Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Cellular products or processes of preparing a cellular...
Reexamination Certificate
1999-04-16
2001-08-28
Foelak, Morton (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Cellular products or processes of preparing a cellular...
C521S064000, C424S043000, C424S078300, C424S426000, C424S428000
Reexamination Certificate
active
06281257
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to methods of synthesis for porous composite materials as well as the resulting porous composite materials as compositions suitable as a matrix for cellular infiltration and ingrowth, and in particular, the cultivation of cells within said matrix for the fabrication and repair of tissues and organs. In addition, said porous composite material has applications in chromatography, filtration, vibration absorption, insulation, and biodegradable packaging materials.
BACKGROUND
Transplantation is a life-saving therapy but is seriously limited by the scarcity of donor organs. In contrast to native tissue and organ transplantation from a non-autologous donor, tissues and organs generated through tissue engineering provide a more abundant alternative source for highly sought after biological materials. Scaffolding plays a pivotal role in the engineering of new tissues and organs. Various tissues have been engineered from highly porous scaffolds prepared from synthetic biodegradable polymers such as poly(glycolic acid), poly(lactic acid), and poly(glycolic acid-co-lactic acid). Alginic acid, a polysaccharide from seaweeds, is a family of natural copolymers of b-D-mannuronic acid and a-L-guluronic acid. Because of their biocompatibility, abundance in source, and low prices, they have been widely used in food industry as thickeners and emulsifying agents. They have also been processed into gel beads encapsulating living cells as an means of immunoprotection. However, alginate is difficult to work with because of its mechanical properties. What is needed is a matrix, readily fashioned into a given shape, having a desired porosity.
In addition, the passage of a fluidic mixture across a porous matrix facilitates the resolution of compounds contained within said mixture. Irregular pore size within a given matrix, however, can impair the separation of compounds of said mixture. What is needed is a matrix, readily fashioned into a given shape, having a desired porosity.
SUMMARY OF THE INVENTION
The present invention relates to methods of synthesis for porous composite materials as well as the resulting porous composite materials as compositions suitable as a matrix for cellular infiltration and ingrowth, and in particular, the cultivation of cells within said matrix for the fabrication and repair of tissues and organs. In one embodiment, the present invention contemplates a method wherein a matrix of a composite material comprising a desired porosity is used as a three dimensional structural template for in vitro tissue engineering applications. In another embodiment, the present invention contemplates a method wherein a matrix of an implantable composite material, comprising a desired porosity, is used as a three dimensional structural template facilitating the infiltration of cells in vivo. In addition, said porous composite material has applications in chromatography and filtration.
In a specific embodiment, the present invention contemplates a method comprising: a) providing: i) a polymer source, ii) an inorganic compound, and iii) a solvent; b) mixing said polymer with said solvent to create a homogenous polymer solution; c) adding said inorganic compound to said homogenous polymer solution to create a mixture; d) subjecting said mixture to such conditions whereby a solvent free matrix of a desired porosity (e.g. greater than approximately 80%, more preferably in greater than approximately 85%, still more preferably greater than approximately 90%, and most preferably greater than approximately 95%) is created. While the above-named components can be reacted in an alternative order, the above referenced reaction sequence has been found to produce the best results.
In a preferred embodiment, the present invention contemplates a method, comprising: a) providing: i) a polymer source, ii) an inorganic compound, and iii) a solvent; b) mixing said polymer with said solvent to create a polymer solution; c) adding said inorganic compound to said polymer solution to create a mixture; d) freezing said solvent in said mixture to create a frozen mixture; e) treating said frozen mixture (i.e. the mixture comprising frozen solvent) under conditions whereby a solvent free matrix is created having a porosity greater than approximately 80%. A variety of treatments in step e) are contemplated including but not limited to freeze drying to remove said solvent.
As noted above, the present invention specifically contemplates the resulting porous composite materials as compositions. In one embodiment, the present invention contemplates a composition comprising at least one polymer and at least one inorganic compound, said composition having a desired porosity (e.g. greater than approximately 80%, more preferably greater than approximately 85%, still more preferably greater than approximately 90%, and most preferably greater than approximately 95%).
In another embodiment, the present invention contemplates a method comprising: a) providing: i) a polymer source, ii) a solvent, and iii) a simulated body fluid; b) mixing said polymer with said solvent to create a homogenous polymer solution; c) subjecting said mixture to such conditions whereby a solvent free matrix of a desired porosity is created; d) contacting said solvent free matrix with said simulated body fluid.
In another embodiment, the present invention contemplates a method comprising: a) providing: i) a matrix of a desired porosity and ii) a simulated body fluid; and b) contacting said matrix with said simulated body fluid.
It is not intended the present invention be limited to a particular polymer or polymer source. The present invention contemplates homopolymers, copolymers and/or a mixture of polymers. In one embodiment, the polymer source is poly(L-lactic acid) (PLLA). In another embodiment, the polymer is poly(D,L-lactic acid-co-glycolic acid (PLGA). In another embodiment, the polymer is poly(methyl methacrylate) (PMMA). In another embodiment, the polymer is polystyrene (PS). These above referenced polymers are available from a variety of commercial vendors including Boehringer Ingelheim (Ingelheim, Germany) and from Medisorb Technologies International L. P. (Cincinnati, Ohio). Additionally, these polymers are used without further purification.
It is not intended the present invention be limited to a specific inorganic compounds used in the second phase of the above described methods. In one embodiment, the inorganic compound used is hydroxyapatite (HAP). In another embodiment, the inorganic compound is calcium phosphate (CAP). In another embodiment the inorganic compound is glass powder (GP).
Finally, it is also not intended that the present invention be limited to a specific solvent. In one embodiment the solvent is dioxane. In one embodiment the solvent is a mixture of dioxane and water. In another embodiment the solvent is benzene. In another embodiment the solvent is a mixture of benzene and chloroform.
The present invention also contemplates the use of a three dimensional matrix as a composition. Moreover, the present invention contemplates the using three dimensional matrices in combination with other components, such as cells. Where cells are used, it is not intended that the present invention be limited to a specific cell type (e.g. one cell type infiltrating a matrix). A variety of cell types (including mixtures of different cells) are contemplated. In one embodiment, the cells are osteoblasts. In another embodiment the cells are fibroblasts. In another embodiment the cells are epithelial. In another embodiment, the cells secrete a medically useful compound (e.g., hormone, cytokine, etc.). Such cells may be (but need not be) cells that have been manipulated by recombinant means to secrete such compounds.
The present invention contemplates methods wherein cells are added and grown in and on the matrix, as well as methods wherein the matrix is implanted (both with and without cells).
The present invention also contemplates methods wherein some of the matrices biodegrade, in vivo and in vit
Ma Peter X.
Zhang Ruiyun
Foelak Morton
Medlen & Carroll LLP
The Regents of the University of Michigan
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