Animals and treatments
Three-month-old female or male C57BL/6 mice were used. The procedures for the generation of streptozotocin-induced diabetic mice and establishment of full-thickness excisional cutaneous wounds (6 mm in diameter) in diabetic mice and skin burn wounds (1 cm in diameter) in normal mice were detailed in our recently published studies (24, 25). Then, L-AgÅPs-gel, AgNPs-gel, or blank-gel were smeared daily around and on the surfaces of diabetic and burn wounds (10 mice for each group). These gels could be spread easily and evenly over the surface of the skin, resulting in a thin layer of gel on the wound surface. Images of wounds at the indicated time points were captured. The diameters of wounds were measured using a caliper rule, and wound closure rates were calculated as follows: wound closure rate (%) = (Ao − At)/Ao × 100, where Ao indicated the original size of wound and At represented the diameter of wounds at the indicated times. The time for complete wound closure was recorded in male mice with diabetic or burn wounds. At day 11 (for female mice with diabetic wounds) or day 13 (for female mice with burn wounds) after wounding, three mice in each group were killed, and the wound bed with adjacent healthy skin tissues (1 cm by 1 cm square areas centered at the wound) were collected for counting bacteria. The remaining mice were killed after collecting blood by eyeball enucleation. For diabetic mice, a 200-μL blood sample for each mouse was subjected to routine blood test. Serum was separated from the remaining blood by centrifugation for 15 min at 1000g and subjected to hepatic and renal function tests. These tests were conducted on automated instruments in the Department of Clinical Laboratory in Xiangya Hospital. The diabetic and burn wounds tissues were harvested as described above and processed for histological, immunohistochemical, and immunofluorescent analyses.
REFERENCES AND NOTES
24. H. Yin, C.-Y. Chen, Y.-W. Liu, Y.-J. Tan, Z.-L. Deng, F. Yang, F.-Y. Huang, C. Wen, S.-S. Rao, M.-J. Luo, X.-K. Hu, Z.-Z. Liu, Z.-X. Wang, J. Cao, H.-M. Liu, J.-H. Liu, T. Yue, S.-Y. Tang, H. Xie, Synechococcus elongatus PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis. Theranostics 9, 2678–2693 (2019).
25. C.-Y. Chen, S.-S. Rao, L. Ren, X.-K. Hu, Y.-J. Tan, Y. Hu, J. Luo, Y.-W. Liu, H. Yin, J. Huang, J. Cao, Z.-X. Wang, Z.-Z. Liu, H.-M. Liu, S.-Y. Tang, R. Xu, H. Xie, Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 8, 1607–1623 (2018).