WO2004071336A2

WO2004071336A2 - Hydrophilic fibrous capsule resistant prosthetic device

Info

Publication number: WO2004071336A2
Application number: PCT/US2004/003117
Authority: WO
Inventors: Francis Xavier Vacanti
Original assignee: The General Hospital Corporation D/B/A Massachusetts General Hospital
Priority date: 2003-02-06
Filing date: 2004-02-04
Publication date: 2004-08-26
Also published as: WO2004071336A3

Abstract

A prosthesis, such as a breast prosthesis (2), which includes a tissue contacting coating (3) of hydrophilic polymer is provided. The hydrophilic polymer includes polymers having a water content from about 35% to about 80% by weight when hydrated. The hydrophilic polymer may be used with prosthesis for cartilage, bone, muscle, fat, artery, vein, heart valve, tendons, tendon sheaths, dura, skin, trachea, bronchi, esophagus, teeth, and hair. One useful hydrophilic polymer is poly hydroxyl ethyl methacrylate.

Description

HYDROPHILIC FIBROUS CAPSULE RESISTANT PROSTHETIC DEVICE

I

BACKGROUND OF THE INVENTION

The present invention relates to prostheses for use in reconstructive surgery, and more particularly to prostheses useful for breast reconstruction surgery that are able to retain their shape and compliance. The invention also relates to methods for making such prostheses.

Breast cancer affects one out of eight women, and is often treated by techniques including mastectomy. The choice to undergo a mastectomy is sometimes determined to by the patient's expectation of a satisfactory breast reconstruction. Thus the need for an effective breast reconstruction technique is paramount.

Current breast reconstruction techniques involve the use of a breast prosthesis, or transfer of tissue (e.g., part of the abdominal wall) to the region of the affected breast(s) by a variety of "flap" techniques.

Breast prostheses are usually in the form of saline or gel-filled polymeric (e.g., poly-dimethyl siloxane) vessels that are implanted at the breast site. Although the recovery period for reconstructive surgery utilizing prostheses is shorter than other reconstruction techniques, drawbacks do exist. For example, scar tissue, or a fibrous capsule can tighten around the prosthesis, causing it to lose shape and compliance. Over time, such prostheses may distort and harden.

Flap-type reconstruction techniques require a prolonged recovery period because tissue is removed from one part of the patient's body and implanted in the breast region. One common flap technique is the Transverse Rectus Abdominis Myocutaneous (TRAM) flap in which tissue is transferred from the abdomen to the breast. This technique requires the careful repair of the donor site, and can still lead to weakness in the abdominal wall. It would thus be desirable to provide improved materials and techniques for the use in reconstructive surgery of the breast and other parts of the body.

SUMMARY OF THE INVENTION

The present invention provides a prosthesis device containing a hydrophilic polymer, wherein the hydrophilic polymer reduces the formation of encapsulating fibrous tissue. When hydrated, the hydrophilic polymer may have a water content of more than about

30% by weight. One hydrophilic polymer useful for the present invention is poly hydroxy ethyl methacrylate (PHEMA).

In one embodiment, the hydrophilic polymer is used with a breast prosthesis. The hydrophilic polymer covers the surface of the breast prosthesis and protects the prosthesis from the formation of encapsulating fibrous tissue. The hydrophilic polymer may also be used with prostheses for tissue such as cartilage, bone, muscle, fat, artery, vein, heart valve, tendons, tendon sheaths, dura, skin, trachea, bronchi, and esophagus. In particular, the hydrophilic polymer can substitute for tissue adjacent to damaged or repaired tissue to reduce or prevent adhesion between the damaged tissue and adjacent tissue.

In another aspect of the invention, a prosthesis, such as a breast prosthesis, is formed of a hydrophilic polymer.

