POROUS BIOABSORBABLE IMPLANT

Abstract

A method for forming a porous implant suitable for a cavity from which tissue has been removed includes incorporating a gas or a pore forming agent into an alginate solution; transferring the alginate solution with the gas or the pore forming agent into a solidified body mold having a desired shape with an outer surface; removing the water from the solidified body; and subjecting the solidified body to a conversion solution to convert the outer surface to a less soluble alginate creating a composition comprising the outer surface having less soluble alginate and a core having more soluble alginate.

Claims

1-22. (canceled)

23. A method for forming a porous implant suitable for a cavity from which tissue has been removed, comprising: a. incorporating a gas or a pore forming agent into an alginate solution; b. transferring the alginate solution with the gas or the pore forming agent into a solidified body mold having a desired shape with an outer surface; c. removing the water from the solidified body; and d. subjecting the solidified body to a conversion solution to convert the outer surface to a less soluble alginate creating a composition comprising the outer surface having the less soluble alginate and a core having a more soluble alginate.

24. The method of claim 23, comprising inserting an orientation marker into the body, the orientation marker being spaced inwardly from exterior margins of the implant.

25. The method of claim 23, comprising inserting a plurality of radiopaque elements in an orientation lying in a plane into the body.

26. The method of claim 23, wherein the water removing step comprises freeze drying.

27. The method of claim 23, wherein the more soluble alginate is sodium alginate.

28. The method of claim 27, wherein the less soluble alginate is calcium alginate.

29. The method of claim 28, further comprising incorporating a starch in finely divided particulate form into the alginate solution so that when the calcium alginate is formed, it precipitates about the starch particles to minimize shrinkage of the solidified body during the conversion of sodium alginate to calcium alginate.

30. The method of claim 29, wherein the starch degrades quickly within the body cavity in the presence of body fluid, and wherein the calcium alginate at a surface region degrades to open up the incorporated starch particles to degradation which provides an evolving porosity.

31. The method of claim 23, wherein the act of subjecting comprises dipping the solidified body into the conversion solution.

32. The method of claim 23, comprising sizing and shaping the porous implant so as to fit within the cavity and to conform the tissue lining of the cavity about the porous implant.

33. The method of claim 23, wherein the alginate solution includes a radiopaque imaging agent.

34. A method for forming a porous implant suitable for a cavity from which tissue has been removed, comprising: a. preparing an alginate solution; b. incorporating a gas into the alginate solution; c. transferring the alginate solution with the gas into a mold to form a solidified body having a desired shape; d. removing the water from the solidified body; and e. subjecting the solidified body to a conversion solution to convert only part, and not all, of the solidified body to a less soluble alginate, such that the solidified body has a surface region of the less soluble alginate and an interior region remains composed of a more soluble alginate.

35. The method of claim 34, wherein the step of removing the water comprises freeze drying.

36. The method of claim 34, wherein the more soluble alginate is sodium alginate and the less soluble alginate is calcium alginate.

37. The method of claim 36, further comprising incorporating a starch in finely divided particulate form into the alginate solution so that when the calcium alginate is formed, it precipitates about the starch particles to minimize shrinkage of the solidified body during the conversion of sodium alginate to calcium alginate.

38. The method of claim 37, wherein the starch degrades quickly within the body cavity in the presence of body fluid, and wherein the calcium alginate at the surface region degrades to open up the incorporated starch particles to degradation which provides an evolving porosity.

39. The method of claim 34, wherein the act of subjecting comprises dipping the solidified body into the conversion solution.

40. The method of claim 34, comprising sizing and shaping the porous implant so as to fit within the cavity and to conform the tissue lining of the cavity about the porous implant.

41. The method of claim 34, wherein the alginate solution includes a radiopaque imaging agent.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIG. 1 is a flow chart that schematically illustrates a method for forming an implant embodying features of the present invention.

[0016] FIG. 2 is a schematic elevational view in section of a system for mixing components to make an implant embodying features of the invention.

[0017] FIG. 3 is a schematic elevational view in section illustrating pouring the mixture into a mold to form the implant.

[0018] FIG. 4 is a schematic elevation view in section illustrating placing the dried porous body into a solution of CaCl.sub.2) to convert the soluble alginate to a less soluble alginate.

[0019] FIG. 5 is a transverse cross-sectional view of an implant after treating in the solution of CaCl.sub.2).

[0020] FIG. 6 is a transverse of an implant embodying features of the invention having an orientation marker with three radiopaque elements.

[0021] FIG. 7 is a scanning electron micrograph (30X) of a sectional view of an implant embodying features of the invention taken near the surface of the implant.

[0022] FIG. 8 is a scanning electron micrograph (30X) of a sectional view of an implant embodying features of the invention taken in the interior of the implant.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0023] FIG. 1 is a flow chart that schematically illustrates a method for forming an implant which embodies features of the invention. Specifically, in the first step 10 a bioabsorbable material (chitosan or a soluble alginate) is mixed with water along with a powdered or particulate radiopaque imaging agent such as barium sulfate. A pore forming agent such as a gas may also be incorporated into the mixture. In second step 11, the mixture, which has to a certain extent gelled, is poured into a mold. The mold has a forming surface which puts the mixture into a desired shape where it solidifies or hardens to the point where it is self-supporting in the formed shape. In the illustrated case, the shape is spherical. In the third step 12, the formed body is removed from the mold and in step 13 water is removed from the body, preferably by freeze drying or air drying, to form a porous body. In the fourth step 14a, if the porous body is formed of chitosan, the residual acid in the body is neutralized with a suitable base such as ammonium hydroxide, rinsed and dried. In the fourth step 14b, if the porous body is formed of alginate, the porous body is dipped into a solution of CaCl.sub.2), where at least part of the sodium alginate is converted to the less soluble calcium alginate, rinsed and dried. An orientation marker(s) may be inserted into the porous body by cannula or one or more passageways may be provided in the porous body so that the orientation marker(s) may be pushed to the desired location within body.

