Biomedical Engineering Reference
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cells (rBMSCs). They demonstrated that rBMSCs seeded onto the surface of the scaffolds
differentiated into osteoblasts when cultured in the presence of Dex-loaded CMCht/PAMAM
nanoparticles. They confirmed that Dex-loaded CMCht/PAMAM nanoparticles combined
with hydroxyapatite augmented osteogenesis by increasing ALP activity and mineralization of
the extracellular matrix. The pre-incubation process confirmed by this study allowed the
delivery of Dex inside the cells and directly influenced their cellular differentiation, which indi-
cated its appropriateness for tissue engineering.
Pimpha et al . [40] developed a nanocarrier for plasmid DNA by PEI-introduced CS
nanoparticles for rat MSCs. The CS/PEI nanoparticles were prepared by the emulsion poly-
merization of a methyl methacrylate monomer in the presence of different concentrations
of PEI mixed with CS. The introduction of PEI affected the surface charge, dispersing
stability and buffering capacity of the nanoparticles from the viewpoint of the gene trans-
fection carrier. Gene transfection and the prolonged time period of expression of CS/PEI
nanoparticles for MSCs were achieved with greater efficiency than that of CS and
lipofectamine. They have concluded that the combination of CS and PEI on the nanopar-
ticles is promising as gene delivery nanocarriers for MSCs.
Hyaluronic Acid
Hyaluronan or HA has been used to modify the dispersing stability, surface charge, and
buffering capacity of polymers such as PEI [43] to form nanoparticles for nonviral gene
delivery. Nanoparticles made of HA and CS showed lower cytotoxicity and induced a higher
rate of gene integration in NSCs and spinal cord slice tissue compared to those obtained
with PEI.
Mikos et al . [43] prepared branched PEI (bPEI) and HA as a nanocarrier for plasmid
DNA in order to improve transfection of bPEI into hMSCs. The bPEI-HA nanocarrier
formed a zwitterionic polymer capable of inter- and intramolecular interactions. The hMSCs
transfected with smaller complexes showed a significant increase in transfection and bPEI-
HA performed significantly better than bPEI in terms of cell viability and maximum trans-
fection efficiencies. Therefore, modifying bPEI by covalent conjugation with HA enhanced
its performance as a gene-delivery nanocarrier in hMSCs.
Also Mahor et al . [14] encapsulated plasmid DNA into HA biomaterials by using
bPEI as a transfecting agent to produce a nonviral gene delivery nanocarrier for MSCs.
The DNA-HA nanoparticles were formulated by ionic gelation followed by the cross-
linking method with high encapsulation efficiency. Hyaluronic acid nanoparticles
provided a surface for sustained release of DNA, thereby inducing transgene expression
for a period of one month. The results of cellular localization studies illustrated that
nanocarriers were rapidly internalized by the cells through nonspecific endocytosis.
Consequently, long-term expression of the desired protein could be achieved with a
smaller amount of DNA required.
Poly(disulfide amine)
Branched poly(disulfide amine) (B-PDA) is a bioreducible cationic polymer that contains
disulfide bonds in its backbone which are capable of forming a nanocarrier for efficient
intracellular delivery into the stem cell. This polymer with its flexible cationic amino
branches can complex with a gene/siRNA and have a high proton-buffering capacity for
efficient endosomal escape. Poly(disulfide amine) because of rapid degradation of disulfide
bonds in the reductive environment facilitates release of siRNA in the cytoplasm. Also, it
has a low toxicity and efficient body clearance owing to its efficient biodegradation [44].
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