Additional file 1 of Multifunctional fish gelatin hydrogel inverse opal films for wound healing

Additional file 1: Figure S1. (a) pH-driven deprotonation equilibria of PAA polymers. (b) The change of the volume and structure color of the IOF under pH-stimulus. (c) The red shift of the reflection peak during the pH increasing process. Figure S2. Optical images of the pH-responsive structural color change of the IOFs fabricated by templates with different nanoparticle sizes. Figure S3. The photographs of pH indicator paper and IOF put onto (a) normal skin and (b) infected wounds of SD rats. (c) the reference for pH values in the range of 1–14. The scale bars are 5 mm. Figure S4. Photographs of E. coli and S. aureus colonies treated with PBS, and IOF loaded with 4% CS. Scale bars are 2 cm. Figure S5. (a) The standard curve of FITC-BSA in the PBS buffer solution, R2 > 0.999. (b) Cumulative release curve of FITC-BSA in IOF loaded with 4% CS. Figure S6. Live staining of NIH-3T3 cells on (a) glass dish, (b) IOF and (c) IOF loaded with 4% CS and VEGF. (d) The statistical graph of cell viability. Scale bars are 100 μm. Figure S7. Hemolysis tests of IOF and IOF + CS + VEGF. Figure S8. (a) Representative photographs of the wound closure process treated with commercial dressing (CD), and IOF + CS + VEGF. (b) The statistical graph of the wound closure situation (n = 4). Figure S9. In vivo antibacterial test of (a) control group and IOF + CS + VEGF group. Scale bars are 2 cm. Figure S10. (a) Immunostaining of PCNA of granulation tissues in different groups. (c) Immunostaining of E-cadherin of granulation tissues in different groups. Scare bars are 50 μm. Figure S11. Double immunofluorescence staining of neovascularization, CD31(+) structures (red) were surrounded by α‐smooth muscle actin positive cells (green) in different groups: (a) Control, (b) IOF, (c) IOF + CS + VEGF. Scale bars are 50 μm. (d) Statistical analysis of vessel density in different groups after 9 days of wound repair. NS not significant, 0.01 < *p < 0.05, **p < 0.01 (n = 4). Figure S12. Photographs of the skin wounds treated with (a) PBS solution (control), (b) IOF, (c) the IOF loaded with both CS and VEGF. Scale bar is 5 mm

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs