Ryan D. Boehm

Multiphoton microscopy of transdermal quantum dot delivery using two photon polymerization-fabricated polymer microneedles.

Due to their ability to serve as fluorophores and drug delivery vehicles, quantum dots are a powerful tool for theranostics-based clinical applications. In this study, microneedle devices for transdermal drug delivery were fabricated by means of two-photon polymerization of an acrylate-based polymer. We examined proliferation of cells on this polymer using neonatal human epidermal keratinocytes and human dermal fibroblasts. The microneedle device was used to inject quantum dots into porcine skin; imaging of the quantum dots was performed using multiphoton microscopy.

Medical applications of diamond particles & surfaces

Diamond has been considered for use in several medical applications due to its unique mechanical, chemical, optical, and biological properties. In this paper, methods for preparing synthetic diamond surfaces and particles are described. In addition, recent developments involving the use of diamond in prostheses, sensing, imaging, and drug delivery applications are reviewed. These developments suggest that diamond-containing structures will provide significant improvements in the diagnosis and treatment of medical conditions over the coming years.

Modification of microneedles using inkjet printing

In this study, biodegradable acid anhydride copolymer microneedles containing quantum dots were fabricated by means of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing. Nanoindentation was performed to obtain the hardness and the Youngs modulus of the biodegradable acid anhydride copolymer. Imaging of quantum dots within porcine skin was accomplished by means of multiphoton microscopy. Our results suggest that the combination of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing enables fabrication of solid biodegradable microneedles with a wide range of geometries as well as a wide range of pharmacologic agent compositions.

Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles

Microneedles are needle-like projections with microscale features that may be used for transdermal delivery of a variety of pharmacologic agents, including antibacterial agents. In the study described in this paper, an indirect rapid prototyping approach involving a combination of visible light dynamic mask micro-stereolithography and micromolding was used to prepare microneedle arrays out of a biodegradable acid anhydride copolymer, Gantrez(®) AN 169 BF. Fourier transform infrared spectroscopy, energy dispersive x-ray spectrometry and nanoindentation studies were performed to evaluate the chemical and mechanical properties of the Gantrez(®) AN 169 BF material. Agar plating studies were used to evaluate the in vitro antimicrobial performance of these arrays against Bacillus subtilis, Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Large zones of growth inhibition were noted for Escherichia coli, S. aureus, Enterococcus faecalis and B. subtilis. The performance of Gantrez(®) AN 169 BF against several bacteria suggests that biodegradable acid anhydride copolymer microneedle arrays prepared using visible light dynamic mask micro-stereolithography micromolding may be useful for treating a variety of skin infections.

Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings

In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 μm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions.

Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays

Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition.

Microstereolithography-fabricated microneedles for fluid sampling of histamine-contaminated tuna

A custom-designed microneedle sampling system was prepared using dynamic mask microstereolithography; this sampling system was used for determination of histamine content in fresh, histamine-spiked, and spoiled tuna flesh. Lateral flow (test strip) assays were successfully utilized in the microneedle sampling system to assess histamine content. Good agreement was noted between data obtained from the microneedle sampling system and a commercially available histamine detection kit. A discrepancy was noted in the results from the microneedle sampling system and the commercially available histamine detection kit at low (negative) levels of histamine. There was an improvement in the agreement between the microneedle sampling system and the commercially available histamine detection kit at higher histamine levels. The results, which showed an improvement in the test duration and the amount of reagent needed for histamine detection, indicate the promise of printed microneedle sampling systems for histamine detection in seafood samples and other types of food testing.

Two-photon polymerization/micromolding of microscale barbs for medical applications

Tissue barbs are small-scale structures that may be used for sutureless joining of tissues. In this study, several types of tissue barbs were fabricated using two-photon polymerization/micromolding, including two-pronged tissue barbs, eight-pronged tissue barbs, 10-pronged tissue barbs, and 16-pronged tissue barbs. Tissue barb penetration in porcine tissue was observed using confocal laser scanning microscopy. Constructs containing medical tape and tissue barbs were created by applying tissue barbs in a parallel arrangement to Transpore™ medical tape. These results suggest that two-photon polymerization/micromolding is an indirect rapid prototyping approach that may be used for high-throughput replication of tissue barbs and other microstructured solid wound sealants.

1.7 Carbon and Diamond

This chapter focuses on the use of carbon materials in biomedical applications. Specifically, the use of pyrolytic carbon, diamond-like carbon (DLC), microcrystalline diamond, nanocrystalline diamond, and ultrananocrystalline diamond (UNCD) in medical applications is described. Pyrolytic carbon is a form of turbostratic carbon formed from pyrolysis of hydrocarbons or fullerene gases. DLC is an amorphous carbon material, which contains sp3-hybridized carbon atoms; in addition, it may contain a variable amount of hydrogen. Microcrystalline, nanocrystalline, and UNCD are composed of sp3-hybridized carbon crystals with microscale or nanoscale grain sizes. The structure, mechanical properties, biological properties, production processes, and biomedical applications of these carbon materials are addressed in detail. While the focus is placed on the use of these carbon materials in thin films and coatings, attention is also given to the general properties of carbon and its applications as a biomaterial.

CHAPTER 2:Biomimetic Materials and Surfaces in Detection

Biomimetic surfaces and materials may be utilized in biosensing applications, harnessing material properties that mimic the natural environment of a biomolecule in order to maintain its functionality, artificially create a complex that takes on the form of a biomolecular structure, or modify an environment to promote cellular affinity. Throughout the scientific literature, there are numerous mechanisms by which this concept may be accomplished. Synthetic lipid membranes, meant to mimic a cellular membrane, have been deposited onto sensor platforms for analyte detection with immobilized functional biomolecules. Natural biomolecules may also be immobilized on transducers, with care taken to protect their functionality (e.g., through polymer linkages), allowing them to operate as sensing units. Synthetic molecular constructs have been developed to mimic the activity of biomolecules. Molecularly imprinted polymers have been created, operating as artificial bioaffinity recognition sites for target molecules. Furthermore, whole cells may be immobilized onto sensing surfaces, acting as sensing units or mimics of larger tissue systems. In this chapter, the relevant literature examples are discussed, highlighting the means by which these biomimetic sensing approaches are accomplished.