Conclusion and future perspectives

The primary aim of surface engineering of biomaterials is improving their biological performance by controlling over the interaction between the surface and living system. It is suggested that physicochemical cues of the surface are intrinsically linked revealing that the alteration of the surface topography will lead to localized changes in surface chemistry. Surface engineering methods usually are combined to obtain optimal results. For example, chemically non-reactive surface requires pre-activation via surface oxidation, functional groups introduction or ionizing irradiation for further surface grafting or biomolecules immobilization.
Non-specific protein deposition underlies all undesirable biological reactions and triggers other biomolecules and cell adhesion accounting for “biofouling”. PEG is considered as the “gold standard” in reducing bioadhesion and widely applied in anti-biofouling applications not only in biomedical applications but marine applications. However, PEG can suffer oxidative damage that limits its non-fouling feature for long-term applications[66]. Development of non-PEGylated hydrophilic surface with comparable protein-resistant property to PEGylated surface but better thermal and oxidative stability is of great interest. For example, dextran as a natural phosphorylcholines is studied as a PEG alternative for antifouling surface coating of biomaterials in long-term applications[1]. Zwitterionic polymers are another alternatives for antifouling surface modifications that exhibit even stronger hydration effect than PEG[66]. A curcumin loaded zwitterionic polymersome was incorporated in PDMS contact lenses to improve the antibiofouling and antimicrobial properties[9]. Bacteria acidify the local environment like tumor cells. Creation of stimuli-responsive antibacterial surface such as pH-sensitive can offer an on-demand strategy to address the resistant bacteria. Silver-releasing coatings are widely adopted due to their bactericidal ability. However, there are concerns arisen from their potential side effects to proteins. Such effects seem to be limited in applications with easy excretion of silver such as urinary catheters, or where the benefits outweigh the risk, such as skin wound dressings[3].
Thrombosis and intimal hyperplasia account to the major causes of blood-contacting device failure due to the unsatisfactory hemocompatibility. Achieving fully endothelialization on the luminal surface is termed as the ultimate solution for anti-coagulation. When designing proper surface of blood-contacting devices, the competitive growth of ECs and SMCs should be considered. Heparinization is a common accepted technique to enhance the antithrombogenicity of biomaterial. The mechanisms by which heparinized devices modulated those cellular behavior remains unclear. Possible reasons could be the interchanges between heparin and thrombospondin that impairs migration and proliferation of SMCs; and binding between heparin and angiogenesis growth factors that accelerates endothelialization[67]. Metallic implants are currently used in many hard tissue applications especially in load bearing conditions. Improving the tribology performance of biomaterials through surface coating can mitigate the abrasive debris and enhance the corrosion resistance. Super-lubricous coating offers a new perspective in surface engineered implants for articulating joint with relatively low wear generation.
Retaining the pluripotency in cell culture stage and maintaining the differentiated phenotype of stem cells are both critical. Stem cells can respond to the mechanical cues generated by the surface engineered substrate and convert them into biochemical cues. Biomolecules immobilization such as growth factors and peptides can provide direct biological cues to stem cells. Full-length proteins are prone to undergo conformational change and proteolytic degradation induced by surface properties. On the contrary, peptides are preferred owing to higher stability and easier control of surface density[68]. Intermediate crosslinker is favored to conjugate biomolecules to the surface due to the avoided direct contact between biomolecules and biomaterials. However, the mechanisms of interactions between cell and biomaterials surface are not fully defined yet since there are a few cell-ligand interactions identified as present. Moreover, the behavior of engineered surface can vary acrossin vitro and in vivo studies since living body presents a dynamic and more complex environment. For example, platelet adhesion to micropatterned surface can be mitigated in in vivo due to the hemodynamics. Which suggests that long-term in vivo effects of surface engineering are necessary to fully understand the performance of biomaterials.