement or Repair of Cartilaginous Surfaces
The aging population, especially of those active in sports and in jobs creating stress on joints, have little recourse at this time for repair or replacement of cartilage. Arthroscopic surgery can be used to remove torn cartilage but highly invasive and painful surgery is required for repair or replacement of a joint having little cartilage left. In most cases a prosthetic device must be used to replace the entire joint, following destruction of the smooth cartilaginous surface which normally allows for free movement of the abutting joint surfaces. As described in U.S. Pat. No. 5,514,378 to Vacanti, et al., it has been proposed to create new joint surfaces using a synthetic polymeric mesh seeded with chondrocytes, which forms new cartilage as the polymer degrades. Although this is promising, the seeded mesh must still be implanted surgically.
There is a need for improved injectable polymer-cell compositions which are biocompatible and biodegradable for delivering isolated cells by injection. There is a further need for less invasive means of covalently crosslinking polymer-cell suspensions following injection.
Accordingly, it is an object of the present invention to provide methods and compositions for injection of cells to form cellular tissues and cartilaginous structures, based on interpenetrating networks of synthetic polymers.
It is a further object of the invention to provide improved compositions to form cellular tissues and cartilaginous structures including non-cellular material which will degrade and be removed to leave tissue or cartilage that is histologically and chemically the same as naturally produced tissue or cartilage.
It is another object of the present invention to provide compositions for and a method for covalent crosslinking a polymer-cell suspension for formation of new tissue following injection.
SUMMARY OF THE INVENTION
Compositions for tissue engineering and drug delivery have been developed based on solutions of two or more polymers which form semi-interpenetrating or interpenetrating polymer networks upon exposure to active species following injection at a site in a patient in need thereof. The polymers crosslink to themselves but not to each other; semi-interpenetrating networks are formed when only one of the polymers crosslink. The resulting viscous solutions retain the biologically active molecules or cells at the site of injection until release or tissue formation, respectfully, occurs.
As a result of studies conducted with polymer-cell suspensions forming interpenetrating polymer networks, it has been determined that polymer solutions can be formulated wherein the active species is provided by exposure of the polymer solution to an exogenous source of active species, typically electromagnetic radiation, preferably light. Studies demonstrate that light will penetrate through skin, body fluids (such as synovial fluid) and membranes and polymerize the polymer solutions. The polymer solutions can be crosslinked ionically or covalently, to form a hydrogel, semi-interpenetrating polymer network or an interpenetrating polymer network.


REFERENCES:
patent: 5115020 (1992-05-01), Muramoto et al.
patent: 5334640 (1994-08-01), Desai et al.
patent: 5514378 (1996-05-01), Mikos et al.
patent: 5567435 (1996-10-01), Hubbell et al.
patent: 5700848 (1997-12-01), Soon-Shiong et al.
patent: 5709854 (1998-01-01), Griffith-Cima et al.
patent: 5837752 (1998-11-01), Shastri et al.
patent: 5900245 (1999-05-01), Sawhney et al.
patent: WO 93/17669 (1993-09-01), None
patent: WO 94/25080 (1994-11-01), None
patent: WO 96/40304 (1996-12-01), None
patent: WO 97/17038 (1997-05-01), None
Matsuda et al., “Photoinduced Prevention of Tissue Adhesion,”ASAIO Journal,38(1):M154-M157 (1992).
Sims et al., “Injectible Cartilage Using Polyethylene Oxide Polymer Substrates,”Plastic&Reconstructive Surgery,98(5):845-850 (1996).
Steinleitner et al., “An Evaluation of Flowgel* as an Intraperitoneal Barrier for Prevention of Postsurgical Adhesion Reformation,”Fertility and Sterility,57(2):305-308 (1992).
Steinleitner et al., “Poloxamer 407 as an Intraperitoneal Barrier Material for the Prevention of Postsurgical Adhesion Formation and Reformation in Rodent Models for Reproductive Surgery,”Obstetrics&Gynecology,77(1):48-52 (1991).

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