1 research outputs found
Molecular Retention Limitations for Prevascularized Subcutaneous Sites for Islet Transplantation
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