Abstract The advancement of wound dressing technology has been significantly enhanced by the development of microneedles composed of hyaluronic acid (HA) and polyvinyl alcohol (PVA). This study aims to fabricate HA-PVA microneedles with varying HA concentrations (0.5%, 1%, 1.5%, and 2%) to improve wound care through effective drug delivery with minimal invasiveness to the skin. Fourier-transform infrared (FT-IR) spectroscopy confirmed the successful formation of a stable, cross-linked hydrogel network between HA and PVA. Fluorescence microscopy demonstrated the ability of these microneedles to effectively penetrate porcine skin and provide controlled drug release. Experimental results indicated that increasing HA concentration enhanced drug release efficiency and antibacterial properties, However, it also increased water absorption and swelling behavior, which impacted the mechanical integrity of the microneedles. Notably, microneedles with 2% HA concentration exhibited the optimal balance among drug permeation in skin diffusion tests, structural stability, and antibacterial efficacy. These findings underscore the promising potential of HA-PVA microneedles as an advanced platform for wound dressing applications, offering a minimally invasive, efficient, and multifunctional approach to targeted drug delivery and infection prevention.

Keywords: Hyaluronic acid, Poly vinyl alcohol, Microneedle, Wound healing, Biomaterials

Funding: The authors are grateful for the research funding provided by Faculty of Engineering, Khon Kaen University under the Research Scholarship for M.Eng. Students project under Contract Nos.M-Eng.-CHE.-007/2568.

Citation:  Suwatsrisakun, N., Prungruan, C., and Tanangteerapong, D. 2026. Development of hyaluronic acid incorporated with polyvinyl alcohol for wound microneedle application. Natural and Life Sciences Communications. 25(3): e2026048.

Graphical Abstract:

INTRODUCTION

The advancement of biomaterial-based wound dressings has emerged as a pivotal focus in regenerative medicine, particularly in developing functional platforms that combine moisture retention, mechanical durability, and precise drug release capabilities for effective skin repair (Deng et al., 2022; Joshi et al., 2025). Among the vast array of biomaterials, biopolymeric hydrogels have demonstrated substantial potential due to their biocompatibility, tunable physical properties, and ability to mimic the extracellular matrix (ECM) (Papakonstantinou et al., 2012). In this context, hyaluronic acid (HA) and polyvinyl alcohol (PVA) have garnered significant attention as complementary materials suitable for fabricating advanced hydrogel systems for wound healing and transdermal applications (Kodavaty, 2022).

HA, a key ECM component, is a naturally occurring glycosaminoglycan known for its superior hydrophilicity, viscoelasticity, and ability to stimulate cellular functions essential for wound healing such as keratinocyte proliferation and fibroblast migration (Baniasadi, 2025; Ye et al., 2025). PVA, on the other hand, is a synthetic biomaterial extensively used in biomedical engineering due to its non-toxicity, high water-absorbency, and excellent film-forming ability (Liang et al., 2024). The presence of hydroxyl groups on PVA facilitates intermolecular hydrogen bonding with HA, enabling the formation of a robust and stable hydrogel network (Kim et al., 2011; Fahmy et al., 2015; Khunmanee et al., 2017). This crosslinked matrix offers mechanical reinforcement and chemical stability, both critical for sustained performance in wound environments (Thang et al., 2023; Ribeiro et al., 2024).

Importantly, the crosslinking between HA and PVA creates a synergistic hydrogel composite with enhanced swelling behavior, water retention, and drug diffusion control, making it highly suitable for minimally invasive drug delivery systems (Torres-Figueroa et al., 2023). Such hydrogel matrices are increasingly integrated into microneedle (MN) platforms, which can bypass the stratum corneum and enable targeted delivery of therapeutic agents to deeper skin layers without significant pain or tissue disruption. In our formulation, guar gum is incorporated as a natural thickening and stabilizing polymer that enhances viscosity, improves mold filling, and contributes to mechanical cohesiveness of the microneedle matrix. Acetic acid serves as a mild acidifying agent that facilitates polymer dispersion and assists in the uniform hydration and dissolution of guar gum, thereby improving solution homogeneity prior to casting. These additives are essential for ensuring structural stability and achieving reproducible microneedle formation, which have not been sufficiently addressed in earlier reports.