In yet another aspect, the present invention provides methods for reconstructing a breast using a breast prosthesis including the steps of covering a breast prosthesis in a layer of a hydrophilic polymer, such as poly hydroxy ethyl methacrylate, hydrating the covered breast prosthesis, and surgically implanting the breast prosthesis. BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings:

FIG. 1 illustrates a prosthetic beast implant of the present invention;

FIG. 2 is a photograph illustrating the effectiveness of a prosthesis constructed according to the present invention;

FIG. 3 is a photograph illustrating a side-by-side comparison of tissue growth adjacent to a prior art poly-dimethyl siloxane implant and tissue growth adjacent to a poly 2-hydroxy ethyl methacrylate implant according to the present invention;

FIG. 4 is a photomicrograph illustrating tissue formation adjacent to a poly- dimethyl siloxane implant; and

FIG. 5 is a photomicrograph illustrating tissue formation adjacent to a poly 2- hydroxy ethyl methacrylate implant according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a hydrophilic polymer that reduces or eliminates the formation of unwanted fibrous tissue. The hydrophilic polymer greatly improves the performance of prosthetic devices. In one embodiment, the present invention includes a prosthetic device in which the outer shell of the prosthesis is enveloped by the polymer. The hydrophilic polymer coating resists fibrous capsule formation and thereby improves the performance of prosthetic devices, such as breast prostheses, which can be distorted and hardened by encapsulation. The prosthesis of the invention functions as a breast prosthesis for use during reconstructive surgery following a mastectomy, or to augment or reshape a healthy breast. The present invention may also be adapted to form prostheses for use with other tissue or organs, including, but not limited to cartilage, bone, muscle, fat, artery, vein, heart valve, tendons, tendon sheaths, dura, skin, trachea, bronchi, esophagus, teeth, and hair.

The hydrophilic polymer may be any non-toxic biocompatible polymer with sufficient water content when hydrated. In one embodiment the hydrophilic polymer is poly hydroxy ethyl methacrylate (PHEMA) with a water content of at least about 38% by weight, as further discussed below. A person of skill in the art will appreciate that a variety of hydrophilic methacrylic acid based polymers may also be used.

In addition, the hydrophilic polymer of the present invention preferably provides a soft, flexible feel. This flexibility is preferably reflected in the hydrophilic polymer having a low elastic modulus.

The hydrophilic polymer may be in the form of a hydrogel derived from the polymerization of monomers such as hydroxy ethyl methacrylate (HEMA), 2-hydroxy ethyl methacrylate, glyceryl monomethacrylate (GMA)₉ n-vinyl-2-pyrrolidone (NVP), acrylic acid, methacrylic acid (MAA), and combinations and variations thereof. In other embodiments the hydrogel is a copolymer of HEMA and GMA (having a water content of about 48 % by weight), a copolymer of HEMA and MAA (with about 55% water by weight), or a copolymer of MMA and NVP (with about 70% water by weight). In a further embodiment the hydrophilic polymer is a copolymer of HEMA and co-monomer selected to improve stability, texture, or other mechanical or chemical characteristics. Exemplary co-monomers include, but are not limited to, polyethylene oxides; polypropylene oxides; polyvinyl alcohols; polyvinyl pyrrolidones; polyglycols; polyethylene imines; polyacrylamides; polyacrylonitriles; polyHEMA polymers;

HYP AN polymers; HEPU polymers; starch glycolate polymers; crosslinked, acrylic acid-based polymers; hydrophilic polyurethanes; carbohydrates; and proteins. It will also be understood that derivatives of such polymers, copolymers, and/or blends or mixtures of the various polymer families may be used in this invention.

In a preferred embodiment, the hydrophilic polymer is a hydrogel formed from cross-linked PHEMA. In a particularly preferred embodiment, the hydrogel is PHEMA.

The water content of the hydrophilic polymer may be varied according to the polymer chosen and its intended placement. The equilibrium water content of the hydrophilic polymer may be adjusted by the balance between hydrophilic/hydrophobic groups, the amount of cross-linking, the length between links, and the size and distribution of the polymer mesh. Equilibrium water content may be increased by co- polymerization with a more hydrophilic monomer. In any event, the water content should be sufficient to reduce the formation of fibrous tissue. In one embodiment the hydrophilic polymer has a water content above about 20%, and preferably above about

35% by weight. In a more preferred embodiment the water content is about 38% by weight. In a most preferred embodiment the water content ranges from about 35% to about 80% by weight. One skilled in the art will appreciate that water content will vary depending upon the intended use of the hydrogel or hydrogel-coated prosthesis.

