Introducing micro- and nanoscale features on biomaterials in an engineered, controlled manner has been shown to positively affect medical implant integration into the human body. A key factor in this process is the initial cellular response toward the implant. Different techniques such as chemical treatment, plasma spraying, lithography, and coatings, among others, have been applied during the last decades to improve the implant integration. One of the methods that started to be recently exploited is laser surface engineering (LSE). LSE offers a wide range of new surface engineering methods, such as laser surface melting (LSM), laser engineered net shaping (LENS), and selective laser melting/sintering (SLM/S) that can generate complex micro- and nanoscale features with high resolution. This review provides an overview of the initial cellular response to medical implants and the different techniques used to modify the surface of different biomaterials. An emphasis is given to laser techniques that were recently developed for surface texturing, describing in vitro, pre-clinical, and clinical trials performed thus far.

In recent years, biomaterial investigators have increasingly focused their research on hydrogels and their capability to be fabricated into tissue engineering scaffolds. Although several fabrication methods have been used to produce hydrogel scaffolds, those methods are unable to routinely produce three-dimensional submicron and nanoscale scaffolds with precise control of the geometry, a crucial factor necessitated by the recent developments in the field of tissue engineering. Femtosecond laser-induced two-photon polymerization is a promising technique that fulfills these requirements. In our work, we used a femtosecond laser to fabricate three-dimensional submicron-scale scaffolds with poly(ethylene glycol) (PEG). The modulus, dimensions, and shape of the scaffold can be readily adjusted by changing both the laser parameters and the molecular weight of the PEG prepolymer. With the femtosecond laser, we also fabricated two-dimensional topographical patterns, which have important applications in basic biological research. To improve the throughput of femtosecond laser fabrication, we integrated the femtosecond direct-write process with a nano-imprint process by which the femtosecond laser is used to produce nano-patterned molds. We then carried out nanoimprinting to transfer the nanofeatures in the mold to the hydrogel in a massively parallel fashion.

Controlling the spatial arrangement of biomaterials, including living cells, with high resolution (±5 μm) provides the foundation for fabricating complex biologic systems for studies ranging from the fundamentals of cell-cell and cell-matrix interactions to applications in tissue engineering. However, the level of spatial control required cannot be obtained through conventional cell processing techniques (e.g., pipetting of or even ink-jetting cells), as they lack the precision, reproducibility, and speed required for the rapid fabrication of idealized engineered constructs. Laser direct-write approaches (e.g., matrix-assisted pulsed-laser evaporation direct-write [MAPLE DW]), previously employed for the rapid prototyping of electronics, have shown reliable patterning of biomaterials with a spatial resolution of ±5 μm. Moreover, recent advances allow the rapid, precise deposition of viable mammalian cells and pluripotent stem cells on well-defined substrates, enabling the laser direct-writing platform to advance manipulation of the in vitro cellular microenvironment (e.g., the stem cell niche). Herein, we review the mechanisms and recent advances demonstrating the versatility and biofabrication potential of one particular laser-based technique, MAPLE DW.

Microchips have revolutionized biological analysis since they can be used to perform biochemical analysis with high efficiency and accuracy. Femtosecond laser direct writing followed by wet chemical etching can be used to fabricate hollow microstructures with almost any three-dimensional (3D) structure without stacking or bonding. This permits microfluidic systems to be integrated with micro-optical components (e.g., mirrors and lenses) and micromechanical components (e.g., valves and pumps) in a glass chip by a single continuous process. Furthermore, other micro-optical components such as optical waveguides and attenuators can be integrated by additional femtosecond laser direct writing. Thus, femtosecond laser direct writing can be used to fabricate functional microfluidics, optofluidics, lab-on-a-chip devices, and micro-total analysis systems. In this study, 3D femtosecond laser micromachining is used to fabricate microchips integrated with functional microcomponents for biological analysis. Optofluidic systems, in which microfluidic components are integrated with micro-optical components, are used to detect single cells and perform high-sensitivity analysis of liquid samples by optical methods. Another interesting microchip is introduced, namely nanoaquariums, which is used for performing dynamic observations of microorganisms and bacteria and allows the functions of microorganisms and bacteria to be determined, such as elucidation of the gliding mechanism of Phormidium to seedling roots for growth acceleration of vegetables.