To evaluate drug permeation, crystal violet dye was employed as a model compound. Although not a therapeutic agent, this dye offers a simple, visible, and quantifiable indicator of microneedle-mediated diffusion through porcine skin. This approach is a widely accepted preliminary method in microneedle development to optimize structural and release properties before loading active drugs.

While HA-PVA microneedle systems have been previously investigated, notably by Li et al. (2024), who demonstrated antibacterial, anti-inflammatory, and antioxidant effects for diabetic wound healing, our study differentiates itself by focusing on the impact of varying HA concentrations on mechanical properties, swelling behavior, skin permeation characteristics, and antibacterial efficacy. Unlike Li et al., whose study emphasized the effects of bioactive additives, this work systematically explores how HA content alone governs key physical and functional parameters necessary for designing optimized microneedle wound dressings.

This study aims to develop HA-PVA-based microneedle arrays as next-generation bioactive wound dressings, employing a polydimethylsiloxane (PDMS) mold casting technique for fabrication. By engineering a well-defined crosslinked architecture, these microneedles are expected to achieve effective skin penetration, controlled release of therapeutic agents, and retention of water and antimicrobial properties at the wound interface. Moreover, the HA-PVA system demonstrates biomaterial versatility by combining biodegradability, structural integrity, and localized drug delivery potential, aligning well with modern therapeutic demands in chronic and deep wound management.

MATERIALS AND METHODS

Materials

Hyaluronic acid (Size small, Molecular weight: Average 10,000 Daltons, purity ≥95%), Guar gum (food/analytical grade) and Microneedle mold (25 x 15 mm, H600μm, 10 x 10, S600μm, D300μm, Conical) from MySkinRecipes (Bangkok, Thailand). Polyvinyl alcohol (PVA, grade 117, fully hydrolyzed, purity ≥91.5%) and Acetic acid (≥99.7%, analytical grade) from RCI Labscan (Bangkok, Thailand).

Methods

Preparation of cross-links HA-PVA

10 g of polyvinyl alcohol (PVA) was dissolved in 100 ml of deionized (DI) water at 90°C for 30 minutes. Once the PVA had been completely dissolved, hyaluronic acid (HA) was added in concentrations of 0.5%, 1%, 1.5%, and 2% (w/v), respectively. The mixture was stirred for an additional 10–15 minutes to ensure thorough blending. The mixture was then placed in an oven set at 50°C for 1 hour to promote physical crosslinking through intermolecular hydrogen bonding between HA and PVA chains.

Preparation of HA-PVA Microneedle

0.3 g of ascorbic acid and 2 g of guar gum (a viscous polymer powder) were dissolved in 10 ml of 1% (v/v) acetic acid, then stirred until fully mixed. To ensure a uniform and impurity-free solution, 10 ml of this solution was filtered and further stirred to achieve complete homogeneity. After that, the solution was combined with the previously prepared HA-PVA solution and poured into PDMS molds, allowing improved mold filling and structural stability during fabrication. The molds were then stored at 2°C for 2 hours. This process resulted in fully formed HA-PVA microneedles with enhanced polymer stability and viscosity provided by ascorbic acid and guar gum (Zhang et al., 2018).

Fourier transform infrared spectroscopy (FTIR)

The chemical properties of the hydrogel were measured using an FTIR spectrophotometer, and the spectra were recorded in the wavelength range of 4,000-500 cm⁻¹ at 25°C (Kim et al., 2011).

