ITPI20070089A1 - DEVELOPMENT OF INNOVATIVE BREATHABLE PROSTHESES TESTED AND TEXTURED COVERED WITH HIGHLY BIO-COMPATIBLE MATERIALS - Google Patents

Description

Title

"Development of innovative smooth and textured breast implants coated with highly biocompatible materials"

Summary

The present invention relates to the development of a production process on a pilot scale for the production of innovative, waterproof, smooth and textured permanent breast prosthesis prototypes, coated with biocompatible materials. Breast implants currently used in breast replacement in reconstructive plastic surgery or in breast augmentation in additive plastic surgery, have casings made with silicone elastomers filled with highly cohesive silicone gel and with a textured surface using inorganic materials. The breast implants described in the present invention have innovative aspects as regards: 1. development and characterization of waterproof envelopes of the prosthesis; 2. development of texturing processes; 3. development of filling materials; 4. development and characterization of highly biocompatible coatings. Of particular importance is the coating with turbostratic pyrolytic carbon with a thickness of 0.3-0.8 microns never previously made on textured prostheses and which is responsible for most of the advantages that these implants have compared to those on the market so far.

State of the art relating to the present invention

The present invention relates to the production of innovative, waterproof, smooth and textured permanent breast prosthesis prototypes, coated with biocompatible materials. These breast implants are used in breast replacement in reconstructive plastic surgery or for breast augmentation in additive plastic surgery, they have casings made with silicone elastomers filled with highly cohesive silicone gel and with a textured surface using inorganic materials. In recent years, attempts have appeared in the literature to coat envelopes with a thin film of highly biocompatible materials. The market for breast implants is expanding rapidly due to an ever-increasing demand for reconstructions resulting from mastectomy operations and an increasingly widespread aesthetic requirement.

This phenomenon is associated with the demand for increasingly safe long-term prostheses It is known, also due to the enormous importance given by the media, of the seriousness of the phenomena encountered in the use of polymeric prostheses (polyurethanes and silicones) for surgery plasticity and aesthetics and the attention that the control authorities in the health field (especially in the United States) have paid to these materials, coming to suspend the use of some prostheses in use.

Despite the considerable progress in the choice of materials and their surface treatment, still today, in the application of long-term prostheses as in the case of breast implants, the phenomena of interaction between the surface of the device and the biological tissues with which it enters into are critical. contact.

A typical reaction mechanism of the biological tissue in contact with the prosthesis is the formation of a periprothetic capsule in fibrous tissue as a consequence of an inflammatory process (foreign body reaction), which can create a situation of discomfort and then pain up to force the removal of the prosthesis itself and the fibrotic capsule.

Surface treatments to improve the interface between prosthesis and biological tissue, coatings with biocompatible materials that prevent long-term contact of biological tissues with silicone, fillers made up of substances highly tolerated by the organism in case of permeation or breakage of the envelope, are the scientific and technological aspects that the present invention has addressed in order to create, by means of a process on a pilot scale and suitable for being transferred on an industrial scale, a protqtipal series of permanent, waterproof, textured and coated breast implants with highly biocompatible

Detailed description of the invention

The present invention relates in whole or in part to the following stages of the production process of breast prosthesis prototypes.

1. Development and characterization of waterproof shells for the prosthesis

Realization of waterproof silicone gel casings alternative to those currently used.

2. Development of texturing processes

Realization of texturing with techniques other than those described in the literature.

3. Development of filling materials

Realization of filling materials with cohesive characteristics

4. Development and characterization of highly biocompatible coatings

Creation of coatings that improve the surface compatibility of the prosthesis and consequent reduction of the thickness and consistency of the periprotetic capsule

1. Development and characterization of waterproof shells for the prosthesis

In breast implants currently on the market, consisting of a bilicone envelope and filled with silicone gel, the drawback of silicone gel exuding from the implants often occurs with consequent side effects (inflammation, mutagenicity). In this invention, polymers of an elastomeric nature have been identified, with different chemical and physical characteristics, most suitable for making a multilayer casing with a high guarantee of impermeability.

