Fig. 1. Schematic illustration of LEB@Cyan for sustained oxygenation and robust photobiomodulation.

Fig. 2. Characterization of cyanobacterial oxygenation under red-light irradiation. (a) The digital photograph of a homemade optical device to investigate cyanobacterial photosynthetic oxygenation with adjustable wavelengths and power densities. (b) Schematic illustration of the photosynthetic oxygenation of the cyanobacteria. (c) The dissolved oxygen concentration of the solution containing cyanobacteria (108cells/mL) irradiated with red light with different wavelengths (620, 640, 660, and 680 nm) and varied power densities (0, 2, 4, 6, 8, and 10mW/cm2). (d) The dissolved oxygen concentration of the solution containing cyanobacterial cells at indicated concentrations under red-light irradiation (660 nm, 2mW/cm2). (e) The dissolved oxygen concentration of the solution containing cyanobacteria (108cells/mL) with red-light irradiation (660 nm, 2mW/cm2) or dark treatment for four on-off cycles (15-min light and 15-min dark).

Fig. 3. Evaluation of in vitro photobiomodulation effects enabled by cyanobacterial cells under red light. (a) Schematic illustration of the in vitro experiments of photobiomodulation on HaCaT, HUVEC, and HSF cell lines. (b)–(g) The HIF-1α immunofluorescence images and the quantitative fluorescence analysis of HaCaT (b) and (c), HUVEC (d) and (e), and HSF (f) and (g) from different groups. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. n.s., not significant, *P<0.05 and ***P<0.001. (h) Schematic illustration of the Transwell setup for the evaluation experiments of in vitro photobiomodulation on HaCaT, HUVEC, and HSF cell lines. (i) and (j) Representative images and quantification of HaCaT migration from different groups. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. n.s., not significant, *P<0.05, **P<0.01, and ***P<0.001. (k) and (i) Representative images and quantification of tube formation of HUVEC from different groups. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. **P<0.01 and ***P<0.001. (m) and (n) Representative images and quantification of HSF cell proliferation from different groups. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. *P<0.05 and **P<0.01. (o)–(q) Relative intracellular ATP concentrations of HaCaT, HUVEC, and HSF cell lines with indicated treatments. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. **P<0.01 and ***P<0.001.

Fig. 4. Fabrication and characterization of LEB@Cyan. (a) The digital photograph of lightened LEB under ambient light (upper panel) and in the dark (lower panel). (b) The digital photograph of the forearm of a human wearing the lightened LEB under ambient light (upper panel) and in the dark (lower panel). (c) The infrared thermographic images of the forearm of a human with or without wearing the LEB. (d) Representative photographs of the LEB and LEB@Cyan. (e) The SEM images of the LEB and LEB@Cyan.

Fig. 5. Therapeutics of LEB@Cyan for diabetic wound healing in rats. (a) Schematic illustration of the in vivo treatment schedule of diabetic wound healing experiment. (b) The digital photographs of the rat dressed with lightened LEB@Cyan under ambient light and in the dark. (c) and (d) Representative images and quantification of the wounds of rats from different groups. Data are expressed as means ± SD (N=5). (e) H&E staining, Masson trichrome staining, as well as CD31 and HIF-1α immunofluorescence staining of the wound tissue sections of rats from different groups on day 3. Data are expressed as means ± SD (N=3). The green star represents the granulation tissue. (f)–(i) The quantification of granulation tissue (f), collagen deposition (g), microvascular area (h), and HIF-1α expression (i) from the images of the stained tissue sections. Data are expressed as means ± SD (N=3). Statistical significances were calculated via Student’s t-test. *P<0.05, **P<0.01, and ***P<0.001.

Fig. 6. Transcriptional mechanistic investigation of LEB@Cyan in chronic wound healing. (a) Schematic illustration of the mRNA-seq procedures. The figure was created by Figdraw. (b) PCA analysis of all genes assayed from wound tissues of rats from different groups. Data are shown as they are (N=3). (c) Heatmap distributions of DEGs associated with inflammatory pathways of wound tissues of rats from different groups. Data are shown as they are (N=3). (d) and (e) Volcano plots of the DEGs in the transcriptome of wound tissues of rats from the comparison of diabetic control versus normal (d) and LEB@Cyan (e) versus diabetic control. (f) Distributions of gene count in diabetic control versus normal for pairwise comparisons between LEB@Cyan versus diabetic control. (g) and (h) Bubble diagram of GO enrichment analysis of wound tissues of rats from the comparison of diabetic control versus normal (g) and LEB@Cyan (h) versus diabetic control.