Swelling rate test

The swelling behavior of the HA-PVA hydrogel membrane was analyzed by immersing a dry sample measuring 25 mm × 15 mm in distilled water at room temperature. Although biological buffers such as phosphate-buffered saline (PBS) can better mimic physiological pH conditions, distilled water was selected in this study to provide a controlled and simplified environment to assess intrinsic swelling characteristics without interference from ions or salts. The dry weight (W_i) was recorded after the membrane had been kept in a vacuum at room temperature for 6 hours. The swollen weight (W_f) was measured after the membrane had been soaked in distilled water for a specified period (Kim et al., 1992). The water swelling percentage was calculated by using the following equation:

Swelling ratio (%) = W_f - W_i / W_i ×100                         (1)

W_i = initial weight of the sample

W_f = weight after immersion in the liquid

Micro universal testing machine (UTM)

The samples are prepared in standardized shapes, such as dog-bone or rectangular forms, and their moisture content is ensured to be uniform. They are mounted in a Universal Testing Machine (UTM) with calibrated grips. Testing parameters are set, and the samples are pulled until they break, with force and displacement data being recorded. The data is analyzed to determine tensile strength (Bai et al., 2018). Multiple tests are conducted for consistency, with safety protocols, temperature, and moisture being controlled.

Drug release study

A model drug (crystal violet) was selected due to its vivid color, ease of visualization, and common use as a surrogate marker for preliminary release and permeation assessments (Vrdoljak et al., 2016). A total of 1 g of crystal violet was incorporated into the HA-PVA microneedles during fabrication. The 10×10 microneedle patches were then applied to freshly excised porcine skin obtained from the abdominal region, which was cleaned, shaved, and hydrated in phosphate-buffered saline (PBS, pH 7.4) at room temperature prior to testing. The patches were pressed onto the skin for 30, 60, 90, and 120 minutes to evaluate time-dependent dye release and skin penetration. PBS was selected as the hydration medium due to its physiological relevance and chemical inertness toward the HA–PVA hydrogel system; no chemical interference between PBS components and crystal violet was expected under the experimental conditions (Vrdoljak et al., 2016).

After removal of the microneedle patches, the formation of discrete violet dot patterns on the skin surface was visually examined. These patterns correspond to the microchannels created by microneedle insertion and indicate successful permeation of the dye into the skin layers. The permeation behavior was evaluated qualitatively based on color intensity and spatial distribution of the dye, serving as a preliminary assessment of microneedle-mediated release prior to quantitative drug loading.

Antibacterial test

The test using the Disc Diffusion technique involves preparing agar plates filled with Mueller-Hinton agar and ensuring a smooth, even surface. Then, gram-positive Staphylococcus aureus and gram-negative Escherichia coli bacteria are cultured on the agar plate until it is fully covered. Next, cut samples with a diameter of 6-8 mm are placed on the agar plate using forceps (Balouiri et al., 2015), ensuring an appropriate distance between them. The plate is then covered with a lid and incubated at 37°C for 24 hours (Kim et al., 1992). After the incubation period, the radius of the clear zone around the sample is measured to assess the antibacterial effectiveness, and the test results are summarized.

RESULTS

FT-IR (Fourier transform infrared spectrometer)

The FT-IR spectrum analysis in Figure 1 revealed characteristic peaks of hyaluronic acid (HA) and polyvinyl alcohol (PVA), confirming their functional groups. HA showed prominent absorption between 3,600–2,900 cm⁻¹ due to hydroxyl (-OH) groups, key to its water retention, and peaks around 2,900–2,800 cm⁻¹ and 1,600 cm⁻¹ linked to amine (-NH) groups and water absorption capacity (Liang et al., 2024). PVA exhibited a strong peak at 1,633 cm⁻¹ indicating unreacted hydroxyl groups and peaks at 2,900–2,800 cm⁻¹ corresponding to alkyl (-CH2) groups, confirming its polymer backbone stability (Chang et al., 2024). Notably, the presence of broad and merged peaks in the spectrum of the HA-PVA hydrogel suggests extensive hydrogen bonding between the –OH groups of both polymers, which is essential for forming a uniform and stable hydrogel matrix (Muangsri et al., 2022). The cross-linked HA-PVA hydrogel spectrum displayed notable changes broad hydroxyl (-OH) absorption at 3,400–3,300 cm⁻¹ and combined peaks for alkyl (-CH2) and amine (-NH) groups, indicating successful integration of HA and PVA into a hybrid network. These spectral modifications particularly the broadening and shift of the –OH band indicate a transition from physical mixtures to a chemically interacting network, validating the formation of a semi-interpenetrating polymer structure (D Agostino, 2012). Reduced peak intensities and shifts suggest chemical interactions between hydroxyl and carboxyl groups, forming a more stable, interconnected polymer structure. These structural changes improve mechanical strength and support the hydrogel’s suitability for microneedle applications. Overall, FT-IR analysis confirms that HA-PVA cross-linking modifies the chemical structure to form a stable hydrogel network, enhancing properties essential for wound healing, drug delivery, and skin regeneration. This insight guides optimization of HA-PVA formulations for advanced biomedical uses.

