Development of hyaluronic acid-silica composites via in situ precipitation for improved penetration efficiency in fast-dissolving microneedle systems.

Fast-dissolving microneedles (DMNs) hold significant promise for transdermal drug delivery, offering improved patient compliance, biocompatibility, and functional adaptability for various therapeutic purposes. However, the mechanical strength of the biodegradable polymers used in DMNs often proves insufficient for effective penetration into human skin, especially under high humidity conditions. While many composite strategies have been developed to reinforce polymer-based DMNs, simple mixing of the reinforcements with polymers often results in ineffective penetration due to inhomogeneous dispersion of the reinforcements and the formation of undesired micropores. In response to this challenge, this study aimed to enhance the mechanical performance of hyaluronic acid (HA)-based microneedles (MNs), one of the most commonly used DMN systems. We introduced in situ precipitation of silica nanoparticles (Si) into the HA matrix in conjunction with conventional micromolding. The precipitated silica nanoparticles were uniformly distributed, forming an interconnected network within the HA matrix. Experimental results demonstrated that the mechanical properties of the HA-Si composite MNs with up to 20 vol% Si significantly improved, leading to higher penetration efficiency compared to pure HA MNs, while maintaining structural integrity without any critical defects. The composite MNs also showed reduced degradation rates and preserved their drug delivery capabilities and biocompatibility. Thus, the developed HA-Si composite MNs present a promising solution for efficient transdermal drug delivery and address the mechanical limitations inherent in DMN systems. STATEMENT OF SIGNIFICANCE: HA-Si composite dissolving microneedle (DMN) systems were successfully fabricated through in situ precipitation and conventional micromolding processes. The precipitated silica nanoparticles formed an interconnected network within the HA matrix, ranging in size from 25 to 230 nm. The optimal silica content for HA-Si composite MN systems should be up to 20 % by volume to maintain structural integrity and mechanical properties. HA-Si composite MNs with up to 20 % Si showed improved penetration efficiency and reduced degradation rates compared to pure HA MNs, thereby expanding the operational window. The HA-Si composite MNs retained good drug delivery capabilities and biocompatibility.

Fouling mitigation in reverse osmosis processes with 3D printed sinusoidal spacers.

Feed spacers are an essential part of spiral wound modules for reverse osmosis (RO). They create flow channels between membrane sheets and manipulate hydrodynamic conditions to control membrane fouling. In this work, additive manufacturing (Polyjet) was used to print novel sinusoidal spacers with wavy axial filaments connected by perpendicular (ST) or slanted (SL) transverse filaments. When tested with 2 g/L NaCl solution, conventional and SL spacers had similar flux while the ST spacer had about 5-7% lower flux. The pressure losses for ST and SL spacers increased by up to 3 folds depending on the flow condition. In the colloidal silica fouling and biofouling tests, the sinusoidal spacers showed lower membrane permeability decrease of 46% for ST, 41% for SL vs 56% for conventional and 26% for ST, 22% for SL vs 33% for conventional, respectively. Optical coherence tomography images from colloidal silica fouling and confocal images from biofouling tests revealed that fouling patterns were closely associated with the local hydrodynamic conditions. Overall, sinusoidal spacers showed promising results in controlling membrane fouling, but there is potential for further optimizations to reduce channel pressure loss.

Freeform 3D printing of soft matters: recent advances in technology for biomedical engineering.

In the last decade, an emerging three-dimensional (3D) printing technique named freeform 3D printing has revolutionized the biomedical engineering field by allowing soft matters with or without cells to be printed and solidified with high precision regardless of their poor self-supportability. The key to this freeform 3D printing technology is the supporting matrices that hold the printed soft ink materials during omnidirectional writing and solidification. This approach not only overcomes structural design restrictions of conventional layer-by-layer printing but also helps to realize 3D printing of low-viscosity or slow-curing materials. This article focuses on the recent developments in freeform 3D printing of soft matters such as hydrogels, cells, and silicone elastomers, for biomedical engineering. Herein, we classify the reported freeform 3D printing systems into positive, negative, and functional based on the fabrication process, and discuss the rheological requirements of the supporting matrix in accordance with the rheological behavior of counterpart inks, aiming to guide development and evaluation of new freeform printing systems. We also provide a brief overview of various material systems used as supporting matrices for freeform 3D printing systems and explore the potential applications of freeform 3D printing systems in different areas of biomedical engineering.

Recyclable and biocompatible microgel-based supporting system for positive 3D freeform printing of silicone rubber.

Additive manufacturing (AM) of biomaterials has evolved from a rapid prototyping tool into a viable approach for the manufacturing of patient-specific implants over the past decade. It can tailor to the unique physiological and anatomical criteria of the patient's organs or bones through precise controlling of the structure during the 3D printing. Silicone elastomers, which is a major group of materials in many biomedical implants, have low viscosities and can be printed with a special AM platform, known as freeform 3D printing systems. The freeform 3D printing systems are composed of a supporting bath and a printing material. Current supporting matrices that are either commercially purchased or synthesized were usually disposed of after retrieval of the printed part. In this work, we proposed a new and improved supporting matrix comprises of synthesized calcium alginate microgels produced via encapsulation which can be recycled, reused, and recovered for multiple prints, hence minimizing wastage and cost of materials. The dehydration tolerance of the calcium alginate microgels was improved through physical means by the addition of glycerol and chemical means by developing new calcium alginate microgels encapsulated with glycerol. The recyclability of the heated calcium alginate microgels was also enhanced by a rehydration step with sodium chloride solution and a recovery step with calcium chloride solution via the ion exchange process. We envisaged that our reusable and recyclable biocompatible calcium alginate microgels can save material costs, time, and can be applied in various freeform 3D printing systems.