PLGA-PEG-Mal from PolySciTech used in development of immunosuppressant releasing tissue scaffold
One of the major challenges in stem-cell and tissue
engineering is rejection of the new cells by the body through the immune
system. Since systemic delivery of immunosuppressant medicines has severe side-effects,
a better solution is localized delivery of immunosuppressants to prevent the
cells in the scaffold from being attacked by immune cells. Recently, researchers
from Fudan University, Tianjin Medical University (China), and Ewha Women’s
University (Korea) used PLGA-PEG-Mal (PolyVivo AI136) from PolySciTech (www.polyscitech.com)
to create tacrolimus loaded PLGA-PEG- RADA16 self-attractive nanoparticles. These
were loaded into stem-cell hydrogels and remained within the hydrogel by
electrostatic attraction. This resulted in a consistent and controlled release
of immunosuppressant from the scaffold to prevent immune response against the
loaded stem cells. This research holds promise to improve results for a wide
array of tissue engineering applications. Read more: Li, Ruixiang, Jianming
Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, and Jianxin
Wang. "Sustained Release of Immunosuppressant by Nanoparticle-anchoring
Hydrogel Scaffold Improved the Survival of Transplanted Stem Cells and Tissue
Regeneration." Theranostics 2018; 8(4): 878-893. doi: 10.7150/thno.22072 http://www.thno.org/v08p0878.pdf
“The outcome of
scaffold-based stem cell transplantation remains unsatisfied due to the poor
survival of transplanted cells. One of the major hurdles associated with the
stem cell survival is the immune rejection, which can be effectively reduced by
the use of immunosuppressant. However, ideal localized and sustained release of
immunosuppressant is difficult to be realized, because it is arduous to hold
the drug delivery system within scaffold for a long period of time. In the
present study, the sustained release of immunosuppressant for the purpose of
improving the survival of stem cells was successfully realized by a
nanoparticle-anchoring hydrogel scaffold we developed. Methods: Poly
(lactic-co-glycolic acid) (PLGA) nanoparticles were modified with RADA16
(RNPs), a self-assembling peptide, and then anchored to a RADA16 hydrogel (RNPs
+ Gel). The immobilization of RNPs in hydrogel was measured in vitro and in
vivo, including the Brownian motion and cumulative leakage of RNPs and the in
vivo retention of injected RNPs with hydrogel. Tacrolimus, as a typical immunosuppressant,
was encapsulated in RNPs (T-RNPs) that were anchored to the hydrogel and its
release behavior were studied. Endothelial progenitor cells (EPCs), as model
stem cells, were cultured in the T-RNPs-anchoring hydrogel to test the
immune-suppressing effect. The cytotoxicity of the scaffold against EPCs was
also measured compared with free tacrolimus-loaded hydrogel. The therapeutic
efficacy of the scaffold laden with EPCs on the hind limb ischemia was further
evaluated in mice. Results: The Brownian motion and cumulative leakage of RNPs
were significantly decreased compared with the un-modified nanoparticles (NPs).
The in vivo retention of injected RNPs with hydrogel was obviously longer than
that of NPs with hydrogel. The release of tacrolimus from T-RNPs + Gel could be
sustained for 28 days. Compared with free tacrolimus-loaded hydrogel, the
immune responses were significantly reduced and the survival of EPCs was
greatly improved both in vitro and in vivo. The results of histological
evaluation, including accumulation of immune cells and deposition of anti-graft
antibodies, further revealed significantly lessened immune rejection in
T-RNPs-anchoring hydrogel group compared with other groups. In pharmacodynamics
study, the scaffold laden with EPCs was applied to treat hind limb ischemia in
mice and significantly promoted the blood perfusion (~91 % versus ~36 % in
control group). Conclusion: The nanoparticle-anchoring hydrogel scaffold is
promising for localized immunosuppressant release, thereby can enhance the
survival of transplanted cells and finally lead to successful tissue
regeneration. Key words: stem cell; immune suppression; tacrolimus;
nanoparticles; endothelial progenitor cells; RADA16 hydrogel.”
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