Over the past half century, rapid progress has been made in laser-based medical diagnosis and treatment as well as in laser-based medical device fabrication. Lasers have unique capabilities for coating, machining, melting, polymerizing, sintering, and welding materials that are used in implantable and transdermal medical devices. In this review, academic and industrial developments involving laser processing of materials for dental, orthopedic, neural, ophthalmic, cardiovascular, and transdermal applications are described. In addition, laser processing of nanoscale materials for medical applications is discussed. Finally, challenges associated with commercialization of laser biomaterials are considered. Due to the unique capabilities provided by laser-based processes, it is anticipated that the use of laser biomaterials in implantable and transdermal medical devices will markedly increase over the coming years.

Micro- and nanostructures are found widely in nature and are important for the development and maintenance of organisms. Fabricated structures of dimensions corresponding to native biological structures may be obtained by methods such as laser-based fabrication and are of special relevance to applications in biology and medicine, as they impact cellular behavior. In this review, we will examine how fabricated structures of a particular length scale interact with natural structures of corresponding dimensions to produce the designed response, thus giving readers a primer on how laser-based fabrication may be fruitfully applied to biomedicine. Lasers have been used to fabricate nanopores for a variety of applications at the molecular level, such as the analysis of DNA. At the subcellular level, microstructures such as elastic beams fabricated by laser direct writing have been used to adhere and interact with cells. In the area of tissue engineering, an important application of micro- and nanostructures is related to their ability to control intercellular interactions. The fabricated structures facilitate the positioning of cells with respect to each other, so as to simulate the complexity of native tissues. Focused laser sources have also been used to create channels modified with functionalities to help guide cell migration.

Since the emergence of tissue engineering (TE), numerous researchers, particularly in the areas of materials, biological science, and engineering, have aimed to provide viable substitutes for the repair and regeneration of musculoskeletal and organ tissues. Bone TE has been extensively explored to mimic the anatomical geometry of bone with varied pore size distribution and varying mechanical properties in a radial direction (a functional gradient). This TE approach was explored to promote faster functional recovery of defective bones due to congenital, traumatic, or degenerative reasons. The present study integrated an appropriate additive manufacturing or rapid prototyping technique with automated computer-aided design models. This process was applied to the manufacture of a functionally graded scaffold (FGS). The FGS system takes into consideration both microscale anatomical geometries and mechanical properties of the native bone via an established porosity-stiffness relationship. Experimental verification of the FGS model was carried out by the fabrication of a femur bone segment using a selective laser sintering system. The physical femur model demonstrated good replication of the FGS structure that was generated. Future work aims to implement the FGS system for other musculoskeletal and organ tissues and integrate the current work with the authors’ in-house developed “computer aided system for tissue scaffolds” or CASTS system.

Rapid prototyping (RP) technologies, which are based on computer-aided design and computer-aided manufacturing, are widely employed in traditional industries. They are capable of achieving extensive and detailed control over the architecture of objects to be formed and therefore are increasingly used in the biomedical engineering field. Selective laser sintering (SLS), a versatile RP technique, uses a laser beam to selectively sinter powdered materials to form three-dimensional objects according to designs that can be based on data obtained from computer-based medical imaging technologies. In this article relating to biomedical applications, the principle, materials, machine modification, and parameter optimization for SLS are reviewed. Biomedical applications of SLS, especially in the fabrication of tissue engineering scaffolds and drug/biomolecule delivery vehicles, are presented and discussed. SLS exhibits great potential for many applications in biomedical engineering.

Laser-assisted bioprinting is one among several technologies that are being developed in the recent and growing field of bioprinting. Bioprinting is defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacology, and basic cell biology studies. We describe the physical parameters that need to be tuned for laser-assisted bioprinting of materials and cells, with high throughput and controlled printing resolution. We present its applications for printing cells and tissue-relevant biomaterials, both in vitro and in vivo. Finally, we discuss how this technique may help in reproducing the local cell micro-environment and dealing with tissue complexity and heterogeneity for fabricating functional tissue-engineered 3D constructs.

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.

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.

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.

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.

Advances in nanoscience and nanotechnology critically depend on the development of nanostructures whose properties are controlled during synthesis. We focus on this critical concept using semiconductor nanowires, which provide the capability through design and rational synthesis to realize unprecedented structural and functional complexity in building blocks as a platform material. First, a brief review of the synthesis of complex modulated nanowires in which rational design and synthesis can be used to precisely control composition, structure, and, most recently, structural topology is discussed. Second, the unique functional characteristics emerging from our exquisite control of nanowire materials are illustrated using several selected examples from nanoelectronics and nano-enabled energy. Finally, the remarkable power of nanowire building blocks is further highlighted through their capability to create unprecedented, active electronic interfaces with biological systems. Recent work pushing the limits of both multiplexed extracellular recording at the single-cell level and the first examples of intracellular recording is described, as well as the prospects for truly blurring the distinction between nonliving nanoelectronic and living biological systems.