Initially, various silicone materials were selected, subsequently new polymeric materials belonging to the class of thermoplastic elastomers, possibly containing fluorine, never tested in this sector were examined. Thermoplastic elastomers constitute a class of polymeric materials characterized by an elastic mechanical behavior similar to that of chemically cured elastomers.

They consist of the alternation of several blocks (at least two) of plastomeric nature A with blocks of elastomeric nature B (at least one). The simplest example is rubber Ì BS where S is styrene and B is butadiene.

The vulcanization process present in these elastomers is of a physical nature and therefore there are no low molecular weight substances, capable of interacting with the fabrics, giving rise to problems of toxicity or even carcinogenicity.

Thermoplastic elastomers can be used for the production of breast implants with high safety guarantees.

2. Development of texturing processes

The superficial penetration of fibrohistocytes and fibroblasts that induce the optimal growth of collagen fibers for the development of a thin and soft capsule around the prosthesis can be achieved by creating an interface between the prosthesis itself and the body.

This interface can be obtained through the surface texturing process of the silicone material prosthesis, which consists in the formation of small pores for a depth of about 0.1 mm distributed uniformly on the surface. There are different methods of carrying out the texturing process, but to date none of them allows to realize an ideal and perfectly reproducible texturing process.

In this invention, new texturing methods have been studied that are able to overcome the critical aspects of the processes on the market today.

The texturing process should solve the problem of the periprotic capsule but could create a greater difficulty in positioning due to the higher friction coefficient, and a larger contact surface between the silicone material and the organism. In order to find an optimal solution to these problems, as described below, the textured prostheses were coated with highly biocompatible materials.

Two completely innovative processes are described in the present invention for carrying out texturing in vivo. The first process involves the use of biodegradable and bioabsorbable polymers, miscible with the base polymer with which the casing was made; the second process is that of water-soluble polymers and also miscible with the base polymers of the casing.

Among the biodegradable and bioabsorbable polymers, the three-block copolymers of polyethylene glycol with lactic and / or glycolic acid or with e-caprolactone were examined.

The last dipping will be carried out with the mixture of these copolymers and the silicone, then proceed as usual. In vivo this type of wrapping will slowly lose the biodegradable polymer from the last layer. This will create voids very similar to texturization. Polymers with proven biocompatibility such as poly N vinyl pyrrolidone were considered as water-soluble polymers.

The texturing process will take place due to the dissolution of these polymers in water, which can be done both in vitro before implantation and in (alive if the polymer is perfectly biocompatible.

3 Development of innovative materials for the filling of casings

In the present invention, the new highly biocompatible filling materials suitable for guaranteeing the necessary characteristics of flexibility, consistency and adaptability to the prosthesis have been identified.

Currently about 50% of the prostheses on the market are filled with saline solution and the remaining 50% with silicone gel. For a small percentage, polysaccharides or other experimental materials are used.

As innovative fillings, hydrogels of synthetic, natural origin and obtained with bioartificial polymeric materials are proposed

From a physical and mechanical point of view, hydrogels are very similar to biological tissues due to their aqueous phase, high permeability to small molecules and their good mechanical properties. They are generally produced by chemical or physical crosslinking appearing from polymers of synthetic or biological origin.

A particularly interesting and new class of starting materials that has been considered is that of 'bioartificial' polymers, consisting of mixtures between synthetic polymers and natural polymers and with overall characteristics resulting from the combination of the good mechanical and processability properties of synthetic polymers with those of biocompatibility shown, in general, by biological polymers. The hydrogels proposed as potential filling agents must show perfect biocompatibility and when possible ina good biodegradability in order to eliminate any problem of biological damage caused by their leakage due to rupture of the prosthesis.

4 Development and characterization of highly biocompatible coatings

In order to improve the prosthesis-biological tissue interaction, the prostheses were coated with thin layers of biocompatible materials.

The optimal parameters have been defined for the following coatings:

pyrolytic carbon coatings deposited via sputtering

deposition of biological materials after chemical modification of the surface of the envelope by plasma

- coatings with polymers capable of controlled drug release

Pyrolytic carbon is used for the realization of implantable devices in critical positions and functions since it has a very high chemical inalterability, a high tensile strength combined with a low density, a good compatibility with cellular elements and causes a negligible alteration of the proteins.

