Enhancing osseointegration and mitigating bacterial biofilms on medical-grade titanium with chitosan-conjugated liquid-infused coatings.

Titanium alloys, in particular, medical-grade Ti-6Al-4 V, are heavily used in orthopaedic applications due to their high moduli, strength, and biocompatibility. Implant infection can result in biofilm formation and failure of prosthesis. The formation of a biofilm on implants protects bacteria from antibiotics and the immune response, resulting in the propagation of the infection and ultimately resulting in device failure. Recently, slippery liquid-infused surfaces (LIS) have been investigated for their stable liquid interface, which provides excellent repellent properties to suppress biofilm formation. One of the current limitations of LIS coatings lies in the indistinctive repellency of bone cells in orthopaedic applications, resulting in poor tissue integration and bone ingrowth with the implant. Here, we report a chitosan impregnated LIS coating that facilitates cell adhesion while preventing biofilm formation. The fabricated coating displayed high contact angles (108.2 ± 5.2°) and low sliding angles (3.56 ± 4.3°). Elemental analysis obtained using X-ray photoelectron spectroscopy (XPS) confirmed the availability of fluorine and nitrogen, indicating the presence of fluorosilane and chitosan in the final coating. Furthermore, our results suggest that chitosan-conjugated LIS increased cell adhesion of osteoblast-like SaOS-2 cells and significantly promoted proliferation (a fourfold increase at 7-day incubation) compared to conventional titanium liquid-infused surfaces. Furthermore, the chitosan conjugated LIS significantly reduced biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) by up to 50% and 75% when compared to untreated titanium and chitosan-coated titanium, respectively. The engineered coating can be easily modified with other biopolymers or capture molecules to be applied to other biomaterials where tissue integration and biofilm prevention are needed.

Antibiotic-Impregnated Liquid-Infused Coatings Suppress the Formation of Methicillin-Resistant Staphylococcus aureus Biofilms.

Medical device-associated infections are an ongoing problem. Once an implant is infected, bacteria create a complex community on the surface known as a biofilm, protecting the bacterial cells against antibiotics and the immune system. To prevent biofilm formation, several coatings have been engineered to hinder bacterial adhesion or viability. In recent years, liquid-infused surfaces (LISs) have been shown to be effective in repelling bacteria due to the presence of a tethered liquid interface. However, local lubricant loss or temporary local displacement can lead to bacteria penetrating the lubrication layer, which can then attach to the surface, proliferate, and form a biofilm. Biofilm formation on biomedical devices can subsequently disrupt the chemistry tethering the slippery liquid interface, causing the LIS coating to fail completely. To address this concern, we developed a "fail-proof" multifunctional coating through the combination of a LIS with tethered antibiotics. The coatings were tested on a medical-grade stainless steel using contact angle, sliding angle, and Fourier transform infrared spectroscopy. The results confirm the presence of antibiotics while maintaining a stable and slippery liquid interface. The antibiotic liquid-infused surface significantly reduced biofilm formation (97% reduction compared to the control) and was tested against two strains of Staphylococcus aureus, including a methicillin-resistant strain. We also demonstrated that antibiotics remain active and reduce bacteria proliferation after subsequent coating modifications. This multifunctional approach can be applied to other biomaterials and provide not only a fail-safe but a fail-proof strategy for preventing bacteria-associated infections.

Biofunctional Lubricant-Infused Vascular Grafts Functionalized with Silanized Bio-Inks Suppress Thrombin Generation and Promote Endothelialization.

The ongoing problem with the thrombogenicity and poor tissue integration of synthetic vascular grafts demands the design of new surfaces that simultaneously suppress thrombosis and promote endothelialization. Lubricant-infused surfaces have shown outstanding results in preventing clot formation; however, their innate ability to completely block the surface, averts targeted binding of desired biomolecules. We report a new class of expanded polytetrafluoroethylene (ePTFE) vascular grafts that prevent blood coagulation and concurrently promote endothelial cell adhesion. This is made possible by direct silanization of anti-CD34 antibody with the coupling agent and subsequent conjugation of the silanized antibody to the ePTFE surface. In contrast to the conventional methods, we eliminated the need to chemically modify the ePTFE substrate for attaching the capturing ligand, and as a result preserved the innate surface properties of the ePTFE substrate. This is crucial for infiltrating the fluorine-based ePTFE substrate with a biocompatible perfluorocarbon-based lubricant and ultimately creating a functional and stable lubricant-infused layer. Compared to commercially available ePTFE vascular grafts and the ones coated using conventional methods, our developed ePTFE grafts significantly attenuate thrombin generation and blood clot formation and specifically capture endothelial cells from human whole blood while preventing nonspecific adhesion of undesirable proteins and cells. The developed technology can be applied to other biomarkers and biomaterials and can be tailored toward different biomedical applications where biofunctionality and targeted binding are of importance.