Figure 1. FT-IR spectra of cross-linked HA-PVA, pure HA and pure PVA.

Swelling rate test

The water absorption and swelling behavior of HA-PVA microneedles with varying HA concentrations (0%, 0.5%, 1%, 1.5%, and 2%) were investigated. The results showed that increasing the HA content significantly enhanced both water uptake and swelling capacity (P < 0.05, one-way ANOVA, Tukey’s post-hoc test), with microneedles containing 2% HA swelling to nearly twice the extent of those with 0.5% HA. As shown in Figure 2, this demonstrates a clear correlation between HA concentration and swelling performance. The swelling was most rapid during the initial three hours, particularly for samples with higher HA levels, where the 2% HA microneedles exhibited the greatest increase (P < 0.01 compared to 0.5% HA). This behavior is attributed to the hygroscopic nature of hyaluronic acid, a highly hydrophilic biopolymer capable of forming hydrogen bonds with water molecules (Bokatyi et al., 2024). As HA content increases, more hydroxyl and carboxyl functional groups become available in the polymer network, enhancing water-binding capacity (Mahmoudi et al., 2024). These functional groups not only attract water but also promote hydrogel network expansion through osmotic swelling pressure (Nalampang et al., 2007; Sionkowska et al., 2020). Consistent with previous studies, it has been reported that one of the key characteristics of hydrogels lies in their ability to absorb and retain water due to the presence of high-affinity hydrophilic functional groups, which supports the observed swelling behavior in HA-PVA microneedles. Such groups facilitate water uptake and contribute directly to the increased swelling ratio, especially in formulations with higher HA content (Liang et al., 2020; Kimi and Chong, 2025). After three hours, the swelling rate decreased as the system approached equilibrium microneedles with lower HA concentrations (0.5%) stabilized more quickly, while those with higher concentrations (2%) required more time. These findings highlight the important role of HA concentration in governing the swelling characteristics of hydrogels, which directly affects their suitability for applications such as wound healing and controlled drug delivery. Adjusting HA content allows for optimization of moisture retention and targeted release profiles (Moawad et al., 2025).

Figure 2. Percentage swelling of HA-PVA microneedles at different HA concentrations in DI water at 25°C. Data are expressed as mean ± SD (n = 3). Statistical analysis was performed using one-way ANOVA with Tukey’s post-hoc test; *P < 0.05, **P < 0.01.

