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Development of bio-active integrated ocular implant for anophthalmic human patients.

Hydroxyapatite (HAp) powder was synthesized in the laboratory through wet chemical route and mixed with naphthalene powder in 1: 3 w/w ratio, which was homogenized, pressed iso-statically and subsequently turned to prepare samples of predetermined size and shape. They were finally sintered at 1200-1300[degrees]C for 4 hrs. and were tested for different physical, mechanical and tribological properties and used for clinical trials to establish non-toxicity and bio-compatibility. The material in granular form was introduced to Mongrel dogs and thereafter to human patients for bone-grafting operations and the results are discussed. Finally, out of these materials highly porous orbital implants of different designs have been prepared and after thorough sterilization they have been introduced to the Mongrel dog and subsequently to the anophthalmic human patients after enucleation / evisceration surgery. The results of the preliminary short-term clinical investigations are outlined and performances are compared with that of the conventional ones.

INTRODUCTION

Post Enucleation Socket Syndrome (PESS) (significant loss of orbital tissue after the loss of an eye) which is exhibited through an anophthalmic appearance with a retraction or ptosis of the upper eye-lid and orbital floor fracture (when the orbital rim is occluded by an appropriately sized object by which the eye-ball is pressurized resulting fracture of the orbital floor) are very common post-operative problems after enucleation / evisceration surgery. The extraocular muscles, which surround the eye and control its movement and adjacent orbital tissues may prolapse through the fracture causing malposition of the eye and double vision. Various implants made of different materials have been clinically used so far with limited success to counter this problem and therefore, the search continues. Since 1985 porous hydroxyapatite [1] has been used as an ocular implant for reconstruction after enucleation and evisceration surgery. This bioactive material is totally nontoxic, biocompatible, and non-allergenic to humans and has a special feature to become invested with fibrovascular tissues [2] of the orbit. Therefore this implant exhibits, in turn, an excellent motility and superior cosmesis and results minimum complications in the form of infection, extrusion, and migration of the implanted eye-ball.

India is a place of staggering 20 million blind people who generally come from a very poor background. About half of this population are one eyed and suffer from a peculiar problem: they are neither declared as handicapped persons to receive special support from the government nor they are accepted by the society because of the repulsive appearance of the blind eye. The expensive imported implants made out of coral [3] are totally out of reach of these patients while the substandard local ones without eyeball movement do not serve their purpose. Therefore, it is felt essential to initiate this activity to develop this implant with international quality but with affordable price for the huge poor population of our country.

In the present study medical grade hydroxyapatite powder was synthesized by wet chemical route, which was characterized thoroughly in-vitro and in-vivo prior to implant in human patients for bone grafting [4]. Finally, a composition was formulated to develop sintered hydroxyapatite with 75% porosity, from which orbital implants of different designs (Fig.1) were developed. These implants, also, were introduced into Mongrel dog to ensure their functional performance and thereafter implanted to five human patients through Eye Care and Research Centre, Kolkata and the preliminary results of the post-operative studies have been outlined.

[FIGURE 1 OMITTED]

EXPERIMENTAL

Materials and Methods

Analytical Reagent (A. R.) grade ortho-phosphoric acid solution [5] was added drop-wise to a continuously stirred suspension of calcium hydroxide maintained at a fix temperature of 800 C to produce milky gelatinous precipitate which was aged, filtered and washed thoroughly. After drying at 70[degrees]C, the precipitate was calcined at 800[degrees]C and ground in a planetary mill. The powder prepared was characterized in-vitro through chemical analysis, XRD, IR-spectroscopy, particle size distribution and in-vivo for toxicity and biocompatibility. For in-vivo characterization, however, a solution was prepared by extracting the filtrate, which was obtained from the mixture of 25 ml of Normal Saline and 1 g of hydroxyapatite powder heat treated at a temperature of 121[degrees]C for 60 minutes. The solution was injected to five mice and equal numbers of albino rabbits with a dosage of 50 ml / Kg and 200 il / Kg of body weight for systematic toxicity and intracutaneous toxicity estimation respectively.

Bone grafting

This hydroxyapatite powder was first mixed with naphthalene powder and made in granular form with the PVA binder, dried at 60[degrees]C for 200 hrs. and sintered at about 1250[degrees] C. Granules of about 3 to 5 mm in diameter with a porosity of about 50% were implanted in the Mongrel dog as bone grafting material and bond formation in the interface was studied through the radiographic and histological observations up to 20 weeks after the operation. Subsequently these granules were implanted in three human patients who were suffering from bone tumor / fracture and post-operative studies were performed through thorough clinical, radiological and histological observations.

