Fiber-Reinforced Silk Microneedle Patches for Improved Tissue Adhesion in Treating Diabetic Wound Infections

Yixin Wang, Pengpeng Guan, Ruiyi Tan, Zhenghui Shi, Qing Li, Bitao Lu, Enling Hu, Weiwei Ding, Wenyi Wang, Bowen Cheng, Guangqian Lan, Fei Lu

Advanced Fiber Materials ›› 2024, Vol. 6 ›› Issue (5) : 1596-1615. DOI: 10.1007/s42765-024-00439-z
Research Article

Fiber-Reinforced Silk Microneedle Patches for Improved Tissue Adhesion in Treating Diabetic Wound Infections

Author information +
History +

Abstract

Microneedles (MNs) with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery. However, existing hydrogel MNs exhibit poor mechanical properties after swelling and require complex preparation procedures, impeding their practical application. Hence, we engineered chitosan fiber-reinforced silk fibroin MN patches containing epigallocatechin gallate (SCEMN). A formic acid–calcium chloride system was introduced to fabricate hydrogel MNs with excellent inherent adhesion, and the incorporation of chitosan fiber as a reinforcing material enhanced mechanical strength and viscosity, thereby increasing the physical interlocking with tissue and the ability to maintain shape. The SCEMN with a lower insertion force firmly adhered to porcine skin, with a maximum detachment force of 11.98 N/cm2. Additionally, SCEMN has excellent antioxidant and antibacterial properties, facilitates macrophage polarization from M1 to M2, and demonstrates superior performance in vivo for diabetic wound repair compared with the commercial product Tegaderm™. This study represents the first trial of fiber-reinforced hydrogel MNs for robust tissue adhesion. Our findings underscore the significance of this innovative approach for advancing MN technology to enhance tissue adhesion and accelerate wound healing.

Keywords

Fibrous reinforcement / Double-sided microneedle patch / Swellable hydrogel / Tissue adhesion

Cite this article

Download citation ▾
Yixin Wang, Pengpeng Guan, Ruiyi Tan, Zhenghui Shi, Qing Li, Bitao Lu, Enling Hu, Weiwei Ding, Wenyi Wang, Bowen Cheng, Guangqian Lan, Fei Lu. Fiber-Reinforced Silk Microneedle Patches for Improved Tissue Adhesion in Treating Diabetic Wound Infections. Advanced Fiber Materials, 2024, 6(5): 1596‒1615 https://doi.org/10.1007/s42765-024-00439-z