Tensile test

Mechanical strength and durability tests were conducted on microneedles (MNs) composed of hyaluronic acid (HA) and polyvinyl alcohol (PVA) with varying HA concentrations (0.5%, 1%, 1.5%, and 2%) using a Universal Testing Machine (UTM). The results demonstrated that HA concentration significantly affects the structural integrity and durability of microneedles (P < 0.05, one-way ANOVA). MNs containing 0.5% HA exhibited the highest tensile stress of 7.1 ± 1.6 MPa and tensile strain of 248 ± 32%, which was significantly higher than that of 2% HA microneedles (2.5 ± 2.1 MPa, 203 ± 19%; P < 0.01). As shown in Figure 3, MNs with the highest HA concentration of 2% showed a marked decrease in durability, with tensile stress dropping to 2.5 ± 2.1 MPa and tensile strain to 203 ± 19%, reflecting a tendency to tear more quickly under tensile load. This mechanical weakening is primarily attributed to the increased hydrophilicity of the microneedle matrix at higher HA concentrations (Bashir et al., 2020). Hyaluronic acid, while enhancing swelling and moisture retention, disrupts the interpolymer hydrogen bonding and network entanglement within the PVA matrix. As HA content rises, the hydrogel structure becomes more hydrated and flexible but also more prone to mechanical failure due to reduced cohesive strength between polymer chains (Moussa et al., 2025). Additionally, the increased water content resulting from higher HA levels acts as a plasticizer (Kitsongsermthon et al., 2021), softening the material and decreasing its resistance to applied tensile forces. This softening effect compromises the mechanical stability required for skin penetration, increasing the risk of needle bending, breaking, or incomplete insertion. These findings underscore the critical role of HA concentration in determining the mechanical performance of microneedles. While higher HA content enhances swelling and water retention, it also significantly compromises structural integrity by weakening the intermolecular interactions within the hydrogel network. This trend is consistent with previous studies, which have similarly reported that hydrogel systems with elevated HA levels tend to exhibit increased softness and brittleness under mechanical stress (Lyu et al., 2023). Therefore, optimizing the HA-to-PVA ratio is essential to achieve a balance between adequate swelling behavior and mechanical robustness, two key factors that determine the effectiveness of microneedles in transdermal drug delivery applications.

Figure 3. Tensile strength of crosslinked HA-PVA microneedles at different HA concentrations. Data are expressed as mean ± SD (n = 3). Statistical analysis was performed using one-way ANOVA with Tukey’s post-hoc test; *P < 0.05, **P < 0.01.

Drug release study

Microneedles used in this study consist of tiny, pyramid-shaped projections arranged on a base for easy handling. These microneedles are fabricated from a hydrogel matrix composed of hyaluronic acid (HA) and polyvinyl alcohol (PVA), both known for their biocompatibility and water-soluble properties. Each needle features a sharp tip designed to effectively penetrate the stratum corneum, the outermost layer of skin. Upon contact with skin moisture, the microneedles gradually dissolve, enabling sustained release of the encapsulated drug (Lyu et al., 2023; Chudzińska et al., 2024). To assess skin penetration efficiency and drug release behavior, the microneedles were coated with crystal violet dye as a model drug and then applied to porcine skin (Kitsongsermthon et al., 2021). The initial physical characteristics of the microneedles are presented in Figure 4, clearly showing their uniform size, shape, and arrangement. These features confirm that the microneedles are well-structured and sharp enough for efficient skin insertion and subsequent drug delivery. Microscopic images of micropores on porcine skin, created by the HA-PVA dissolving microneedles, were analyzed to evaluate penetration efficiency and drug diffusion. As illustrated in Figure 5, observations at 0, 30, 60, 90, and 120 minutes post-application revealed a progressive increase in crystal violet intensity. This trend indicates gradual microneedle degradation and pore formation within the skin, which in turn enhances drug permeation into deeper skin layers. At lower concentrations of HA (0.5% and 1%), the microneedles tend to dissolve more quickly, resulting in rapid initial drug release (crystal violet) and more visible staining on the skin during the early time points. However, drug release tends to decrease over time as the microneedles fully dissolve shortly after application. In contrast, higher HA concentrations (1.5% and 2%) enhance the hydrogel matrix's ability to absorb water and swell, causing the microneedles to dissolve more gradually. This gradual dissolution creates additional voids in the matrix over time, enabling a sustained and deeper drug diffusion into the skin layers. Therefore, adjusting the HA concentration influences the drug release profile: lower concentrations are suitable for fast, initial drug delivery, while higher concentrations support sustained release and deeper skin penetration over an extended period. (Leelapornpisid et al., 2014; Chen et al., 2018; Kitsongsermthon et al., 2021).

