In-situ forming injectable GFOGER-conjugated BMSCs-laden hydrogels for osteochondral regeneration.

The collagen-mimetic peptide GFOGER possesses the chondrogenic potential and has been used as a cell adhesion peptide or chondrogenic inducer. Here, we prepared an injectable in situ forming composite hydrogel system comprising methoxy polyethylene glycol-b-polycaprolactone (MPEG-PCL) and GFOGER-conjugated PEG-PCL (GFOGER-PEG-PCL) with various GFOGER concentrations based on our recently patented technology. The conjugation of GFOGER to PEG-PCL was confirmed by 1H NMR, and the particle size distribution and rheological properties for the sol-gel transition behavior of the samples with respect to the GFOGER content were evaluated systemically. In vitro experiments using rat bone marrow-derived mesenchymal stem cells (BMSCs) revealed that the GFOGER-PEG-PCL hydrogel significantly enhanced expression of integrins (ß1, α2, and α11), increased expression of FAK, and induced downstream signaling of ERK and p38. Overexpression of chondrogenic markers suggested that BMSCs have the potential to differentiate into chondrogenic lineages within GFOGER-PEG-PCL samples. In vivo studies using a rat osteochondral defect model revealed that transplanted BMSCs with GFOGER0.8-PEG-PCL survived at the defect with strong chondrogenic expression after 4 weeks. The stem cell-laden GFOGER0.8-PEG-PCL hydrogel produced remarkable osteochondral regeneration at 8 weeks of transplantation, as determined by histological findings and micro-CT analysis. The histomorphological score in the GFOGER0.8-PEG-PCL + BMSCs group was ~1.7-, 2.6-, and 5.3-fold higher than that in the GFOGER0.8-PEG-PCL, MPEG-PCL, and defect groups, respectively. Taken together, these results provide an important platform for further advanced GFOGER-based stem cell research for osteochondral repair.

Stem cell laden nano and micro collagen/PLGA bimodal fibrous patches for myocardial regeneration.

BACKGROUND: Although the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering . METHODS: Nano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated. RESULTS: Nano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings. CONCLUSION: Col/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

Theranostic potential of biodegradable polymeric nanoparticles with paclitaxel and curcumin against breast carcinoma.

In this study, integrin-mediated targeting and near-infrared fluorescence (NIRF) traceable polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-PLGA)-based polymeric nanoparticles (NPs) were prepared to investigate the effects of paclitaxel (PTX) and curcumin (CUR) combination therapy on breast cancer. Cyclic (arginine-glycine-aspartic acid-phenylalanine-lysine) (cRGDfK) was selected as a ligand for breast cancer and conjugated to the end of NPs (cRGDfK-NPs). For fluorescence imaging, sulfo-cyanine 5.5 (Cy5.5) was incorporated into NPs (Cy5.5-NPs). A series of hybrid NPs consisting of NPs, cRGDfK-NPs, and Cy5.5-NPs with drugs encapsulated inside the core (Cy5.5-cRGDfK-NPs/PTX + CUR) were prepared by self-assembly. The efficacy of PTX and CUR combination and the ability of the integrin-mediated targeting of NPs were systemically investigated using a 4T1 mouse breast cancer cell line and a nude mouse xenograft model. We suggested that Cy5.5-cRGDfK-NPs/PTX + CUR has superior theranostic potential against breast carcinoma.

Injectable hydrogels based on MPEG-PCL-RGD and BMSCs for bone tissue engineering.

The aim of this study was to investigate the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) seeded on novel thermosensitive in situ forming hydrogel systems comprising methoxy polyethylene glycol-polycaprolactone (MP) and RGD-conjugated MP (MP-RGD) in vitro and in vivo. Real-time polymerase chain reaction (PCR) together with immunofluorescence staining revealed the strong expression of osteogenic markers (collagen 1 and osteocalcin) of BMSCs in MP/MP-RGD samples compared to MP samples. PCR array testing also showed the upregulation of the interconnected signaling networks regulating cell proliferation and differentiation, which was further verified through the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Histological findings and computed tomographic analysis demonstrated that the MP/MP-RGD hydrogel dramatically promoted new bone formation in a rabbit calvarial defect model. In conclusion, this hydrogel appears to elicit cellular behaviors desired for bone tissue regeneration.