References

[1]
Loh JM, Lim YJL, Tay JT, Cheng HM, Tey HL, Liang K. Design and fabrication of customizable microneedles enabled by 3d printing for biomedical applications. Bioact Mater, 2024, 32: 222
[2]
Zhang XP, He YT, Li WX, Chen BZ, Zhang CY, Cui Y, Guo XD. An update on biomaterials as microneedle matrixes for biomedical applications. J Mater Chem B, 2022, 10: 6059,
CrossRef Google scholar
[3]
Li J, Ge R, Lin K, Wang J, He Y, Lu H, Dong H. Advances in the application of microneedles in the treatment of local organ diseases. Small, 2024, 20: 2306222,
CrossRef Google scholar
[4]
Ma W, Zhang X, Liu Y, Fan L, Gan J, Liu W, Zhao Y, Sun L. Polydopamine decorated microneedles with fe-msc-derived nanovesicles encapsulation for wound healing. Adv Sci, 2022, 9,
CrossRef Google scholar
[5]
Qian L, Jin F, Wei Z, Li T, Sun Z, Lai C, Ma J, Xiong R, Ma X, Wang F, Sun F, Zheng W, Dong W, Sun K, Wang T, Feng Z-Q. Wearable, self-powered, drug-loaded electronic microneedles for accelerated tissue repair of inflammatory skin disorders. Adv Funct Mater, 2023, 33: 2209407,
CrossRef Google scholar
[6]
Kang S, Song JE. Sugar-triggered burst drug releasing poly-lactic acid (pla) microneedles and its fabrication based on solvent-casting approach. Pharmaceutics, 2022, 14: 1758,
CrossRef Google scholar
[7]
GhavamiNejad A, Li J, Lu B, Zhou L, Lam L, Giacca A, Wu XY. Glucose-responsive composite microneedle patch for hypoglycemia-triggered delivery of native glucagon. Adv Mater, 2019, 31: 1901051,
CrossRef Google scholar
[8]
Fan L, Zhang X, Nie M, Xu Y, Wang Y, Shang L, Zhao Y, Zhao Y. Photothermal responsive microspheres-triggered separable microneedles for versatile drug delivery. Adv Funct Mater, 2022, 32: 2110746,
CrossRef Google scholar
[9]
Choi SO, Kim YC, Lee JW, Park JH, Prausnitz MR, Allen MG. Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array. Small, 2012, 8: 1081,
CrossRef Google scholar
[10]
Li J, Lu H, Wang Y, Yang S, Zhang Y, Wei W, Qiao Y, Dai W, Ge R, Dong H. Interstitial fluid biomarkers’ minimally invasive monitoring using microneedle sensor arrays. Anal Chem, 2022, 94: 968,
CrossRef Google scholar
[11]
Zhang X, Wang Y, Chi J, Zhao Y. Smart microneedles for therapy and diagnosis. Research, 2020,
CrossRef Google scholar
[12]
Anjani QK, Sabri AHB, Utomo E, Domínguez-Robles J, Donnelly RF. Elucidating the impact of surfactants on the performance of dissolving microneedle array patches. Mol Pharm, 2022, 19: 1191,
CrossRef Google scholar
[13]
Zhi-Chen B, Ting-He Y, Qiang-Zhao Z, Hao-Feng Y, Liang L, Peng J, Yu-Yang C, Uyama H, Shahbazi M-A, Dong-Guo X. Strategies to develop polymeric microneedles for controlled drug release. Adv Drug Del Rev., 2023, 203,
CrossRef Google scholar
[14]
Liu X, Liu J, Wang J, Wang T, Jiang Y, Hu J, Liu Z, Chen X, Yu J. Bioinspired, microstructured silk fibroin adhesives for flexible skin sensors. ACS Appl Mater Interfaces, 2020, 12: 5601,
CrossRef Google scholar
[15]
Jeon EY, Lee J, Kim BJ, Joo KI, Kim KH, Lim G, Cha HJ. Bio-inspired swellable hydrogel-forming double-layered adhesive microneedle protein patch for regenerative internal/external surgical closure. Biomaterials, 2019, 222,
CrossRef Google scholar
[16]
Zhang X, Chen G, Cai L, Wang Y, Sun L, Zhao Y. Bioinspired pagoda-like microneedle patches with strong fixation and hemostasis capabilities. Chem Eng J, 2021, 414,
CrossRef Google scholar
[17]
Lyu S, Dong Z, Xu X, Bei H-P, Yuen H-Y, James Cheung C-W, Wong M-S, He Y, Zhao X. Going below and beyond the surface: microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration. Bioact Mater, 2023, 27: 303