It can be deposited on polymers as a thin film by 'sputtering', i.e. carrying out, under vacuum, a mass transfer from a pyrolytic carbon target to the substrate, obtaining high adhesion between film and substrate, the absence of chemical, thermal alterations. and mechanical properties of the substrate and the maintenance of the biological properties of the pyrolytic carbon. Furthermore, the friction coefficient of the pyrolytic carbon is extremely low compared to that of silicone and therefore a coated prosthesis would minimize the trauma to which the tissues are subjected during insertion and positioning in the site of a breast prosthesis. The other technology to be used is that of the silicone treatment via p asthma to functionalize the surface. The processes via plasma take place in and not in the liquid phase, they are rapid and can be carried out continuously and furthermore the material and treated leaves the process in an already sterile form. The surface characteristics that can be modified (wettability, reactivity, crosslinking, roughness) were examined in order to deposit a thin layer of biological materials (hyaluronic acid, alginates, etc.).

As regards coatings with polymers capable of releasing drugs, polymers with recognized biocompatibility, biodegradable and bioabsorbable polymers with elastomeric properties close to those of the material with which the envelope are made, such as for example some new polyurethanes produced by Tecnologie Biomediche srl and loaded with drugs suitable to slow down the formation process of the periprhetic capsule (such as, for example, antineoplastic antibiotics). Once the optimal parameters were identified for deposition via 'sputtering' and for treatment via 'plasma', chemical-physical, mechanical, adhesion, permeability and biocompatibility tests in vitro were created and carried out.

Examples of realization of the devices and materials object of the invention

1 Waterproof shells of the prosthesis

1.1 Description of the best implementation of the invention

We describe the method and the most used materials for making the casings. We will refer to them for the use of innovative materials.

After an initial evaluation of the silicone materials available on the market, an elastomeric silicone with high mechanical characteristics produced by Nusil Silicone Technology and its mixtures with different thermoplastic astomers was identified as suitable for the production of casings.

The tests carried out and the tests carried out led to the identification of the parameters that allow the creation of a solution with viscosity and concentrations ideal for the realization of dipping on prosthesis models: 7.8% solute on solvent (cyclohexane) by volume, 12 h maceration , 2 h of homogenization at 300 rpm, filtration at 150 mesh.

Some models of these shapes have been made using both steel and Teflon bulk or delrin. A station was assembled and used for handling the molds on two axes through a PLC controller with speed control and the ability to program rotation times and end-of-cycle warnings.

The number of baths of the form in the solution necessary to reach a thickness of the casing that is between 0.55 and 0.75 mm, a thickness adequate to guarantee characteristics of elasticity and resistance of the casing, as verified in the subsequent tests, have been identified. of mechanical characterization. Depending on the volume of the mold used, from 20 to 24 intinctions must be made to obtain the desired thickness. It must then follow a thermal treatment essential for the mechanical-elastic characteristics. The developed process foresees a cure at 150 ° C for 20 min in a ventilated stove (with an acceptability range of 145 ° C - 155 ° C) and hot insertion and extraction from the cold stove; This is followed by the removal of the casings from the steel or Teflon forms (using a 50% water-ispropyl alcohol solution) and a post-cure period at 140 ° C for 3 hours in a Veptilàta stove with insertion and cold extraction.

We proceeded to characterize the envelopes obtained as described above through chemical-physical analysis (elemental chemical analysis, surface analysis with SEM scanning electron microscope, analysis by DSC calorimetry, infrared (IR) and ultraviolet (UV) diffractometry, examination surface by atomic force microscope, mechanical analysis by DMTA on Instrom equipment), finding the following average values: Tensile Strength (Mpa): 8.9; Tear Strength (kN / m): 36; Elongation (%): 1200; Durometer Hardness: 35; Modulus 200% (Mpa): 1.0.

