Bifunctional and Synergic Surface Modification of Biomedical Implants for Improved Biocompatibility

Abstract

Background: Development and fabrication of medical implants to monitor or treat the damaged or missing body part is becoming an important field of biomedicine because of increasing aged population which is more susceptible to chronic diseases. Tissue damage occurring during the implantation process, coupled with the prolonged presence of a foreign device within the body, can set off a series of reactions. These reactions, in turn, can culminate in the onset of foreign body responses, ultimately leading to a loss of functionality and potential implant failure. Damage to surrounding tissue during implantation, combined with the extended presence of foreign devices in the body, can trigger a cascade of events. These events may give rise to foreign body reactions that, in turn, result in the loss of implant functionality and potential implant failure. Historically, different techniques were employed to suppress inflammation and the formation of fibrous encapsulation around implants, with the goal of ensuring their sustained, long-term functionality. Nevertheless, these approaches often addressed only one facet of the problem, leaving the implants susceptible to disruption by other biological phenomena. Thus, there is a need to develop multifunctional biomedical devices comprising of different biomaterials which could synergically work and inhibit more than one biological activity. Objective: The objective of this study was to develop a multifunctional biomedical implant surface which had anti-coagulation, anti-thrombosis, anticorrosive and anti-material leaching properties. Methodology: A combination of passive and active modifications was proposed which could provide an anti-corrosive and anti-coagulant surface, respectively. First, different surface modifications including electropolishing, graphite coating and micropores formation were carried out and their hemocompatibility, anti-corrosive and anti-material leaching properties were compared and most suitable candidate was selected. Then, biological active modifications were fabricated to inhibit the thrombo-inflammatory cascades through pharmacological active ingredients. Novel ingredients from natural sources were embedded into different polymeric matrixes and their degradation, release kinetics, antioxidative potential and anticoagulation properties were compared and the most suitable candidate was selected. The mechanism of action of shortlisted candidate was predicted through the tools of bioinformatics and presence of pharmacological active ingredients responsible for inhibition of coagulation cascade were confirmed through GC- vi MS analysis. Afterwards, the passive and active modifications were combined, and their synergic effects were evaluated. Results: The findings suggest that graphite coatings exhibit favorable properties for both corrosion resistance and hemocompatibility. Atomic absorption analysis revealed no evidence of material leaching from the graphite-coated specimens. Following the coating process, the hydrophilicity of the graphite-coated samples improved, with the contact angle decreasing from 108° to 90.8°. This enhancement correlated with improved anticoagulant properties and reduced platelet adhesion compared to the uncoated surface. Hemocompatibility assessments showed a hemolysis potential of 1.09% for the coated specimens, in contrast to 1.8% for the uncoated ones. Moreover, the corrosion rate of the coated specimens was significantly lower than that of the bare specimens (1.4 mpy vs. 22 mpy). Leaching studies conducted under accelerated aging conditions provided no indication of redox reactions or material release from the coated specimens. In conclusion, physical vapor deposition (PVD)-based graphite coatings demonstrate promise in promoting antithrombotic and anti-leaching properties, making them a viable option for biomedical implant coatings. To develop innovative bioactive coatings, we incorporated drugs into a degradable matrix consisting of poly lactic acid (PLA) and chitosan separately, at various concentrations ranging from 1% to 15%. Additionally, we created a composite containing all three drugs, each at a 1% concentration. The outcomes revealed that all the samples initially released the drugs quickly, depending on their composition. Subsequently, they exhibited a sustained release pattern. However, chitosan-based matrices released the drugs and degraded faster compared to PLA-based ones. Furthermore, both sets of samples demonstrated good antioxidant and hemocompatibility properties as indicated by DPPH and hemolysis assays, with slightly better results for the PLA-based specimens. Consequently, we chose the PLA-based matrix for further investigation. The PLA-based matrix demonstrated notable anticoagulant properties, likely attributable to its interaction with key coagulation factors and proteins participating in the extrinsic pathway, including factor II, V, VII, and X. This conclusion finds support in our docking studies. The presence of anticoagulant components was confirmed through GC-MS analysis. In conclusion, the drug composite we proposed shows promise as a suitable candidate for biomedical implant coatings, offering potential benefits in terms of drug release control, biodegradability, and anticoagulation properties.Lastly, the graphite based passively modified surface was coated with PLA based active coating and resulting surface had excellent anti-coagulation, platelet adhesion inhibition, anti-corrosive and anti-material leaching properties which could potentially reduce the rate of adverse effects of medical device implantation and implant failure. Conclusion: In summary, the incorporation of natural drugs into graphite-based coatings offers a unique opportunity to enhance the anticoagulation, blood compatibility, and corrosion resistance characteristics of biomaterials. Given the ease of applying PVD-based modifications and polymeric coatings on a wide range of biomaterials, including polymers, ceramics, and metals, the approach presented in this study holds great promise as an innovative and efficient means to significantly improve the blood compatibility of biomedical devices and implants designed for blood contact. This breakthrough may pave the way for a more effective and practical approach in this regard.