One skilled in the art will appreciate that water content may be adjusted according to the use of the implant. Where the hydrophilic polymer is used as a coating, and does not provide structural support, the water content may range from about 0% to about 80%. Those hydrophilic polymers having a higher water content may also provide reduced fibrous encapsulation and a softer, more flexible feel. Where the implant is used as a prosthesis such as a breast implant the water content of the hydrophilic polymer may range from about 35% to about 80% and more preferably from about 40% to about 75%o. Where the hydrophilic polymer is used in an application in which it must provide structural support or strength to the prosthesis, a lower water content may be used, for example from about 20% to about 60%. It is believed that the presence of the hydrophilic polymer on the tissue- contacting surface of a prosthesis tends to reduce the formation of fibrous encapsulation because the high water content enables it to more closely mimic real tissue. Therefore, the hydrophilic polymer may form a structural component of the prosthesis surface or it may be applied to a completed prosthesis included as a coating on the surface of a prosthesis. In one embodiment, only the outer tissue-contacting surface of the prosthesis is covered with hydrophilic polymer. Alternatively the entire prosthesis, including the outer-tissue contacting surface, may be constructed primarily of hydrophilic polymer.

Where the hydrophilic polymer is formed in a layer over the outside of a prosthetic device, it may be formed on the prosthesis in a variety of ways such as painting or dipping the prosthesis in a solution of partly polymerized polymer. After coating, the polymerization is then completed. Other methods may include shaping a block of polymerized hydrophilic polymer and adhering the shaped polymer to the surface of the prosthesis.

When used as a coating for a prosthesis, the hydrophilic polymer can be present in a coating of uniform thickness. Depending on the prosthesis and its use, the thickness of an effective coating may range from less 0.1 mm to the full thickness of the prosthesis. In another embodiment, the thickness of the coating varies. An embodiment that utilizes a varying thickness may help to create a prosthesis with a more natural form. In the case of a breast prosthesis, the coating may vary from a posterior surface thickness of about 4 mm to an anterior surface thickness of about 1 mm.

Additives, fillers, and bioactive compounds may be added to the hydrophilic polymer. Further, reinforcing additives, e.g. Kevlar, may be used to provide additional strength. Bioactive drugs may also be incorporated into the prosthesis to help resist fibrous tissue formation.

FIG. 1 shows a breast prosthesis constructed according to the present invention. The breast prosthetic device 1 includes a saline-filled bag 2 containing about 100 to 300 ml of fluid. The bag is shaped to provide a natural breast shape. Other prostheses would be shaped according to their desired use. The bag is enveloped by a hydrogel 3, such as poly hydroxy ethyl methacrylate, which does not distort the desired shape of the prosthesis.

The hydrophilic polymer is particularly useful with breast prostheses because it has been found to limit the growth of fibrous encapsulation around a breast prosthesis, and thus enable the prosthesis to keep its original shape and compliance. In one embodiment, a breast prosthesis is enveloped by a hydrophilic polymer having a thickness of about 1 to 4 mm. In another embodiment, the hydrophilic polymer envelope has a thickness of approximately 1 mm which provides increased flexibility and the ability to move with the underlying fluid filled bag. The prosthesis is prepared for implantation by hydrating the prosthesis by submersion in normal saline, and then implanting the prosthesis according to accepted surgical techniques to augment or replace a natural breast. Alternatively, as described below, a breast prosthesis according to the present invention may be implanted beneath the skin rather than beneath the pectoral muscle. One skilled in the art will appreciate that other materials of suitable size and compliance may be used instead of a bag filled with saline. Such material include, but are not limited to, other fluids, as well as, various elastomers and hydrogels, including PHEMA.

The following non-limiting example serves to further illustrate the present invention.

EXAMPLE

Preparation of Implants:

Silastic discs representing prior art prosthesis, were prepared by polymerization of 10 ml dimethyl siloxane with 1 ml of curing agent (SYLGARD 184 silicone elastomer kit, available from Dow Corning) according to manufacturer's instructions in a 10 ml syringe. After polymerization was completed, the poly-dimethyl siloxane was removed from the syringe and the resulting rod was sliced into discs, each having a thickness of 4 mm. After slicing, the discs were autoclaved and stored in 50 ml of sterile saline. Poly hydroxy ethyl methacrylate (PHEMA) was prepared from the monomer by free radical polymerization. The polymerization was initiated by the addition of 2 drops of methyl ethyl ketone peroxide to 10 ml of 2-hydroxy ethyl methacrylate and heated to 90 °C for 10 minutes. The resulting rod of PHEMA was removed from the tube, hydrated for 1 week in distilled water then sliced into discs of 4 mm thickness. After slicing, the discs were dehydrated by evaporation at room temperature, autoclaved and stored in 50 ml of sterile saline.