To ensure the impermeability of these shells to silicone gels and other gels developed in the present invention, it was chosen to proceed with the development of a multilayer shell in order to combine the characteristics of the chosen elastomeric silicone (stability, resistance, elasticity, chemical inertness and biological) with those of another silicone that has chemical characteristics that guarantee the barrier effect for silicone molecules used for the filler of the prostheses. The material used was a silicone from Nusil Silicone Technology, the formulation of which has diphenyl groups that allow you to achieve 1 goal and to bind optimally to the elastomeric silicone thanks to mechanical characteristics very similar to the latter. The problems due to the different type of solvent with which the diphenyl silicone is supplied have been solved and a 150 micron layer of this silicone has been interposed between two elastomeric silicone layers with a thickness of 250 microns each for a total thickness of 0, 65 mm. The chemical, morphological and mechanical characterizations confirmed the above results and no changes were necessary to the manufacturing procedures of the casings as described. The permeability i. sample solutions of typical viscosity of silicone gels was found to be zero.

We describe some examples of casings made with innovative materials compared to silicone ones and described for the first time in this invention.

Examples:

Ex.l Wraps for breast implants have been made using ABA type fluorinated thermoplastic elastomers, where A is the plastomeric segment and consists of vinylidene fluoride (VF2) and B is the elastomeric block and is made up of a terpolymer: vinylidene fluoride / for fluorine methyl vinyl ether / tetrafluor | ethylene (VF2 / PMVE / TFE).

The dipping process is very similar to that described for silicone materials, but greatly simplified by the fact that the crosslinking process is not necessary, as a heat treatment is sufficient for the elimination of the solvent.

The mechanical properties are excellent.

100% modulus: 8-10 (MPa); Tensile strength: 10-12 (MPa); Elongation at break (%): 200-600; Hydraulic permeability: zero; Permeability to gels: zero.

Ex.2 In a very similar way to ex. above, all thermoplastic elastomers that are perfectly biocompatible and have suitable chemical, physical and mechanical properties can be used.

2 Texturing processes

2.1 Description of the best implementation of the invention

Two completely innovative processes are described in the present invention for carrying out in vivo texturing. The first process involves Γ the use of biodegradable and bioabsorbable polymers, miscible with the base polymer with which it was made Γ casing; the second process is that of water-soluble polymers and also miscible with the base polymers of the shell.

Among the biodegradable and bioabsorbable polymers, the three-block copolymers of polyethylene glycol with lactic and / or glycolic acid or with e-caprolactone were examined.The last dipping is carried out with the mixture of these copolymers and silicone, then proceed as follows usually. In vivo, this type of casing slowly loses the biodegradable polymer from the last layer. This will create voids very similar to texturization. Polymers with proven biocompatibility such as poly N vinyl pyrrolidone were considered as water-soluble polymers.

The texturing process occurs due to the dissolution of these folymers in water, which is done both in vitro before implantation and in vivo if the polymer is perfectly biocompatible.

3 Materials for filling

3.1 Description of the best implementation of the invention

In the present invention the following hydrogels based on natural polymers, synthetic polymers and bioartificial polymers are proposed as innovative alternatives to the silicone hydrogels described above.

3.1.1 Natural hydrogels

Gellan hydrogels

Gellan belongs to the family of polysaccharides classified as "gums" by virtue of the property of forming viscous solutions, dispersions or gels in cold or hot water.

Hydrogels have found wide industrial use for their suspension and stabilization properties and are therefore used as gelling agents, emulsifiers, adhesives, flocculants, binders, and lubricants.

By lowering the temperature of aqueous solutions of gellan, the formation of a hydrogel occurs rather abruptly.

The gelation temperature Tgel depends on the concentration of the abquose solutions of gellan; around 30 ° C for concentrations of 0.5% by weight and around 45 ° C for solutions of 2%. The transformation is thermoreversible and many authors agree in attributing it to a conformational transition of the polymer.

The gelation process is influenced by the molecular weight, the concentration of the polymer, the degree of deacetylation (if acetylated, gelation does not occur), the nature and the concentration of the added salts (the presence of the salts improves the mechanical properties of the gel).

