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. 2023 Aug 29:22:100782.
doi: 10.1016/j.mtbio.2023.100782. eCollection 2023 Oct.

Multifunctional polysaccharide composited microneedle for oral ulcers healing

Yiyu Zeng  1 , Yijun Gao  1 , Liming He  2 , Wenhui Ge  1 , Junhui Liu  3 , Yi Yu  1 , Xiaoyan Xie  1
Affiliations

Multifunctional polysaccharide composited microneedle for oral ulcers healing

Yiyu Zeng et al. Mater Today Bio. .

Abstract

Oral ulcers have periodicity and recurrence, and the etiology and causative mechanisms remain unclear; therefore, it is difficult to treat oral ulcers effectively. Current clinical treatment methods mainly include pain relief and administration of anti-inflammatories to prevent secondary infections and a prolonged recurrence cycle. However, these traditional treatment methods are administered independently and are susceptible to muscle movements and constant salivary secretion in the mouth, resulting in ineffective drug functioning. Therefore, development of a novel treatment to reduce wound infection and accelerate wound healing for oral ulcers is required for effective treatment. Herein, we report a multifunctional polysaccharide composite microneedle patch based on hyaluronic acid (HA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) loaded with dexamethasone (DXMS) and basic fibroblast growth factor (bFGF) for oral ulcer healing. DXMS and bFGF encapsulated the HA tip portion of the microneedle patch, endowing the microneedle patches with anti-inflammatory and angiogenic properties. HACC was applied to the back of the microneedle patch, adding antibacterial properties. The experimental results indicated that the prepared dressings exhibited good antibacterial activity and effectively promoted cell migration growth and angiogenesis. More importantly, animal experiments have shown that multifunctional microneedle patches can effectively promote oral ulcer healing. Thus, these novel multifunctional polysaccharide composite microneedle patches have great potential for oral ulcers treatment.

Keywords: Hyaluronic acid; Microneedle; Oral ulcers; Polysaccharide; Wound healing.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Schematic presentation of the application of multifunctional HA/HACC composited microneedles patches for promoting oral ulcers healing. HACC, hydroxypropyl trimethyl ammonium chloride chitosan; HA, hyaluronic acid; DXMS, dexamethasone; bFGF, basic fibroblast growth factor; E. coli, Escherichia coli; S. aureus, Staphylococcus aureus; C. albicans, Candida albicans; WBC, white blood cell; EC, endothelial cell.
Fig. 2
Fig. 2
Characterization of HA/HACC MN patches. (A–C) Images of intact and magnified MN patches based on optical microscopy. (D–F) SEM images showing surface microstructures. (G–I) Fluorescence images of the tip of the HA/HACC MN patches loaded with Lumisphere. Scale bars respectively are (A) 5 mm, (B, D, G) 500 μm, (C, E, H) 200 μm, (F) 10 μm and (I) 100 μm.
Fig. 3
Fig. 3
Physical properties of MN patches. (A) Mechanical strength of the MN patch with different concentrations of HA. (B, C) The penetration assay in rat oral mucosa. (D) Mechanical strength of different MN patches. (E) The red fluorescent RhoB-loaded MN patches is tightly attached to the mucosal surface. (F) HE staining images after MN patch puncture. (G) The MN patch can be completely dissolved within 2 min. The scar bar are (B, C) 5 mm and (E, F, G) 200 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 4
Fig. 4
Investigation of biocompatibility ability and cell viability of MN patches. (A) Live/dead fluorescent images of HOrF. (B) Live/dead fluorescent images of HUVEC. (C) Quantitative Statistics of HOrF live cells. (D) Quantitative Statistics of HUVEC live cells. (E) CCK8 cell viability assay of HOrF. (F) CCK8 cell viability assay of HUVEC. The scale bars are 100 μm *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Fig. 5
Fig. 5
Evaluation of migration and angiogenesis ability in vitro. (A) Representative images of the cell migration assay of HOrF after different treatments. (B) Representative images of the cell migration assay of HUVEC after different treatments. (C) Fluorescence images of calcein-AM labeling HUVEC tube formation after various treatments. (D) Quantitative analysis of cell migration of HOrF. (E) Quantitative analysis of cell migration of HUVEC. (F) Analysis of tube length results. (G) Analysis of branching tubes. Scale bars are 100 μm *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Fig. 6
Fig. 6
Investigation of the antibacterial ability of MN patch. (A, C) Fluorescence imaging and live bacteria rate of E. coli, S. aureus, S. mutans and C. albicans. (B, D) Plate coating results and colony counting of E. coli, S. aureus, S. mutans and C. albicans. The scale are (A) 100 μm and (B) 1 cm *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Fig. 7
Fig. 7
Healing of oral ulcers in rats after treatment. (A) Image of rats oral ulcers on Day 0, Day 1 and Day 6 of treatment. (B) HE staining images of oral ulcers tissue on Day 6. (C) Percentage of oral ulcer repaired on Day 6. (D) Oral mucosal epithelial integrity in rats on Day 6 of treatment. Scale bars are (A) 250 μm, and (B) 100 μm respectively. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Fig. 8
Fig. 8
Characterization of collagen deposition and proinflammatory factors. (A–C) Staining of collagen, TNF-α and IL-6. (D–F) Quantitative analysis of collagen deposition, TNF-α and IL-6 in different groups after treatment. The scale bars are (A) 100 μm and (B, C) 250 μm *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Fig. 9
Fig. 9
Characterization of neovascularization and macrophage polarization. (A) The fluorescent images of the immunostaining of α-SMA (green) and CD31 (red). (B) The fluorescent images of the immunostaining of CD86 (yellow) and CD206 (green). (C) The analysis of vessel density. (D) The analysis of M1/M2 macrophages ratio. The scale bars are (A) 250 μm and (B) 100 μm *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
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