[18]
Wu Y, Tang Z, Ma S, Du L. The promising application of hydrogel microneedles in medical application. J Pharm Pharmacol, 2023, 75: 1011,
CrossRef Google scholar
[19]
Chen G, Matsuhisa N, Liu Z, Qi D, Cai P, Jiang Y, Wan C, Cui Y, Leow WR, Liu Z, Gong S, Zhang K-Q, Cheng Y, Chen X. Plasticizing silk protein for on-skin stretchable electrodes. Adv Mater, 2018, 30: 1800129,
CrossRef Google scholar
[20]
Ni B, Kaplan DL, Buehler MJ. Generative design of de novo proteins based on secondary-structure constraints using an attention-based diffusion model. Chem, 1828, 2023: 9
[21]
Sahoo JK, Hasturk O, Falcucci T, Kaplan DL. Silk chemistry and biomedical material designs. Nat Rev Chem, 2023, 7: 302,
CrossRef Google scholar
[22]
Xiong L, Wang H, Wang J, Luo J, Xie R, Lu F, Lan G, Ning L-J, Yin R, Wang W, Hu E. Facilely prepared thirsty granules arouse tough wet adhesion on overmoist wounds for hemostasis and tissue repair. ACS Appl Mater Interfaces, 2023, 15: 49035,
CrossRef Google scholar
[23]
Seo J-W, Kim H, Kim K, Choi SQ, Lee HJ. Calcium-modified silk as a biocompatible and strong adhesive for epidermal electronics. Adv Funct Mater, 2018, 28,
CrossRef Google scholar
[24]
Liu S, Zhang Q, Yu J, Shao N, Lu H, Guo J, Qiu X, Zhou D, Huang Y. Absorbable thioether grafted hyaluronic acid nanofibrous hydrogel for synergistic modulation of inflammation microenvironment to accelerate chronic diabetic wound healing. Adv Healthc Mater, 2020, 9,
CrossRef Google scholar
[25]
Bao Z, Xian C, Yuan Q, Liu G, Wu J. Natural polymer-based hydrogels with enhanced mechanical performances: preparation, structure, and property. Adv Healthcare Mater, 2019, 8: 1900670,
CrossRef Google scholar
[26]
Maiti S, Islam MR, Uddin MA, Afroj S, Eichhorn SJ, Karim N. Sustainable fiber-reinforced composites: a review. Adv Sustain Syst, 2022, 6: 2200258,
CrossRef Google scholar
[27]
Wang M, Gu J, Hao Y, Qin X, Yu Y, Zhang H. Adhesive, sustained-release, antibacterial, cytocompatible hydrogel-based nanofiber membrane assembled from polysaccharide hydrogels and functionalized nanofibers. Cellulose, 2023, 30: 323,
CrossRef Google scholar
[28]
Peng R, Ba F, Li J, Cao J, Zhang R, Liu W-Q, Ren J, Liu Y, Li J, Ling S. Embedding living cells with a mechanically reinforced and functionally programmable hydrogel fiber platform. Adv Mater, 2023, 35: 2305583,
CrossRef Google scholar
[29]
Wang Y, Xie R, Li Q, Dai F, Lan G, Shang S, Lu F. A self-adapting hydrogel based on chitosan/oxidized konjac glucomannan/agnps for repairing irregular wounds. Biomater Sci, 1910, 2020: 8
[30]
Kong XQ, Zhou P, Wu CW. Numerical simulation of microneedles’ insertion into skin. Comput Methods Biomech Biomed Eng, 2011, 14: 827,
CrossRef Google scholar
[31]
Yadav PR, Dobson LJ, Pattanayek SK, Das DB. Swellable microneedles based transdermal drug delivery: mathematical model development and numerical experiments. Chem Eng Sci, 2022, 247,
CrossRef Google scholar
[32]
Li Y, Zheng H, Liang Y, Xuan M, Liu G, Xie H. Hyaluronic acid-methacrylic anhydride/polyhexamethylene biguanide hybrid hydrogel with antibacterial and proangiogenic functions for diabetic wound repair. Chin Chem Lett, 2022, 33: 5030,
CrossRef Google scholar
[33]
Chiu TM, Hsu PC, Khan MY, Lin CJ, Lee CH, Hsu TC, Chen MH. A perspective on imiquimod microneedles for treating warts. Pharmaceutics, 2021, 13: 607,
CrossRef Google scholar
[34]
