In order to evaluate the biocompatibility of Mih keratoprosthesis in rabbit eyes, the PLA General Hospital conducted an animal experiment of Mih keratoprosthesis. Today, we will evaluate the biocompatibility of Mih keratoprosthesis based on the data of this experiment. In this study, Mihm artificial cornea was implanted into rabbit cornea, and the final conclusion was reached after 6 months of observation in Phase II.
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Evaluation of the biocompatibility of artificial cornea mainly includes four aspects
① Physical and chemical stability of materials
② Good organizational adaptability
③ Non toxic and non carcinogenic
④ No degradation in vivo
Mihm artificial cornea has passed the physical and chemical properties, cytotoxicity, muscle implantation experiments and other related biocompatibility tests. Therefore, this animal experiment aims to observe the histocompatibility of Mihm artificial cornea in the cornea through the in vivo experiment of animals, and further confirm the long-term stability and safety of Mihm artificial cornea.
At present, the optical parts of Boston keratoprosthesis and Mihm keratoprosthesis, which are widely used in clinical practice, are made of hard materials, while the fixation ring of the former, some kinds of rear discs and the stent of the latter are made of titanium materials, and the Mihm keratoprosthesis lens column is made of PMMA materials.
In the field of ophthalmology, PMMA is a commonly used material for corneal contact lenses, intraocular lenses, artificial eye pieces, etc. It has the advantages of stable properties, high transmittance, large refractive index, non degradation by biological oxidation reaction of the body, light biological reaction to the body, convenient processing, etc. It is an ideal optical material, and has been clinically proven to have good biocompatibility.
As the main component of the implanted cornea, the histocompatibility of titanium stent is an important factor for the stability of Mih keratoprosthesis. Titanium is widely used in biomedicine, especially in orthopedics, stomatology, plastic surgery and other clinical fields. Titanium has excellent biocompatibility and mechanical properties, good corrosion resistance and low price.
The above results prove that Mih artificial cornea has no degradation in vivo and has good tissue adaptability.
When medical materials are implanted into the human body, local tissues will have a "defense" reaction to foreign bodies, and white blood cells, lymphocytes and phagocytes will gather around the implants, causing acute inflammation of varying degrees.
According to the relevant requirements of biological evaluation of medical devices: when the biocompatibility of biomaterials is poor, and its residual toxic small molecules continue to leak out, it will stimulate local tissue cells to form chronic inflammation, even cancer, and the implants will also be wrapped to form a fibrous envelope; On the contrary, if the material is nontoxic and stable in performance, the capsule will become thinner over a long period of time, the lymphocytes in the capsule wall will disappear, and the capsule will become normal.
In this study, it was found that when the stent was implanted into the cornea of rabbits, only a slight foreign body reaction was triggered in the eyes of rabbits. The early symptoms were irritation and corneal edema, which lasted about 2 weeks and gradually subsided. In addition, neovascularization was significant at 2 weeks, corneal neovascularization was significantly increased at 4 weeks, most of which reached the center of the stent, and many deep neovascularization had been formed at 3-4 months.
Some people may ask: will the increase of new blood vessels not lead to adverse reactions? Actually not.
Moderate reaction occurs when the artificial cornea is implanted into the stroma, and the neovascularization is helpful to the local anti infection ability and anti dissolution. The experiment found that, in the whole process of corneal vascularization, the stent stably existed between corneal layers, the edema gradually subsided, there was no pathological damage such as exudation, necrosis, etc., no complications such as corneal dissolution and leakage, no corneal leukoplakia formation, the artificial corneal stent had no adverse effect on long-term corneal nutrition and metabolism, and had good biocompatibility.
At present, most researchers believe that, unlike corneal transplantation, artificial corneal stents often need good conditions for vascularized corneas in clinical applications. The neovascularized corneal implant bed is conducive to corneal surgery: it can provide a good microenvironment for cell proliferation and migration, promote cell proliferation and collagen synthesis, reduce corneal dissolution and the rejection rate of artificial corneas after surgery, and is conducive to the stable targeting of artificial corneas.
The research on corneal transplantation also shows that the existence of new blood vessels does not hinder tissue healing, on the contrary, granulation tissue in the early stage of healing accelerates the healing process. Transplantation rejection is only because the existence of new blood vessels provides a chance for donor antigens to contact host lymphocytes.
In the study, the clinical observation of 9 rabbits' eyes after Phase II operation lasted for 6 months, and the surface epithelium of all rabbits' eyes was basically healed 2-3 weeks after implantation of artificial corneal stent combined with cartilage reinforcement. Clinical observation showed that there was no acute inflammatory exudation and intraocular pressure was normal. During the whole observation period, there was no infection, no rejection, no tissue dissolution and leakage, no cartilage or stent exposure, and no looseness and fall off of the lens column, which proved that the clinical stability was high.
Pathological examination showed that the artificial cornea scaffold was complete, without displacement, tightly combined with the surrounding corneal tissue, and the fibroblasts were proliferating actively and flat, which increased its stability. There were only a few inflammatory cells and new blood vessels around the implant, but no fiber wrapping or foreign body granuloma formation was found. Compared with the contralateral eye, there was no phenomenon of corneal stroma dissolution and thinning. There was no obvious inflammatory reaction and change in other anterior segment and posterior segment structures. It should be known that the severity and duration of inflammatory reaction directly affect the stability of biomaterials.
All above prove that Mihm artificial cornea is non-toxic and carcinogenic.
After the artificial cornea is implanted, the tissue first reacts to the surgical trauma itself, and then the host's immune response to the implanted material.
In the stage of chronic inflammation, macrophages are important cells that regulate the immune and inflammatory responses between host and materials. In short, it depends on macrophages whether there will be immunity and inflammation during implantation.
Let's take a brief look at a series of manifestations of macrophages after intraocular keratoplasty.
After the artificial cornea is implanted in the body - the surface of the material adsorbs various proteins in the body fluid or blood - the adhesion protein on the surface of the macrophage recognition material - binds to the surface of the material - the macrophage attached to the surface of the material is activated to form foreign body giant cells - foreign body giant cells lead to fibrous encapsulation or material degradation and destruction - implantation failure.
Therefore, the activity of macrophages and the number of foreign body giant cells can also reflect the stability of implant materials.
Macrophages were not observed in the study, the implants were not expelled, and the cornea was not dissolved. The good corneal vascularization in the simple artificial corneal stent implantation group just shows this. Therefore, various factors released by moderate inflammatory reaction after artificial cornea implantation can promote angiogenesis, activate corneal cells and grow into scaffold pores, which is an important factor for maintaining stability of artificial cornea.
The above results prove that Mih artificial cornea has no degradation and high stability in vivo.
In addition, the scaffold is a material that needs to be integrated with the tissue. It directly contacts with the activated corneal cells, which are fibroblasts. Improving the surface microstructure of the artificial cornea can promote the proliferation of fibroblasts on the scaffold surface.
Therefore, the growth state of corneal fibroblasts is also an important indicator of histocompatibility in vivo. In this study, the histopathology of the two groups showed that more fibroblasts appeared in the corneal stroma 4 weeks later, which proved that the domestic artificial corneal scaffold material had good stability in the corneal tissue.
To sum up, Mihm artificial cornea material has high physical and chemical stability, good tissue adaptability, non-toxic, non carcinogenic and non degradable in vivo, and high biocompatibility.