Development of the Prostheses and their Clinical Trials

The synthesized hydroxyapatite powder was mixed with naphthalene powder of 100-300 i m size in 1:3 w/w ratio and the powder-mix was subsequently cold-isostatically pressed with a compaction pressure of 160 MPa. Test samples and orbital implants (Fig.2) of different designs were turned from these blocks, which were further dried at 60[degrees]C for 200 hrs. and sintered at 1250[degrees]C for 4 hrs. The test samples were characterized in-vitro for different physical and mechanical properties. The prototypes of the orbital implant were sterilized by Pasteurization technique and subsequently exposed to 25 MRad aray radiation of [Co.sub.60] isotope to bring down the bacteria count to zero. The prostheses were implanted in the Mongrel dog to check the functional stability of the implant. Finally these prostheses were implanted to five anophthalmic human patients after enucleation / evisceration operation and post-operative studies are being continued.

[FIGURE 2 OMITTED]

RESULTS AND DISCUSSIONS

Chemical analysis of the hydroxyapatite powder through ICP technique revealed that the material was very pure, with non-toxic and biocompatible in nature. The results of the clinical, radiological and stoichiometric (having Ca/P molar ratio of 1.67) composition. XRD and IR-spectroscopy results also confirmed this observation. Examination of the injection site in mice and albino rabbit did not show any tissue reaction such as erythema, edema or necrosis of the bone, which indicated that the material was histological studies after bone grafting experiments in Mongrel dog and in human patients revealed the efficacy of the hydroxyapatite ceramics for filling traumatic or pathological bone defects or bone fracture as it always formed a bond between this material and the host bone within 6 weeks and the wound healing was complete within 14 weeks after the operation.

The physical and mechanical

properties of the test samples with equivalent porosity as that of the orbital implants are summarized in Table 1

The photographs taken after one week of implantation of the ocular implant in Mongrel dog revealed no sign of complication (Fig.3) and a good movement of the prostheses had been recorded. In addition, Fig.4 and 5 represents the photographs of the artificial eye of the first human patient taken after one month of the operation, which shows a very good degree of motility of the artificial eye-ball mimicking the movement of the fellow eye which confirms the findings of Colen et al. [6]

[FIGURES 3-5 OMITTED]

CONCLUSION

Though the degree of vasculerization of the surrounding tissues is yet to be established by MRI studies, the early motility of the orbital implants along with quick healing of the operation site indicates very good integration within the system. This new development is expected to revolutionize the treatment procedure after enucleation / evisceration surgery and rehabilitation of the anophthalmic human patients.

REFERENCES

[1.] Hench, L. L, Bioceramics: From concept to clinic, J. Am. Ceram. Soc., 74(7), 1487-510 (1991).

[2.] Shimizu, T., Zerwekh, J. E., Videman, T., et al., Bone ingrowth into porous calcium phosphate ceramics. Influence of pulsing electromagnetic field, J. Orthop. Res., 6, 248-259 (1988).

[3.] Dutton, J. J., Coraline hydroxyapatite as an ocular implant, Ophthalmology, 98, 370-377 (1991).

[4.] Sinha, M. K., Basu, D., Sen, P. S., Porous hydroxyapatite ceramic and its clinical applications, 49 (2), 102-104 (2000).

[5.] Osaka, A., Miura, Y., Takeuchi, K., Asada, M., Takahashi, K., Calcium apatite prepared from calcium hydroxide and orthophosphoric acid, J. Mats. Sc.: Mats. Med., 2, 51-55 (1991).

[6.] Colen, T. P., Paridaens, D. A., Lemij, H. G., Mourits, M. P., Van der Bosch, W. A., Comparison of artificial eye amplitudes with acrylic and hydroxyapatite spherical enucleation implants, Ophthalmology, 107, 1889-1894 (2000).

B. Kundu, M. K. Sinha and D. Basu

Central Glass and Ceramic Research Institute

Kolkata 700 032
Table 1: Final Properties

Composition Hydroxyapatite Porosity

Chemical Formula [Ca.sub.10][(P[O.sub.4]) Avg. Pore Size
 .sub.6][(OH).sub.2]

Theo. Density 3.17 g/c.c. Compressive Strength

Bulk Density 0.61 g/c.c. Wear factor under 1000 g
 load and sliding speed of
 30 m/min.

Total Wt. 2 g

Composition 75%

Chemical Formula 100-300 im

Theo. Density 5-10 MPa

Bulk Density 1.2 X [10-.sup.10]
 [cm.sup].2]/g
Total Wt.
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Article Details
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Author:Kundu, B.; Sinha, M.K.; Basu, D.
Publication:Trends in Biomaterials and Artificial Organs
Geographic Code:9INDI
Date:Jul 1, 2002
Words:1541
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