Figure 4. HA-PVA microneedles on optical microscope.

Figure 5. Penetrating dissolved microneedles after being stained with crystal violet on the porcine skin for 30, 60, 90 and 120 min (a) HA0.5% (b) HA1% (c) HA1.5% (d) HA2%.

Antibacterial test

The antibacterial testing of HA-PVA microneedles at different HA concentrations showed a clear positive effect on inhibiting Escherichia coli and Staphylococcus aureus as shown in Figure 6. Pure PVA microneedles (control) had minimal inhibition zones (~2 mm for E. coli, ~3 mm for S. aureus). Adding 0.5% HA increased the zones to ~36 mm (E. coli) and ~41 mm (S. aureus), showing moderate antibacterial activity. At 1% HA, inhibition zones further improved to 58 mm (E. coli) and 55 mm (S. aureus), and at 1.5% HA, to 66 mm and 61 mm respectively, indicating enhanced efficacy. The highest antibacterial activity was observed at 2% HA, with inhibition zones of 91 mm (E. coli) and 87 mm (S. aureus). These results demonstrate that increasing HA concentration significantly enhances antibacterial performance (Fahmy et al., 2015). The gradual and substantial increase in inhibition zone size from 0.5% to 2% HA suggests that HA plays a dose-dependent role in disrupting bacterial growth. This is likely due to HA’s ability to interfere with bacterial adhesion and biofilm formation, particularly through saturation of bacterial hyaluronidase, an enzyme many pathogens use to penetrate host tissues (Ibberson et al., 2016). When HA is present in sufficient quantities, it may bind and inhibit these enzymes, preventing tissue invasion and colonization (Zamboni et al., 2022). Therefore, the results not only validate HA's antibacterial potential but also highlight the importance of optimizing its concentration in HA-PVA microneedle systems. An appropriate HA loading not only enhances antimicrobial activity but also maintains biocompatibility and structural integrity of the microneedles, making it crucial for clinical translation in wound healing, infection prevention, and transdermal drug delivery applications.

Figure 6. The antibacterial test results of Pure PVA, HA0.5%, HA1%, HA1.5% and HA2% (A) E. coli (B) S. aureus (C) Clear zone (mm).

DISCUSSION

FT-IR analysis confirmed the successful formation of a cross-linked HA-PVA hydrogel network, with the broadening and shifting of –OH peaks indicating extensive hydrogen bonding and the establishment of a semi-interpenetrating polymer structure. Similar spectral changes have been reported in previous HA-PVA hydrogel studies, where intermolecular hydrogen bonding was a key factor in network stability (D’Agostino, 2012; Muangsri et al., 2022), supporting the reliability of the present findings.

Swelling tests demonstrated that increasing HA content enhanced water absorption and hydrogel expansion, particularly during the initial hours. This agrees with earlier reports highlighting the hygroscopic nature of HA and its numerous hydroxyl and carboxyl groups that readily interact with water molecules (Bokatyi et al., 2024; Mahmoudi et al., 2024). Our results further indicate that HA concentration strongly influences water uptake kinetics, consistent with patterns described for HA-based wound dressings that promote rapid hydration and tissue compatibility.

Mechanical testing revealed that lower HA concentrations (0.5%) provided higher tensile strength and strain, whereas higher HA levels (2%) decreased mechanical stability, likely due to increased hydration and plasticizing effects. This trend is in line with the observations of Bashir et al. (2020) and Moussa et al. (2025), who noted that excessive HA content compromises mechanical robustness of hydrogels, suggesting the necessity of balancing polymer ratios to ensure structural integrity for microneedle applications. Nevertheless, the material containing 2% HA was selected for further detailed study due to its superior swelling and sustained drug release capabilities, which are critical for prolonged therapeutic efficacy in wound healing. Although this formulation exhibits reduced mechanical strength, it still meets the minimum mechanical requirements for skin penetration when processed using optimized fabrication parameters. This trade-off reflects a strategic choice prioritizing functional drug delivery and hydration properties while maintaining adequate structural performance for microneedle application.

