2 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
Developing Hybrid Polymer Scaffolds Using Peptide Modified Biopolymers for Cell Implantation
Polymeric
scaffolds containing biomimics offer exciting therapies
with broad potential impact for cellular therapies and thereby potentially
improve success rates. Here we report the designing and fabrication
of a hybrid scaffold that can prevent a foreign body reaction and
maintain cell viability. A biodegradable acrylic based cross-linkable
polycaprolactone based polymer was developed and using a multihead
electrospinning station to fabricate hybrid scaffolds. This consists
of cell growth factor mimics and factors to prevent a foreign body
reaction. Transplantation studies were performed subcutaneously and
in epididymal fat pad of immuno-competent Balb/c mice and immuno-suppressed
B6 Rag1 mice and we demonstrated extensive neo-vascularization and
maintenance of islet cell viability in subcutaneously implanted neonatal
porcine islet cells for up to 20 weeks of post-transplant. This novel
approach for cell transplantation can improve the revascularization
and allow the integration of bioactive molecules such as cell adhesion
molecules, growth factors, etc