The Boston KPro, which is made primarily of PMMA is, as mentioned, vulnerable to infection. The device spans the cornea from the surface to the anterior chamber and is loosely held in place by corneal tissue. In many instances, anecdotally, sudden intraocular infection (endophthalmitis) can rapidly occur, especially after contact lens application or other manipulation that might push a bolus of bacteria into the eye. Bacterial endophthalmitis could result in total destruction and blindness of the eye. Such a calamity can happen particularly in autoimmune diseases (e.g., Stevens-Johnson syndrome, ocular pemphigoid, atopy) in which there is a tendency for tissue to melt that can lead to leakage around the KPro. Prophylaxis with topical antibiotics is very helpful28
but not completely protective. Additionally, poor compliance with such a regimen exacerbates the problem.
For all these reasons, any method that can enhance the adhesion of corneal tissue around the KPro on a long-term basis might reduce the incidence of infection. Alteration of the surface of the device to allow better biointegration could be of clinical benefit. Here we have modified the PMMA surface with HAp, which is widely used in orthopedic surgery and which has been proposed at least twice before as a KPro coating. Thus, Leon et al.29
implanted a penetrating type of KPro that was coated by coral HAp in a patient. Brittleness of the coral was cited as a problem, but it seems otherwise to have been well tolerated. Mehta et al.,13
when testing surfaces of various materials in tissue culture, found that HAp promoted superior keratocyte adhesion and proliferation.
We have modified a polymeric surface (PMMA) with HAp using three different approaches. The first was a previously reported method of forming HAp on PMMA by treatment with a concentrated base.17
The second was also a PMMA coating with polydopamine, and we used it to enhance HAp deposition.19
Deposition of HAp on polydopamine is initiated by the strong binding between calcium ion and the catechol group of dopamine.19,30
Polydopamine-based methods are advantageous in that they can be easily applied to numerous other substrates, because of the adhesive properties of polydopamine.18
The third method was an alternative approach. We formed a coating with polydopamine, which then readily binds the thiol group in 11-MUA.20
We added 11-MUA to polydopamine, resulting in the most uniform HAp coating on PMMA. The addition of 11-MUA might have further facilitated the HAp deposition process through the additional ionic interaction between calcium ions and the carboxyl groups on 11-MUA.
Biointegration involves the establishment of seamless physical connections between the tissue and the implant, which results in an increase in mechanical binding strength. Mechanical binding strength between the tissue and the implant has been used as an important measure of biointegration in orthopedic implants.31
However, in the case of prosthetic devices that interface with soft tissues (e.g., keratoprostheses), mechanical binding has not received much attention. Here, we have developed a simple method to measure the mechanical binding strength of an implant to the cornea. All HAp coatings not only enhanced cell viability on PMMA but also greatly increased the mechanical strength of binding of PMMA to corneal tissue ex vivo. This may be of benefit in preventing extrusion, particularly in response to trauma or transient increases in intraocular pressure. Ideally, this will reflect better tissue integrity and will translate to a lesser risk of bacterial translocation into the eye. PMMA itself is widely used and well tolerated as a KPro material; the fact that HAp coating did not adversely affect biocompatibility in vivo and appeared to reduce the inflammatory reaction to the PMMA is reassuring.
An important question is whether tissue adherence to substrates is caused by direct cell adhesion or by substrate interaction with the extracellular matrix (ECM), or both. A hybrid view is that the cells are crucial, though primarily insofar as they produce ECM. Here, we observed improved cell survival (which may require improved adhesion, but we did not demonstrate that rigorously such as by atomic force microscopy) in HAp-coated PMMA discs along with increased strength of adhesion. This study was not designed to address the contributions to adhesive properties from the ECM or how they compare with those from cells. It is also difficult to extrapolate findings from published reports because these mostly address integration with hard tissues such as bone and teeth.32
It is possible that the enhanced performance of the coated discs was caused by the accretion to HAp of proteins such as growth factors that promote cell adherence and ECM synthesis.33–35
Although the mechanism is unknown, these results are encouraging regarding the potential clinical applicability of HAp coatings in keratoprostheses. The technique shown here of measuring adhesion between tissue and KPro and thereby quantifying biointegration could be further applicable to a range of surfaces, including other inorganic compounds and metals as well as varying surface characteristics such as roughness and porosity. Findings of increased mechanical binding might well translate to tighter tissue adherence to the KPro and thereby reduce the risk for devastating infection. HAp coating of the Boston KPro stem now seems ready for clinical testing.
In conclusion, PMMA discs coated with HAp greatly improved cell viability, implant adhesion to tissue, and biocompatibility compared with unmodified PMMA.