Drug absorption and release studies showed that HA concentration modulated release kinetics: lower HA levels promoted rapid release, while higher concentrations enabled sustained diffusion. These results correspond well with previous reports on HA-containing delivery systems, where high HA content prolonged drug retention and controlled release through denser hydrogel networks (Kitsongsermthon et al., 2021; Chudzińska et al., 2024). Thus, our findings confirm the tunability of HA-PVA hydrogels for tailoring drug delivery rates.

Antibacterial assays demonstrated dose-dependent efficacy, with higher HA levels significantly inhibiting E. coli and S. aureus. This is consistent with earlier studies attributing HA’s antibacterial activity to interference with bacterial adhesion, cell wall integrity, and hyaluronidase activity (Fahmy et al., 2015; Ibberson et al., 2016). Importantly, the antibacterial effects observed here align with reports showing HA’s potential as both a barrier and an active antibacterial component in wound healing formulations.

Overall, these results highlight the pivotal role of HA concentration in balancing mechanical strength, swelling behavior, drug release, and antibacterial properties. By directly comparing our findings with previous literature, it becomes clear that HA-PVA microneedles not only reproduce known benefits of HA-based hydrogels but also extend their application toward wound healing and transdermal drug delivery. This comparative analysis underscores the translational potential of the developed system while identifying optimal HA concentrations that achieve multifunctionality.

CONCLUSION

In summary, this study highlights the potential of hyaluronic acid (HA) and polyvinyl alcohol (PVA)-based microneedles (MNs) for advanced wound healing and drug delivery applications. By varying the HA concentration, key insights were gained into their structural, mechanical, and biomedical performance. FT-IR analysis confirmed effective cross-linking between HA and PVA, forming stable hydrogel networks that maintain HA's hydrophilic nature while enhancing mechanical strength. Tensile tests revealed that MNs with lower HA concentrations (0.5% and 1%) possessed optimal mechanical properties, with superior strength and flexibility for skin penetration. In contrast, higher concentrations (1.5% and 2%) led to increased water absorption but reduced durability, likely due to polymer matrix softening. Swelling behavior showed a direct correlation with HA content, higher concentrations absorbed water rapidly and remained hydrated longer supporting their use in maintaining a moist wound environment. Antibacterial assays demonstrated that higher HA concentrations significantly enhanced inhibition against E. coli and S. aureus, with the strongest effects observed at 2% HA, indicating strong potential for infection prevention. Drug permeation studies using porcine skin and crystal violet as a model compound showed that MNs with higher HA levels allowed deeper and more uniform diffusion. This can be attributed to enhanced hydrogel swelling and gradual microneedle degradation, promoting sustained and controlled drug release. Collectively, the findings underscore the importance of optimizing HA concentration to balance mechanical strength, swelling behavior, antibacterial efficacy, and drug release performance. HA-PVA microneedles represent a promising platform for localized therapeutic delivery and next-generation medical applications aimed at improving patient outcomes.

ACKNOWLEDGEMENTS

This research work was supported by the Research Fund of the Faculty of Engineering, Khon Kaen University under the Research Scholarship for M.Eng. Students project under Contract Nos.M-Eng.-CHE.-007/2568.

AUTHOR CONTRIBUTIONS

Naritsara Suwatsrisakun: Conceptualization (Lead), Methodology (Lead), Writing-Original Draft (Lead), Investigation (Equal), Project Administration (Equal), Data Analyze (Lead); Chanyanuch Prungruan: Methodology (Equal), Writing and Editing (Equal), Investigation (Supportive); Duangkanok Tanangteerapong: Resource (Equal), Supervision (Lead), Critical Guidance (Lead), Reviewing and Editing (Lead), Project Administration (Lead).

CONFLICT OF INTEREST

The authors declare that they hold no competing interests.

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