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Three-dimensional (3D) printing is implemented for surface modification of titanium alloy substrates with multilayered biofunctional polymeric coatings. Poly(lactic-coglycolic) acid (PLGA) and polycaprolactone (PCL) polymers were embedded with amorphous calcium phosphate (ACP) and vancomycin (VA) therapeutic agents to promote osseointegration and antibacterial activity, respectively. PCL coatings revealed a uniform deposition pattern of the ACP-laden formulation and enhanced cell adhesion on the titanium alloy substrates as compared to the PLGA coatings. Scanning electron microscopy and Fourier-transform infrared spectroscopy confirmed a nanocomposite structure of ACP particles showing strong binding with the polymers. Cell viability data showed comparable MC3T3 osteoblast proliferation on polymeric coatings as equivalent to positive controls. In vitro live/dead assessment indicated higher cell attachments for 10 layers (burst release of ACP) as compared to 20 layers (steady release) for PCL coatings. The PCL coatings loaded with the antibacterial drug VA displayed a tunable release kinetics profile based on the multilayered design and drug content of the coatings. Moreover, the concentration of active VA released from the coatings was above the minimum inhibitory concentration and minimum bactericidal concentration, demonstrating its effectiveness against Staphylococcus aureus bacterial strain. This research provides a basis for developing antibacterial biocompatible coatings to promote osseointegration of orthopedic implants. 

The interaction between bone morphogenetic protein-2 (BMP-2) and the surface of biomaterials is essential for the restoration of bone and cartilage tissue, inducing cellular differentiation and proliferation. The properties of the surface, including topology features, regulate the conformation and bioactivity of the protein. In this research, we investigated the influence of nanopatterned surfaces on the interaction of a homodimer BMP-2 with graphite material by combining molecular dynamics (MD) and steered molecular dynamics (SMD) simulations. The graphite substrates were patterned as flat, linear grating, square, and circular profiles in combination with BMP-2 conformation in the side-on configuration. Ramachandran plots for the wrist and knuckle epitopes indicated no steric hindrances and provided binding sites to type I and type II receptors. Results showed two optimal patterns that increased protein adsorption of the lower monomer while preserving the secondary structure and leaving the upper monomer free to interact with the cells. Charged residues arginine and lysine and polar residues histidine and tyrosine were the main residues responsible for the strong interaction with the graphite surface. This research provides new molecular-level insights to further understand the mechanisms underlying protein adsorption on nanoscale patterned substrates. 

Drug delivery through the skin offers many advantages such as avoidance of hepatic first-pass metabolism, maintenance of steady plasma concentration, safety, and compliance over oral or parenteral pathways. However, the biggest challenge for transdermal delivery is that only a limited number of potent drugs with ideal physicochemical properties can passively diffuse and intercellularly permeate through skin barriers and achieve therapeutic concentration by this route. Significant efforts have been made toward the development of approaches to enhance transdermal permeation of the drugs. Among them, microneedles represent one of the microscale physical enhancement methods that greatly expand the spectrum of drugs for transdermal and intradermal delivery. Microneedles typically measure 0.1–1 mm in length. In this review, microneedle materials, fabrication routes, characterization techniques, and applications for transdermal delivery are discussed. A variety of materials such as silicon, stainless steel, and polymers have been used to fabricate solid, coated, hollow, or dissolvable microneedles. Their implications for transdermal drug delivery have been discussed extensively. However, there remain challenges with sustained delivery, efficacy, cost-effective fabrication, and large-scale manufacturing. This review discusses different modes of characterization and the gaps in manufacturing technologies associated with microneedles. This review also discusses their potential impact on drug delivery, vaccine delivery, disease diagnostic, and cosmetics applications. 

Understanding the deformation behavior during nanoimprint lithography is crucial for high resolution patterning. Molecular dynamics modeling was implemented to investigate the effect of different mold profiles (cylindrical, rectangular, and spherical) on the von Mises stress, lattice dislocations, and material deformation. Relatively higher von Mises stress (1.08 × 107 Pa) was observed for the spherical mold profile compared to the rectangular and cylindrical profiles due to the larger surface area of contact during the mold penetration stage of NIL. Substantial increases in the von Mises stress were observed for all the mold geometries during the mold penetration stage. The von Mises stresses had a reduction in the relaxation and mold retrieval stages based on the rearrangement of the gold atoms. The lattice dislocation during the deformation process revealed the formation of the BCC structure which further reverted to the FCC structure after the mold retrieval. The polyhedral template matching (PTM) method was used to explain the retention of the FCC structure and subsequent ductile behavior of the substrate. The cylindrical mold had the lowest percentage spring back in both of the orthogonal directions and thus replicated the mold profile with high-fidelity as compared to the spherical and rectangular molds. The findings of this research can aid the design of molds for several applications. 

Microneedles provide a transdermal pathway for drug delivery, cosmetic infusion, vaccine administration, and disease diagnostics. Microneedle fabrication relies on the interplay of several variables which include design parameters, material properties, and processing conditions. In this research, our group explores the effect of design parameters and process variables for laser ablation of microneedles within a Polymethyl methacrylate (PMMA) mold. An Ytterbium laser (200W) was utilized to study the effect of five inputs factors (laser power, pulse width, number of repetitions, laser waveform, and interval time between laser pulses) on two output factors (diameter and height) of the fabricated microneedles. Polydimethylsiloxane (PDMS) polymer was cast within the PMMA microneedle mold. Scanning electron microscopy (SEM) was employed to image topographical features of the microneedles. Further, mechanical testing of the microneedles was conducted to evaluate the buckling load and deformation behavior of the microneedle array. A 20W pulse laser with trapezoidal waveform resulted in optimal microneedle topography with an aspect ratio of 1.2. ANOVA results (α = 0.05) depicted that laser power and number of repetitions were significant factors determining the geometrical features of the microneedle array. This research establishes a framework for the design and manufacturing of customized microneedles for precision medicine. 

This research investigates deformation behavior of polystyrene (PS) as a thermoplastic resist material for the thermal nanoimprint lithography (T-NIL) process. Molecular dynamics modeling was conducted on a PS substrate with dimensions 58 × 65 × 61 Å that was imprinted with a rigid, spherical indenter. The effect of indenter size, force, and imprinting duration were evaluated in terms of indentation depth, penetration depth, recovery depth, and recovery percentage of the polymer. The results show that the largest indenter, regardless of force, has the most significant impact on deformation behavior. The 40 Å indenter with a 1 µN of force caused the surface molecules to descend to the lowest point compared to the other indenters. An increase in indenter size resulted in higher penetration depth, recovery depth, and recovery percentage. Higher durations of imprint cycle (400 fs) resulted in plastic deformation of the PS material with minimal recovery (4 Å). The results of this research lay the foundation for explaining the effect of several T-NIL process parameters on virgin PS thermoplastic resist material.