Molecular Retention Limitations for Prevascularized Subcutaneous Sites for Islet Transplantation.

Autor:	Waduthanthri KD; Department of Chemical and Materials Engineering, Donadeo Innovation Centre for Engineering, University of Alberta, 9211-116 Street NW, Edmonton, AB T6G 1H9, Canada., Kuppan P; Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 1H9, Canada.; Alberta Diabetes Institute, Li Ka Shing Centre for Research, 112th Street, Edmonton, AB T6G 2E1, Canada., Korbutt GS; Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 1H9, Canada.; Alberta Diabetes Institute, Li Ka Shing Centre for Research, 112th Street, Edmonton, AB T6G 2E1, Canada., Pepper AR; Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 1H9, Canada.; Alberta Diabetes Institute, Li Ka Shing Centre for Research, 112th Street, Edmonton, AB T6G 2E1, Canada., Unsworth LD; Department of Chemical and Materials Engineering, Donadeo Innovation Centre for Engineering, University of Alberta, 9211-116 Street NW, Edmonton, AB T6G 1H9, Canada.
Jazyk:	angličtina
Zdroj:	Biomacromolecules [Biomacromolecules] 2024 Mar 11; Vol. 25 (3), pp. 1439-1447. Date of Electronic Publication: 2024 Feb 13.
DOI:	10.1021/acs.biomac.3c00977
Abstrakt:	Beta cell replacement therapies utilizing the subcutaneous space have inherent advantages to other sites: the potential for increased accessibility, noninvasive monitoring, and graft extraction. Site prevascularization has been developed to enhance islet survivability in the subcutaneous zone while minimizing potential foreign body immune responses. Molecular communication between the host and prevascularized implant site remains ill-defined. Poly(ethylene oxide)s (PEOs) of various hydrated radii (i.e., ∼11-62 Å) were injected into prevascularized subcutaneous sites in C57BL/6 mice, and the clearance and organ biodistribution were characterized. Prevascularization formed a barrier that confined the molecules compared with the unmodified site. Molecular clearance from the prevascularized site was inversely proportional to the molecular weight. The upper limit in molecular size for entering the vasculature to be cleared was determined to be 35 kDa MW PEO. These findings provide insight into the impact of vascularization on molecular retention at the injection site and the effect of molecular size on the mobility of hydrophilic molecules from the prevascularized site to the host. This information is necessary for optimizing the transplantation site for increasing the beta cell graft survival.
Databáze:	MEDLINE
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