Yin Z, Kuang D, Wang S, Zheng Z, Yadavalli VK, Lu S. Swellable silk fibroin microneedles for transdermal drug delivery. Int J Biol Macromol, 2018, 106: 48,
CrossRef Google scholar
[35]
Zhou X, Luo Z, Baidya A, Kim H-J, Wang C, Jiang X, Qu M, Zhu J, Ren L, Vajhadin F, Tebon P, Zhang N, Xue Y, Feng Y, Xue C, Chen Y, Lee K, Lee J, Zhang S, Xu C, Ashammakhi N, Ahadian S, Dokmeci MR, Gu Z, Sun W, Khademhosseini A. Biodegradable β-cyclodextrin conjugated gelatin methacryloyl microneedle for delivery of water-insoluble drug. Adv Healthc Mater., 2020, 9,
CrossRef Google scholar
[36]
Hu P, Chiarini A. Exosomes of adult human fibroblasts cultured on 3d silk fibroin nonwovens intensely stimulate neoangiogenesis. Burns & trauma, 2021, 9,
CrossRef Google scholar
[37]
Liu L, Hu E, Qiu H, Xu Q, Yu K, Xie R, Lu F, Wang Q, Lu B, Li Q, Lan G. Dual modes reinforced silk adhesives for tissue repair: Integration of textiles and inorganic particles in silk gel for enhanced mechanical and adhesive strength. Int J Biol Macromol, 2023, 242,
CrossRef Google scholar
[38]
Zhou G, Shao Z, Knight DP, Yan J, Chen X. Silk fibers extruded artificially from aqueous solutions of regenerated bombyx mori silk fibroin are tougher than their natural counterparts. Adv Mater, 2009, 21: 366,
CrossRef Google scholar
[39]
Kong D, Quan C, Xi Q, Han R, Koseki S, Li P, Du Q, Yang Y, Forghani F, Wang J. Study on the quality and myofibrillar protein structure of chicken breasts during thawing of ultrasound-assisted slightly acidic electrolyzed water (saew). Ultrason Sonochem, 2022, 88,
CrossRef Google scholar
[40]
Yang C, Shang S, Shou D, Ran L, Lan G, Hu E. Transforming natural silk nonwovens into robust bioadhesives for in vivo tissue amendment. J Clean Prod, 2021, 314,
CrossRef Google scholar
[41]
Martel A, Burghammer M, Davies RJ, Di Cola E, Vendrely C, Riekel C. Silk fiber assembly studied by synchrotron radiation saxs/waxs and raman spectroscopy. J Am Chem Soc, 2008, 130: 17070,
CrossRef Google scholar
[42]
Hernández B, Coïc Y-M, Pflüger F, Kruglik SG, Ghomi M. All characteristic raman markers of tyrosine and tyrosinate originate from phenol ring fundamental vibrations. J Raman Spectrosc, 2016, 47: 210,
CrossRef Google scholar
[43]
Zeng J, Ren X, Zhu S, Gao Y. Fabrication and characterization of an economical active packaging film based on chitosan incorporated with pomegranate peel. Int J Biol Macromol, 2021, 192: 1160,
CrossRef Google scholar
[44]
Xu C, Guan S, Wang B, Wang S, Wang Y, Sun C, Ma X, Liu T. Synthesis of protocatechuic acid grafted chitosan copolymer: Structure characterization and in vitro neuroprotective potential. Int J Biol Macromol, 2018, 109: 1,
CrossRef Google scholar
[45]
Shu W, Heimark H, Bertollo N, Tobin DJ, O’Cearbhaill ED, Annaidh AN. Insights into the mechanics of solid conical microneedle array insertion into skin using the finite element method. Acta Biomater, 2021, 135: 403,
CrossRef Google scholar
[46]
Perez Cuevas MB, Kodani M, Choi Y, Joyce J, O’Connor SM, Kamili S, Prausnitz MR. Hepatitis b vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques. Bioeng Transl Med, 2018, 3: 186,
CrossRef Google scholar
[47]
Yuk H, Varela CE, Nabzdyk CS, Mao X, Padera RF, Roche ET, Zhao X. Dry double-sided tape for adhesion of wet tissues and devices. Nature, 2019, 575: 169,
CrossRef Google scholar
[48]
Yang SY, O’Cearbhaill ED, Sisk GC, Park KM, Cho WK, Villiger M, Bouma BE, Pomahac B, Karp JM. A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue. Nat Commun, 2013, 4: 1702,
