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Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage and bone degradation. Medical therapies like glucosaminoglycan (GAG), chondroitin sulfate (CS), and hyaluronic acid (HA) aim to preserve joint function and reduce inflammation but may cause side effects when administered orally or via injection. Microneedle arrays (MNAs) offer a localized drug delivery method that reduces side effects. Thus, this study aims to demonstrate the feasibility of delivering GAG, CS, and HA using microneedles in vitro. An optimal needle geometry is crucial for the successful application of MNA. To address this, here we employ a multi-objective optimization framework using the non-dominated sorting genetic algorithm II (NSGA-II) to determine the ideal MNA design, focusing on preventing needle failure. Then, a three-step fabrication approach is followed to fabricate the MNAs. First, the master (male) molds are fabricated from poly(methyl methacrylate) using mechanical micromachining based on optimized needle geometry. Second, a micro-molding with Polydimethylsiloxane (PDMS) is used for the fabrication of production (female) molds. In the last step, the MNAs were fabricated by microcasting the hydrogels using the production molds. Light microscopy (LIMI) confirms the accuracy of the MNAs manufactured, and in vitro skin insertion tests demonstrate failure-free needle insertion. Subsequently, we confirmed the biocompatibility of MNAs by evaluating their impact on the L929 fibroblast cell line, human chondrocytes, and osteoblasts.

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PURPOSE: Design and evaluate a new micro-machining based approach for fabricating dissolvable microneedle arrays (MNAs) with diverse geometries and from different materials for dry delivery to skin microenvironments. The aims are to describe the new fabrication method, to evaluate geometric and material capability as well as reproducibility of the method, and to demonstrate the effectiveness of fabricated MNAs in delivering bioactive molecules. METHODS: Precise master molds were created using micromilling. Micromolding was used to create elastomer production molds from master molds. The dissolvable MNAs were then fabricated using the spin-casting method. Fabricated MNAs with different geometries were evaluated for reproducibility. MNAs from different materials were fabricated to show material capability. MNAs with embedded bioactive components were tested for functionality on human and mice skin. RESULTS: MNAs with different geometries and from carboxymethyl cellulose, polyvinyl pyrrolidone and maltodextrin were created reproducibly using our method. MNAs successfully pierce the skin, precisely deliver their bioactive cargo to skin and induce specific immunity in mice. CONCLUSIONS: We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo.

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BACKGROUND: Vibration analysis is a promising technique in diagnosing metabolic bone diseases such as osteoporosis and monitoring fracture healing. The aim of this study is to observe the structural dynamic property changes of the tibia extracted from the vibration analysis data. METHODS: In this study, bone mineral density and vibration measurements were made both in in vivo and in vitro conditions. The relationship between structural dynamic properties, obtained and bone mineral densities measured were investigated. Also, the effect of soft tissues on measured structural dynamic properties was analyzed. FINDINGS: Natural frequency of the tibia decreased with decreasing bone mineral density that presented a weak correlation with the bone mineral density values measured by dual energy X-ray densitometer of the femur. In the case of in vitro experiments, it was observed that the effect of muscles on measurement results is higher than that of the effect of the skin and the fibula which makes the modal identification procedure difficult. However, having very large percentage changes in the loss factors when mineral content and collagen are reduced is an encouraging result to believe that damping measurements may yield a promising technique in diagnosing progressing osteoporosis and monitoring fracture healing period. INTERPRETATION: The utilization of natural frequency alone as a diagnosing tool does not seem to be a sufficient method although there is a correlation between this parameter and bone mineral density. However, in vitro experiments showed that the identification of the loss factor is a promising technique in diagnosing progressing osteoporosis.

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