The gellan hydrogels were prepared as described below.

The gellan used was purchased from Sigma Aldrich, the quantity of salts was measured by Perkin Elmer's Emission Spectometer Plasma 400 obtaining the following results: Na <+> 16 mg / gr, K <'> 10 mg / gr, Ca < 4> ^ 4 mg / gr Mg <++> 1 mg / gr

The pH of a 1% solution was equal to 7.76 and the freezing temperature was 35-40 ° C. The 1% gellan solution was prepared by dissolving 1 g of polysaccharide in 100 ml of distilled water at 90 ° C under continuous stirring. After complete dissolution 10 ml of solution were placed in a Petri dish and allowed to cool down to room temperature, after cooling the formation of a transparent and helistic gel was observed. As has already been said, the gelling process is influenced by the molecular weight, the concentration of the polymer, the degree of deacetylation, the nature and concentration of the added salts. By suitably varying these parameters it is possible to obtain hydrogels with characteristics similar to those described for silicone gels.

Preparation of gellan hydrogels in the form of microspheres

Gellan microspheres with a diameter between 10-25 microns were obtained using the single water / oil emulsion technique.

The aqueous phase is constituted by a 1.5% gellan solution, the oily phase by a 2% phosphatidylcholine (PC) solution (surfactant agent) in dichloromethane.

The solution of PC in dichloromethane was placed in a flask and brought to a temperature of 50 ° C, the hot solution of gellan (50 ° C) was slowly poured into the flask under continuous stirring (800 rpm) and kept stirring for 30 minutes.

Subsequently the flask was removed from the bath at 50 ° C after 2 hours at the same stirring speed, the flask was cooled in an ice bath and the speed was reduced to 200 rpm to allow the gelation of the gellan microparticles.

After cooling, the contents of the flask were placed in the fridge overnight.

The day after, the contents of the flask were placed in a separating funnel which allowed the particles to be recovered, after multiple washes with CaCl2, and the breast micro spheres were dried and characterized.

The most interesting property of gellan microspheres, which emerged during the character; nation, consists in the ability to absorb water as a function of the pH of the medium. The advantages yesterday from the use of microspheres in the production of breast implants are numerous, including easy injectability, better hydration which involves the use of smaller quantities of polymer for the same filled volume

3.1.2 Synthetic hydrogels

PVA hydrogels

Among the various techniques used to produce PVA hydrogels, the process described by Nambu [M. Nambu, European Pat. 0058497 B1 (1985)] is one of the most interesting. This method is based on a physical crosslinking obtained by repeated freezing-thawing cycles of aqueous solutions of PVA. These cycles lead to the forre action of crystallites which act as cross-linking centers between the PVA chains and produce a hydrogel with a high swelling capacity.

The spatial structure of PVA hydrogels is stabilized by intra- and intermolecular hydrogen bonds that are formed thanks to the numerous hydroxyl groups located on the polymer chain. Several studies have established that the properties of PVA hydrogels depend on:

- molecular weight and degree of hydrolysis of the polymer; - concentration of the initial PVA solution; - nature of the solvent; -temperature and duration of freezing; - defrost speed; - number of cycles.

By suitably varying the parameters described above, hydrogels with optimal characteristics for use in the production of breast implants are also obtained in this case.

3.1.3 Bioartificial hydrogels

PNIPAAm / Alginate / Gelatin hydrogels.

Alginate is a salt derived from alginic acid, a water-soluble polysaccharide of natural origin, mainly extracted from brown algae.

The presence of divalent cations, such as alkaline earth metals, allows the establishment of ionic bridges between the different chains, thus creating a gelled three-dimensional structure. from the aqueous solution.

Preparation of PNIPAAm / Alginate / Gelatin hydrogels

A solution of PNIPAAm (1% weight / volume), an alginate solution (2%) and a gelatin solution (2%) are prepared respectively.

The three solutions are mixed at room temperature in order to avoid gelation of the synthetic polymer, obtaining a homogeneous solution having a weight ratio PNIPAAm / Alginate / Gelatin 1: 2: 2.