[0024] FIG. 2 illustrates adding the bioabsorbable chitosan or sodium alginate and barium sulfate powder to a body of water 20 contained in a suitable container 21. The water 20 is mixed with the mixing element or propeller 22 attached to rotating shaft 23. Bubbles can be whipped into the mass or other pore forming agents can be introduced into the body of water 20. Additionally, water soluble materials can be added so that they may subsequently be dissolved away after the body has been dried. As shown in FIG. 3, the body of fluid or gel is then poured into a spherical mold 24 which has an upper half 25 and a lower half 26 that are interconnected by brackets 27 and 28. After the body has set, water is removed, e.g. by freeze drying, so as to form a porous spherical body 29. If the body contains chitosan, the body is treated with a base to neutralize the residual acid. If the body contains sodium alginate, then as shown in FIG. 4, the porous spherical body 29 is introduced into an aqueous CaCl.sub.2) solution 30 in container 31 where at least part of the sodium alginate is converted to calcium alginate that quickly precipitates. A transverse section of the final implant 32 is schematically illustrated in FIG. 5.

[0025] FIG. 6 is a transverse cross-section of an implant 33 which has three imageable radiopaque elements 34 (e.g. gold particles) situated within the interior of the implant and spaced inwardly from the outer surface. The three radiopaque elements (e.g. imageable gold particles) are shown at the apices of an equilateral triangle which can be used as a guide for the relative positioning between the patient's breast and a linear accelerator to provide effective irradiation of tissue surrounding the lumpectomy cavity in the patient's breast. Minimally, there should be two radiopaque elements to define a line and preferably three to define a plane. However, there may be more but they should be on the same plane. The radiopaque imaging agent (barium sulfate) in the implant enables the exterior margins of the implant to be imaged in a CT scan and this facilitates determining an appropriate irradiation dosage plan for the linear accelerator to ensure effective treatment of any residual cancer cells remaining in the cavity lining after the lumpectomy.

Example I

[0026] An acidic aqueous solution (12.5% acetic acid) was prepared containing 4% by weight chitosan and 2% by weight barium sulfate. The solution was placed in a spherical mold and was then frozen in the mold at 30 C. for 16 hours. The frozen body was removed from the mold and lyophilized for 3 days to remove water. The lyophilized body was neutralized in a 10% solution of ammonium hydroxide for one hour and then rinsed free of the ammonium hydroxide with deionized water. The body was vacuum dried for 16 hours. The body had the spongy consistency approximating breast tissue and had sufficient compressive strength to support breast tissue surrounding a lumpectomy cavity. It comprised 67% chitosan and 33% barium sulfate. A SEM micrograph (30X) of the surface porosity is shown in FIG. 7 and a SEM micrograph (30X) of the central porosity is shown in FIG. 8. The implant had the spongy consistency approximating breast tissue. The implant could be made harder by increasing the amount of chitosan.

Example II

[0027] A quantity of sodium alginate (0.5 to about 4% (wt.)) is dissolved in water to form a paste, viscous fluid or gel and air or other biocompatible gas is introduced into the mixture. The mixture is placed in a mold of a desired implant shape and then freeze dried or air dried in the desired shape. The formed implant structure of sodium alginate is introduced into a solution of calcium chloride (0.5 to about 4% (wt.)) where at least part of the sodium alginate is converted to calcium alginate which precipitates. The precipitated porous structure of the implant is introduced into a body cavity from which tissue has been removed. The implant remains at the site for sufficient period of time so as to act as scaffolding to facilitate tissue in-growth within the body cavity. Starch, such as corn starch in finely divided particulate form, can be incorporated into the sodium alginate-water mixture so that when the calcium alginate is formed, it precipitates about the starch particles to minimize shrinkage during the conversion of sodium alginate to calcium alginate. The starch degrades quickly within the body cavity in the presence of body fluid. The alginate on the surface of the implant degrades to open up the incorporated starch particles to degradation which provides an evolving porosity. The weight ratio of starch to alginate can range from about 15:1 to about 1:1.

Example III

[0028] This example is similar to Example II except 30 grams of salt (NaCl) granules are mixed with about 30 ml of 3% (wt.) sodium alginate aqueous solution. The solution placed in a spherical mold and then is frozen for 4 hours. The frozen implant was removed from the mold and placed in a 2% (wt.) calcium chloride solution, forming calcium alginate gel and dissolving at least some of the incorporated salt granules to form a porous structure. The implant had the spongy consistency approximating breast tissue. The implant could be made harder by increasing the amount of sodium alginate in solution, decreasing the amount of salt or decreasing the size of the salt granules.

[0029] While one or more particular forms of the invention have been illustrated and described herein in the context of an implant, particularly a breast implant for use after a lumpectomy, it will be apparent that the implant having features of the invention may find use in a variety of locations and in a variety of applications where tissue has been removed. Moreover, various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited to the specific embodiments illustrated. It is therefore intended that this invention to be defined by the scope of the appended claims as broadly as the prior art will permit, and in view of the specification, if need be. Moreover, those skilled in the art will recognize that features shown in one embodiment may be utilized in other embodiments.

[0030] Terms such as element, member, device, section, portion, step, means and words of similar import when used in the following claims shall not be construed as invoking the provisions of 35 U.S.C. 112(6) unless the following claims expressly use the term means followed by a particular function without specific structure or expressly use the term step followed by a particular function without specific action. All patents and patent applications referred to above are hereby incorporated by reference in their entirety.