Speaker
Description
"Introduction: Human umbilical cord blood stored in blood banks cannot always be used for hematopoietic stem cell transplantation as up to 80% of stem cells are lower than the cut-off required for such application, being potentially available for non-transfusion applications such as the source of platelet growth factor [1]. In this study, we fabricated a fibrin-based drug delivery system to provide a local and sustained release of cord blood platelet lysate (CBPL) at the wound site. Also, we assessed the temporal evolution of skin lesions using photoacoustic imaging (PAI) and near-infrared spectroscopy (NIRS), non-invasive technologies translatable to a clinical setting. [2,3]
Methods: Fibrin scaffold loaded with CBPL was fabricated by a peculiar spray process (IT Patent application pending N. 102021000025664). Excision wounds were created on the dorsum of genetic diabetic mice (db/db) using a biopsy punch (8 mm diameter). Wounds were treated with fibrin scaffolds with or without CBPL. Oxygen saturation (%SO2) was monitored in the wound area and surrounding tissue through PAI and NIRS imaging on days 0, 7, and 14 after lesion induction. At each time point, whole blood was collected for flow cytometry, and on day 14 wound tissue was retrieved for histological analyses.
Results: Diabetic mice treated with CBPL scaffold showed a significantly higher closure of about 82% of the initial lesion size, 14 days after the intervention. Animals treated with the unloaded scaffolds showed closure of only 62% of the initial lesion size. Histological analysis demonstrated an improved reepithelization and collagen deposition in granulation tissue in mice treated with CBLP scaffold in comparison to unloaded fibrin scaffold. The flow cytometric quantification of circulating fraction variations (compared to baseline) of endothelial progenitor cells (EPCs, CD45-/CD34+/KDR+) showed an increase in the CBPL fibrin scaffold treated mice when compared with the fibrin scaffold alone. Moreover, a statistically significant correlation (P = 0.03, R = 0.754) has been observed on day 14 after induction of skin lesion between wound repair areas and the variations of EPCs fraction in the CBPL fibrin scaffold treated mice. In all the lesions, the %SO2 signal from both PAI and NIRS showed a typical trend characterized by an increase one week after the wound induction (day 7) followed by a decrease toward the initial intact skin %SO2 values (day14).
Conclusions: This study allows developing a new approach based on imaging and circulating biomarkers to describe the inflammatory state and healing dynamics during the regenerative process. The present findings pave the way for clinical translation of the developed experimental patches and combined molecular imaging.
[1] Eppley BL et al. Plast Reconstr Surg. 114(6), 1502-8 (2004)
[2] Steinberg, et al., Photoacoustics. 14, 77–98 (2019)
[3] Landsman A. Wounds. 32(10), 265-271 (2020)
Acknowledgments: This work was supported by Fondazione Pisa grant number No. 2016.0163, Project acronym: PREVISION. The project has been supported by the Multi-Modal Molecular Imaging Italian node - Euro Bioimaging (MMMI- EuBi)."
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