Insertion of Implants :

Five female Lewis rats weighing 150 -250 g were anesthetized by inhalation of 2% forane in oxygen. After loss of consciousness, each rat was placed in the prone position, and the back cleared of fur with electric clippers from the cervical to lumbar region. The thoracic region was then prepped with BETADINE, covered with a TEGADERM, and the rat was covered with sterile drapes. A longitudinal skin incision of approximately 2 cm was made over the middle of the thoracic spine and a pocket large enough to accommodate a disc was created by blunt dissection of the loose connective tissue between the skin and the underlying deep muscle. A PHEMA disc was placed in the right pocket and a poly-dimethyl siloxane disc was placed in the left pocket. The skin was then closed in one layer with interrupted sutures and the animals allowed to awaken. Sutures were removed at one week.

Assessment of Fibrous Encapsulation:

After 6 weeks of implantation, the rats were anesthetized by inhalation of 2% forane in oxygen. After loss of consciousness, each rat was placed in the prone position, the back cleared of fur with electric clippers from the cervical to lumbar region and the skin opened with a midline longitudinal incision from the cervical region to the lower lumbar region. The skin edges of the incision were reflected laterally, revealing the region of implantation without any dissection. The appearance of the implant and surrounding tissue of the two implants were noted and compared to each other. The presence or absence of fibrous encapsulation was determined by the gross appearance of the implant and surrounding tissue and the resistance to cutting of the tissue around the implant. The poly-dimethyl siloxane implants were compared to the PHEMA implants using the one-sided sign test.

Results:

FIG. 2 is typical of the appearance of the two discs at 6 weeks of implantation. In this photograph, the PHEMA disc (on the right) is readily observed. The PHEMA disc is not surrounded by a tissue which is resistant to cutting. Conversely, the poly- dimethyl siloxane disc on the left is embedded in fibrous tissue obscuring the view of the disc. The tissue surrounding the poly-dimethyl siloxane disc is resistant to cutting.

There was no evident fibrous tissue in all 5 implants of PHEMA whereas all five poly dimethyl siloxane discs appeared to be embedded in fibrous tissue. The difference in fibrous encapsulation is statistically significant (p = 0.0312).

It is evident that a prosthesis with a surface composed of a material that does not induce formation of a fibrous capsule would be desirable for both reconstruction patients as well as patients having implants for augmentation. Such a material would enable the implant to maintain its shape and compliance in order that the initially acceptable cosmetic result remains acceptable.

Photomicrographs of full thickness, unstained segments of formalin-fixed capsules also illustrate the effectiveness of PHEMA in reducing fibrous formation. FIG. 3 is a photograph of the segments of formalin-fixed capsules which have been peeled away from the curved surface of the implanted discs. The tissue 40 (on the left side of the photograph) was removed from a poly-dimethyl siloxane disc. This specimen is stiff, opaque, vascular and resistant to cutting. This specimen is in marked contrast to the tissue 42 removed from the PHEMA disc as shown on the right. Tissue 42 in FIG. 3 was obtained from the same rat as tissue 40. Tissue 42 is flexible, transparent, less vascular and not resistant to cutting as compared to tissue 40.

Photomicrographs of the specimens shown in FIG. 3 are presented in FIGS. 4 and 5. The tissue in FIG. 4 was obtained from the poly-dimethyl siloxane disc and is readily seen to be comprised of densely packed parallel fibers. The specimen in FIG. 5 was obtained from the PHEMA disc in the same rat as that in FIG. 4. FIG. 5 demonstrates that the PHEMA disc results in fewer fibers, and they are irregularly distributed and not oriented in any particular pattern. Also, the vessels are smaller than those from the poly-dimethyl siloxane disc with many more cells visible.

The poly-dimethyl siloxane implants in this study tend to be encapsulated by a dense fibrous connective tissue with the fibers aligned in the same direction. The tissue is stiff and vascular. PHEMA implants, by contrast, are surrounded by loose connective tissue which is flexible and comprised of more cells, fewer and non-aligned fibers and small blood vessels.