The solution is then poured into suitable containers in which a few ml of a 2.5% CaCl2 solution are added after 5 minutes the partially gelled material is extracted from the containers and placed in a CaCl2 solution for 20 minutes in order to complete the gelation process of the 'alginate.

The samples are then placed in a 0.5 M acetic acid solution for 16 hours in order to establish ionic interactions between the gelatin and the alginate stabilizing the protein molecule. The samples are then repeatedly washed with distilled water to remove the acetic acid, the hydrogels obtained are stored in the freezer at -18 ° C.

4 Highly biocompatible coatings

4.1 Description of the best implementation of the invention

4.L1 Coatings of pyrolytic carbon deposited via sputtering

In the present invention some highly biocompatible coatings have been evaluated which allow the improvement of the interaction characteristics of the prostheses with biological tissues. As already illustrated in the previous paragraphs, the first material that was considered was pyrolytic carbon, in the particular physical state defined

which makes the atomic lattice particularly compact and above all inert against any chemical or biological interaction Several experiments of bases have shown the absence or drastic reduction of the tissue reaction in contact with devices coated in turbo straphic carbon as well as the presence of a barrier effect to diffusion substances from the substrate material within the biological tissue.

On the basis of this premise, the pyrolytic carbon coating of smooth and textured "breast implants" was carried out and the subsequent characterization highlighted the following aspects:

an extremely reduced coating is obtained (about 0.3 -0.8 microns) and therefore such as not to alter the flexibility of the silicone shell, but thanks to the compactness of the atomic lattice of the pyrolytic carbon the passage of organic molecules from the silicone towards the surrounding tissues.

- The extremely low value of the friction coefficient of the pyrolytic carbon minimizes the resistance to insertion and sliding during the positioning of the prosthesis, allowing to operate with less trauma for the insertion area

The parameters defined for the Carbofilm coating are: atmosphere 5 x 10-3 mbar; voltage 75 V; arc current 7 A; time 2 hours; source temperature 140 ° C.

4.1.2 Deposition of biological materials after chemical modification of the envelope surface by plasma.

The second class of materials that has been studied for the purpose of an innovative coating of breast implants is that of polysaccharides and in particular of hyaluronic acid, a natural polysaccharide with high hydrophilicity, biodegradable and biocompatible and whose role is decisive in many biological mechanisms. which involve and promote cell regeneration. The coating process uses a first phase consisting of the activation of the surfaces to be coated by gas in the plasma state and a subsequent one that involves the formation of a covalent chemical bond between the surface and the hyaluronic acid. We proceeded to verify whether the plasma activation process and the subsequent chemical coating reaction with hyaluronic acid were effective in improving the surface properties, without affecting the physical-mechanical characteristics of the lulk. On 2x2 cm samples and subjected to activation on both surfaces, parameters such as: gas to be used, discharge time, power for the plasma phase, concentration of reagents and reaction time for the coating phase were evaluated.

Air was used as a gas, which, with the same effectiveness as nitrogen, is cheaper and safer. A radiofrequency generator with power between 30 and 50 W was used as a discharge system. In particular, at a power of 50 W, reaction times between 15 ”and 2 min were tested. At the end of the treatment, the samples were compared with silicone casings as is, both in terms of morphology and reduction of the contact angle due to the increase in surface hydrophilicity by the hyaluronic acid layer. On samples treated for 45 sec. with plasma in air the stability of the hyaluronic acid coating was then tested over the next 24 hours by measuring the contact angle, finding a minimum variation between the first measurement at 0 hours and the last at 24 hours (from 55 ° at 59 °) verifying that the hydrophilic layer of anion molecules that remains stably adhered to the surface in the 24 hours following the treatment. For the coating reaction, the plasma-activated samples are immersed in a diluted polyethylimine bath for about 90 min. After washing the samples with water up to neutral pH, the samples are immersed in an aqueous solution of hyaluronic acid and then NHS and EDC in a concentration varying between 0.25 and 0.5% w / v are added.

