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    Biomaterials

    Engineering the Granular Aerogel for Accelerated Diabetic Wound healing

    (C-119) Engineering the Granular Aerogel for Accelerated Diabetic Wound healing

    Thursday, October 12, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row C - Poster # 119

      Presenting Author(s)

    • Johnson V. John, Ph.D

      Terasaki Fellow
      Terasaki Institute for Biomedical Innovation
      Los Angeles, California, United States

      • Co-Author(s)

    • JX

      Jingwei Xie

      Professor
      University of Nebraska Medical Center
      Omaha, Nebraska, United States

    Introduction:: Through gas bubble-mediated co-axial electrospraying, we present a versatile method for the engineering of injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions. These nanofiber microspheres can also mimic extracellular matrix microarchitecture. Adjusting the processing parameters allowed for precisely manipulating the NMs' sizes and structures (1-3). These parameters included air flow rate, applied voltage, distance, and spinneret configuration in the co-axial setup. Importantly, in contrast to the method of self-assembly, this technique can fabricate NMs from any material that is amenable to electrospinning or any of the other techniques for the fabrication of nanofibers. The porous NMs have the potential to enhance guided cell migration during the regeneration of soft and hard tissues.

    Materials and Methods:: According to our previous the open porous architecture of NMs encouraged us to compare the wound healing capacity of porous and nonporous NMs. To facilitate that, we prepare PLGA:gelatin (1:1) short nanofiber composed of porous and non-porous NMs with our newly invented technology, co-axial electrospray with bubble technology (1-3). The parameters were the same as our previous report (Voltage = 6kV, airflow rate = 10 mL/h, nanofiber dispersion flow rate = 2 mL/h, and distance between the spinneret and collector = 10cm). The collected NMs were freeze-dried and followed by crosslinking in GA vapor-like in the previous report. The nonporous NMs were prepared by the same PLGA:gelatin (1:1) short nanofiber without a co-axial setup similar to our previous study.

    Results, Conclusions, and Discussions::

    We examined a variety of parameters like the flow rate of the air, the distance between the spinneret and collector, and voltage to tune the morphology and porosity of NMs. We have engineered PLGA:gelatin (1:1) short nanofiber composed of open porous NMs by our previously reported co-axial electrospray with bubble technology (1,2). The porosity and pore distribution were like our previous report at 6kV, 2 mg/mL flowrate (shell), and 10 mL/h airflow rate in core. The difference in morphologies could be due to the number of gas bubbles introduced within the droplets. At low airflow rates, bubbles could fuse and form a large bubble in the droplets with pressure too low to break the nanofiber shell before freezing in the liquid N2. Fig. 1a-d shows the representative H&E staining images from the diabetic mice after 7 and 14 days of treatments. Fig.a,b represents H&E staining images of the nonporous NMs treated diabetic mice, where the granulation tissues are formed around the NMs (yellow arrow). However, open porous NMs treated mice show significant cell penetration from the two sides and bottom of the wound. Fig. 1c-d represents the H&E staining images of the porous NMs treated diabetic mice. On day 7, we can observe the open porous structure in stained images (white circle), but on day 14, we observed many cells migrating throughout NMs (yellow arrow). The granulation tissues formed through the porous NMs to make a 3D tissue structure (yellow arrow), which is consistent with our subcutaneous study in rats. Moreover, more blood vessels are observed in the porous NMs treated mice samples (red arrows). Then we quantified the cell migration and neovascularization during the wound closure. Fig. 1e shows that ~80% of the wounds are closed by porous NMs treated mice compared to nonporous NMs treated mice (35%) in 14 days. In addition, more neovascularized sprouts are observed in the porous NMs treated diabetic mice (Fig. 1f). Therefore, we believe that the open porous structure of porous NMs will be a great choice not only for diabetic wounds but also for all wounds.



    Acknowledgements (Optional): : This work was supported by grants from the National Institute of General Medical Science (NIGMS) at the NIH (R01GM123081), and R01DK134903

    References (Optional): :

    (1) S. Boda et al. ACS Appl Mater Interfaces.2018;10:25069. (2) John JV et al. Nanomedicine: NBM. 2019;22;102081 (3) John JV et al. Small. 2020;16:1907393