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Abstract Chronic wounds present significant therapeutic challenges due to prolonged inflammation and bacterial infections, impeding healing. Conventional medicinal dressings typically deliver a single drug with a fixed release profile and lack responsiveness to variations in wound size, nature, or severity. This study introduces an innovative microneedle (MN) patch designed with different microneedle geometries and capable of dual‐drug delivery to address irregular wounds and complex therapeutic requirements. Utilizing CO₂ laser lithography, microneedle molds are fabricated with diverse geometries by precisely controlling laser parameters such as speed, power, and focus, achieving needle heights ranging from 162 ± 30 µm to 1570 ± 40 µm. The patch facilitates simultaneous delivery of simvastatin (SIM) for anti‐inflammatory and tetracycline hydrochloride (TH) for antibacterial properties, targeting different skin depths. In vitro diffusion studies confirm geometry‐dependent drug release profiles, with SIM achieving controlled release over three days and TH exhibiting sustained release over four days. Biocompatibility assays confirmed safety and enhanced fibroblast migration is noted in wound‐healing studies. Antimicrobial testing reveals a 99.9% reduction in bacterial viability. This cost‐effective and scalable approach enables precise, localized delivery and customization of MN arrays to match various wound geometries, offering a versatile platform for personalized medicine and improved chronic wound management. 

Abstract Conventional drug delivery methods often face challenges in terms of patient adherence and drug administration. Microneedles (MNs) patches have emerged as a promising alternative, offering a minimally invasive transdermal route for medications. However, their drug‐loading capacity remains limited, particularly for hydrophobic active pharmaceutical ingredients (APIs). Herein, microneedles are designed based on eutectic solvent gels (eutectogels) as transdermal carriers for hydrophobic APIs. A natural deep eutectic solvent (NADES) is combined to enhance the solubility of the hydrophobic APIs within the GelMA/PEGDA matrix for mechanical strength and sustained release from the resulting eutectogels microneedles (EU‐MNs). Using docetaxel, 5‐fluorouracil, and curcumin as hydrophobic APIs models, the superior drug‐loading capacity of the EU‐MNs is demonstrated. In vitro experiments revealed that the EU‐MNs provided a sustained release of distinct hydrophobic APIs over 4 days. Additionally, by properly adjusting the concentration and type of APIs, these microneedle patches do not exhibit cytotoxic effects on fibroblasts cell line (NIH/3T3), underscoring their potential for safe and effective transdermal drug delivery. These findings highlight the potential of EU‐MNs as versatile, eco‐friendly transdermal vehicles for large amounts of hydrophobic APIs, leading to more effective treatments for these drugs. 

Abstract Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life‐altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long‐term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose‐dependent and time‐limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi‐electrode array that measures real‐time electrophysiological responses at 32 spatially‐distinct locations. Irradiation at 27 µW mm⁻²results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through “on” and “off” light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed‐loop systems for cardiac regulation and intervention, for example, in the context of arrythmias. 

Abstract Scalable processes are requisite for the robust biomanufacturing of human pluripotent stem cell (hPSC)‐derived therapeutics. Toward this end, we demonstrate the xeno‐free expansion and directed differentiation of human embryonic and induced pluripotent stem cells to definitive endoderm (DE) in a controlled stirred suspension bioreactor (SSB). Based on previous work on converting hPSCs to insulin‐producing progeny, differentiation of two hPSC lines was optimized in planar cultures yielding up to 87% FOXA2⁺/SOX17⁺cells. Next, hPSCs were propagated in an SSB with controlled pH and dissolved oxygen. Cultures displayed a 10‐ to 12‐fold increase in cell number over 5–6 days with the maintenance of pluripotency (>85% OCT4⁺) and viability (>85%). For differentiation, SSB cultures yielded up to 89% FOXA2⁺/SOX17⁺cells or ~ 8 DE cells per seeded hPSC. Specification to DE cell fate was consistently more efficient in the bioreactor compared to planar cultures. Hence, a tunable strategy is established that is suitable for the xeno‐free manufacturing of DE cells from different hPSC lines in scalable SSBs. This study advances bioprocess development for producing a wide gamut of human DE cell‐derived therapeutics.