After 16 hours of reaction, the samples are washed with double distilled water and dried under a laminar flow hood. The samples were then characterized using the contact angle. For the level of hydrophilicity induced by hyaluronic acid, an average of 35 ° for the contact angle with a standard deviation of 1 ° was verified on 4 samples in three different areas, confirming the homogeneity of the coating along the surface. There was also a reduction in cell adhesion using L929 fibroblasts in contact with the samples for 3 hours. The evaluation under the optical microscope showed that in the presence of the HA coating no significant adhesions are observed compared to the TQ and the decrease is estimated to be of the order of 90%. Bacterial adhesiveness was also verified through S. Epidermidis in concentrations of le <9> cfu / cm <2> for 2 hours of contact. After washing and sonification from the SEM examination there was a reduction from le <6> to 3e <3>. It therefore occurred: an increase in hydrophilic power; reduction of non-specific cell adhesion / activation

inhibition of bacterial adhesion.

4.1.3 Coatings with polymers capable of controlled drug release

For the controlled release of anti-inflammatory and antimitotic drugs, final coatings of the prostheses were used with biostable or biodegradable polymers capable of releasing these drugs contained in them, in a controlled way. Among the best polymers used for this purpose we report as an example the biodegradable elastomeric polyurethanes not produced in the present invention.

Polyurethanes represent an important subclass in the family of thermoplastic elastomers. They contain a methane bond similar to the carbam group or and consist of the alternation in a chain of soft (i.e. flexible) and hard (rigid) blocks

The development of polyurethanes degrading in a physiological environment is more recent, a main obstacle, due to the fact that the diisocyanates commonly used as precursors

for degradation of toxic or carcinogenic products, the use of either an abiatic diisocyanate derived from L-lysine (LDI) has been exceeded, whose possible degradation products in aqueous environment are ethanol and L-lysine both 1, 4-butanediisocyanate (BDI) and by putrescine degradation or a diamine involved in cell proliferation processes. The synthesis, characterization and functionalization of biodegradable polyurethanes of application interest in the biomedical sector was carried out, according to the procedures described in the literature.

The functionalization reactions of polyurethanes with peptide sequences of interest are carried out using structural units containing the peptide itself and suitable spacers as chain extenders. The structural units are synthesized according to standard solid phase peptide synthesis protocols. The role of the spacer is to ensure the conformational freedom of the peptide necessary for effective interaction with cell receptors in a biological environment. The synthesis procedure is reported in a degree thesis.

Since the invention has been described in this way, it is clear that it can be defeated in many ways. These variations cannot be considered as departures from the spirit and purpose of the invention, and if they are obvious to an expert in the field they must be considered included within the scope of the following claims.

We claim:

1 - A breast prosthesis envelope made of polymeric material is made of any thermoplastic elastomer impermeable to the gels normally used as fillers and of suitable chemical, physical and mechanical properties.

2 - A shell as in claim 1 wherein the polymeric material is any mixture of the thermoplastic elastomers.

3- An envelope as in claims 1-2 textured in vivo with the method based on the use of a last layer consisting of a mixture of the polymeric material with which the envelope is made with a biodegradable and bioabsorbable polymer, capable of releasing drugs.

4 - An envelope as in claims 1-2 textured in vivo with the method based on the use of a last layer consisting of a mixture of the polymeric material with which the envelope is made with a water-soluble polymer, capable of releasing drugs.

Claims (1)

5 - Materials for the filling of envelopes for breast implants consisting of cross-linked natural polymers, such as eg. gellan. 6 - Materials for the filling of envelopes for breast implants consisting of hydrophilic synthetic polymers cross-linked by physical or chemical means, such as eg. PVA. 7 - Materials for the filling of envelopes for breast implants consisting of bioartificial polymeric materials. 8 - A shell for breast implants as in claims 1 to 2, coated with carbofilm. 9 - A breast prosthesis envelope as in claims 1 to 2, coated after plasma treatment with highly biocompatible biological polymers such as hyaluronic acid. 10 - An envelope for breast implants as in claims 1 to 4, coated with biodegradable synthetic polymers of high biocompatibility where the coating with drugs and is capable of their controlled release.