Glycosaminoglycan-based hybrid hydrogel encapsulated with polyelectrolyte complex nanoparticles for endogenous stem cell regulation in central nervous system regeneration.

The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response, lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1α (SDF-1α) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to amplify the signaling of SDF-1α and bFGF to regulate NSC in vitro. In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis. These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules.

Role of long noncoding RNA ZFAS1 in proliferation, apoptosis and migration of chondrocytes in osteoarthritis.

OBJECTIVE: This study aimed to investigate the role of long noncoding RNA (lncRNA) ZFAS1 in the development of osteoarthritis (OA) as well as to explore the potential molecular mechanisms. MATERIAL AND METHODS: The expression of lncRNA ZFAS1 in OA chondrocytes was determined. After cell transfection, the effects of ZFAS1 overexpression on the viability, proliferation, apoptosis and migration of OA chondrocytes were detected. Additionally, the expression levels of Bcl-2, Bax, Caspase-3, and matrix metalloproteinases (MMP1 and MMP13) were determined. The expressions of Wnt3a signaling proteins, and the relationship between ZFAS1 and Wnt3a were detected as well. RESULTS: The expression of ZFAS1 was down-regulated in OA chondrocytes compared with normal chondrocytes. Overexpression of ZFAS1 promoted the viability, proliferation and migration, and inhibited apoptosis and matrix synthesis of OA chondrocytes. Additionally, overexpressed ZFAS1 significantly decreased Wnt3a factors. The effects of ZFAS1 on OA chondrocytes were achieved by regulating Wnt3a signaling. CONCLUSIONS: Our study demonstrates that ZFAS1 may promote chondrocyte proliferation, and migration, and decrease apoptosis and matrix synthesis in OA possible via targeting Wnt3a signaling. ZFAS1 provides a potential therapeutic target for OA treatment.

[PROXIMAL FIBULAR OSTEOTOMY COMBINED WITH ARTHROSCOPIC DEBRIDEMENT FOR TREATING MEDIAL KNEE OSTEOARTHRITIS WITH VARUS].

OBJECTIVE: To evaluate the effectiveness of proximal fibular osteotomy combined with arthroscopic debridement in the treatment of medial knee osteoarthritis with varus. METHODS: Between December 2013 and June 2015, 61 patients with medial knee osteoarthritis with varus were treated by arthroscopic debridment in 32 cases (group A) and by proximal fibular osteotomy combined with arthroscopic debridement in 29 cases (group B). No significant difference was found in gender, age, side, disease duration, OA stage, visual analogue scale (VAS) score, and knee society score (KSS) between 2 groups (P>0.05). The clinical outcome was evaluated by VAS score and KSS score at 1 week, 3 months, and 12 months after operation. RESULTS: The patients in 2 groups were followed up 12 months. All incisions healed by first intention. There was no significant difference in complication incidence between groups A and B (0 vs. 3.4%; χ2=0.723, P=0.432). The VAS scores were significantly decreased at 1 week, 3 months, and 12 months after operation when compared with preoperative score in 2 groups (P<0.05). The VAS score of group A was significantly lower than that of group B at 1 week after operation (P<0.05), but the VAS score of group A was significantly higher than that of group B at 3 months, and 12 months after operation (P<0.05). The knee function was obviously improved in 2 groups, and the KSS scores at 1 week, 3 months and 12 months after operation were significantly better than preoperative score (P<0.05). The KSS score of group A was significantly lower than that of group B at 3 months, and 12 months after operation (P<0.05). CONCLUSIONS: Proximal fibular osteotomy combined with arthroscopic debridement can treat knee malalignment and disease in knee, it is an effective and safe method to treat the medial knee osteoarthritis with varus.

Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal Cancer Therapy.

Indocyanine green (ICG), an FDA approved medical near-infrared (NIR) imaging agent, has been extensively used in cancer theranosis. However, the limited aqueous photostability, rapid body clearance, and poor cellular uptake severely restrict its practical applications. For these problems to be overcome, ICG-encapsulated hybrid polymeric nanomicelles (PNMs) were developed in this work through coassociation of the amphiphilic diblock copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and hydrophobic electrostatic complexes composed of ICG molecules and branched poly(ethylenimine) (PEI). The ICG-encapsulated hybrid PNMs featured a hydrophobic PLGA/ICG/PEI core stabilized by hydrophilic PEG shells. The encapsulation of electrostatic ICG/PEI complexes into the compact PLGA-rich core not only facilitated the ICG loading but also promoted its aqueous optical stability. The effects of the chain length of PEI in combination with ICG on the physiochemical properties of PNMs and their drug leakage were also investigated. PEI(10k) (10 kDa) could form highly robust and dense complexes with ICG, and thus prominently reduced ICG outflow from the PNMs. The results of in vitro cellular uptake and cytotoxicity studies revealed that the ICG/PEI(10k)-loaded PNMs significantly promoted cellular uptake of ICG by HeLa cells due to their near-neutral surface, and thereby augmented the NIR-triggered hyperthermia effect in destroying cancer cells. These findings strongly indicate that the ICG/PEI10k-loaded PNMs have significant potential for attaining effective cancer imaging and photothermal therapy.