CrossRef Google scholar
[49]
Sosson F, Chateauminois A, Creton C. Investigation of shear failure mechanisms of pressure-sensitive adhesives. J Polym Sci, Part B: Polym Phys, 2005, 43: 3316,
CrossRef Google scholar
[50]
Mao X, Yuk H, Zhao X. Hydration and swelling of dry polymers for wet adhesion. J Mech Phys Solids, 2020, 137,
CrossRef Google scholar
[51]
Tao X, Jiang F, Cheng K, Qi Z, Yadavalli VK, Lu S. Synthesis of ph and glucose responsive silk fibroin hydrogels. Int J Mol Sci, 2021, 22: 7107,
CrossRef Google scholar
[52]
Yang Y, Zhao X, Yu J, Chen X, Wang R, Zhang M, Zhang Q, Zhang Y, Wang S, Cheng Y. Bioactive skin-mimicking hydrogel band-aids for diabetic wound healing and infectious skin incision treatment. Bioact Mater, 2021, 6: 3962
[53]
Wei L, Tan J, Li L, Wang H, Liu S, Chen J, Weng Y, Liu T. Chitosan/alginate hydrogel dressing loaded fgf/ve-cadherin to accelerate full-thickness skin regeneration and more normal skin repairs. Int J Mol Sci, 2022, 23: 1249,
CrossRef Google scholar
[54]
Zhao X, Pei D, Yang Y, Xu K, Yu J, Zhang Y, Zhang Q, He G, Zhang Y, Li A, Cheng Y, Chen X. Green tea derivative driven smart hydrogels with desired functions for chronic diabetic wound treatment. Adv Funct Mater, 2021, 31: 2009442,
CrossRef Google scholar
[55]
Liu G, Zhou Y, Xu Z, Bao Z, Zheng L, Wu J. Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing. Chin Chem Lett, 2023, 34,
CrossRef Google scholar
[56]
Wang D, Liu J, Qiu S, Wang J, Song G, Chu B, Li L, Xiao G, Gong J, Zheng F. Ultrasonic degradation kinetics and isomerization of 3- and 4-o-caffeoylquinic acid at various ph: the protective effects of ascorbic acid and epigallocatechin gallate on their stability. Ultrason Sonochem, 2021, 80,
CrossRef Google scholar
[57]
Hong Y, Zhou F, Hua Y, Zhang X, Ni C, Pan D, Zhang Y, Jiang D, Yang L, Lin Q, Zou Y, Yu D, Arnot DE, Zou X, Zhu L, Zhang S, Ouyang H. A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds. Nat Commun, 2019, 10: 2060,
CrossRef Google scholar
[58]
Johnson CT, Wroe JA, Agarwal R, Martin KE, Guldberg RE, Donlan RM, Westblade LF, García AJ. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc Natl Acad Sci U S A, 2018, 115: E4960,
CrossRef Google scholar
[59]
Yuan Y, Fan D, Shen S, Ma X. An m2 macrophage-polarized anti-inflammatory hydrogel combined with mild heat stimulation for regulating chronic inflammation and impaired angiogenesis of diabetic wounds. Chem Eng J, 2022, 433,
CrossRef Google scholar
[60]
Wu Y, Yao Y, Zhang J, Gui H, Liu J, Liu J. Tumor-targeted injectable double-network hydrogel for prevention of breast cancer recurrence and wound infection via synergistic photothermal and brachytherapy. Adv Sci, 2022, 9: 2200681,
CrossRef Google scholar
[61]
Deng S, Huang Y, Hu E, Ning L-J, Xie R, Yu K, Lu F, Lan G, Lu B. Chitosan/silk fibroin nanofibers-based hierarchical sponges accelerate infected diabetic wound healing via a hclo self-producing cascade catalytic reaction. Carbohydr Polym, 2023, 321,
CrossRef Google scholar
[62]
Correction to Functional extracellular matrix hydrogel modified with msc-derived small extracellular vesicles for chronic wound healing. Cell Prolif 2023, 56, e13553.
[63]
Guo W, Qiu W, Ao X, Li W, He X, Ao L, Hu X, Li Z, Zhu M, Luo D, Xing W, Xu X. Low-concentration dmso accelerates skin wound healing by akt/mtor-mediated cell proliferation and migration in diabetic mice. Br J Pharmacol, 2020, 177: 3327,
CrossRef Google scholar

Accesses

Citations

Detail

Sections
Recommended

/