Not only does the hydrophilic polymer improve the characteristics of the prosthetic, but the reduction of fibrous encapsulation also allows the prosthetic to be implanted directly under the skin. Breast prostheses are typically placed under the pectoral muscle to hide the fibrous reaction and hopefully reduce fibrous encapsulation by the action of the muscle contraction in massaging the fibrous capsule. The procedure of preparing the muscle pocket for implantation is very painful as the muscle has to be stretched to accommodate the implant. This pain can be eliminated by subcutaneous implantation. In addition, subcutaneous implantation also provides a better cosmetic result which was previously unavailable because of the eventual fibrous contraction.

The reduction of fibrous tissue formation is also useful to limit unwanted tissue adhesion. While fibrous tissue growth can assist with healing, it can also reduce the mobility of damaged tissue by adhering injured tissue to the surrounding tissue. To assist with the proper healing of damaged or repaired tissue, a coating of the hydrophilic polymer can block or reduce this unwanted fibrous tissue adhesion. For example, the hydrophilic polymer can act as a tendon sheath. When a tendon is ruptured, the ends of the tendon can be sutured together. While the tendon will heal by scar formation, the associated fibrous tissue may also fix the tendon to adjacent tissue. This is problematic because the tendon needs to glide freely within the tendon sheath. By substituting the hydrophilic polymer for the adjacent tissue (e.g., wrapping or otherwise applying the hydrophilic polymer to the sutured tendon), the unwanted fibrous adhesions between the tendon and adjacent tissue can be reduced or eliminated. The hydrophilic polymer can similarly help in other tendon and ligament repairs (e.g., ACL repair), bowel surgery, lung surgery, or any other procedure where the reduction of tissue adhesion is desired.

A person skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publication and references cited herein are expressly incorporated herein by reference in their entity.

What is claimed is:

Claims

CLAIMS:

1. A prosthetic device containing a hydrophilic polymer with a high water content, wherein the hydrophilic polymer is present in an amount effective to reduce the formation of encapsulating fibrous tissue.

2. The device of claim 1, wherein the hydrophilic polymer is a hydrogel derived from the polymerization of monomers selected from the group consisting of hydroxy ethyl methacrylate (HEMA), 2-hydroxy ethyl methacrylate, glyceryl monomethacrylate (GMA), n-vinyl-2-pyrrolidone (NVP), acrylic acid, and methacrylic acid (MAA), and combinations thereof.

3. The device of claim 1 , wherein the hydrophilic polymer is poly hydroxy ethyl methacrylate (PHEMA).

4. The device of claim 2, wherein the hydrophilic polymer has a water content between about 35% and about 80%.

5. The device of claim 1, wherein the prosthesis is a breast prosthesis.

6. The device of claim , wherein the hydrophilic polymer is poly hydroxy ethyl methacrylate.

7. The device of claim 1, wherein the prosthesis is suitable to replace tissue selected from the group consisting of cartilage, bone, muscle, fat, artery, vein, heart valve, tendons, tendon sheaths, dura, skin, trachea, bronchi, and esophagus.

8. The device of claim 1, wherein the hydrophilic polymer is present as an outer layer containing poly hydroxy ethyl methacrylate having a thickness ranging from about 1 mm to about 4 mm.

9. The device of claim 1, wherein the device is a breast prosthesis and the outer layer comprises a hydrophilic polymer, and the thickness of the outer layer varies.

10. The device of claim 1, wherein the device is a breast prosthesis constructed from poly hydroxy ethyl methacrylate.

11. The device of claim 1, wherein the hydrophilic polymer is selected from the group consisting of poly hydroxy ethyl methacrylate, a copolymer of hydroxy ethyl methacrylate and glyceryl monomethacrylate, a copolymer of hydroxy ethyl methacrylate and methacrylic acid, and a copolymer of methyl methacrylate and N-vinyl-2-pryrrolidone.

12. The device of claim 1, wherein the prosthesis is a tendon sheath.

13. A method for reconstructing a breast using a breast prosthesis, comprising the steps of: coating a breast prosthesis in a layer of poly hydroxy ethyl methacrylate; hydrating the coated breast prosthesis; and surgically implanting the breast prosthesis.

1 . The method of claim 13, wherein the breast prosthesis is implanted between the pectoral muscle and the skin that defines the breast.

15. A method for surgically repairing tendons or ligaments, comprising the steps of: suturing a free end of connective tissue; and covering the sutured tissue with a sufficient quantity of poly hydroxy ethyl methacrylate to reduce tissue adhesion between the surgically repaired connective tissue and the surrounding tissue.