Dexamethasone-Loaded Hydrogels Improve Motor and Cognitive Functions in a Rat Mild Traumatic Brain Injury Model.

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model.

Hydrogel-mediated local delivery of dexamethasone reduces neuroinflammation after traumatic brain injury.

Excessive and prolonged neuroinflammation leads to neuronal cell death and limits functional recovery after traumatic brain injury (TBI). Dexamethasone (DX) is a steroidal anti-inflammatory agent that is known to attenuate early expression of pro-inflammatory cytokines associated with activated microglia/macrophages. In this study, we investigated the effect of dexamethasone-conjugated hyaluronic acid (HA-DXM) incorporated in a hydrolytically degradable, photo-cross-linkable poly (ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogel on the inflammatory response, apoptosis, and functional recovery in a controlled cortical impact (CCI) rat TBI model.

Combinatorial therapy of sirolimus and heparin by nanocarrier inhibits restenosis after balloon angioplasty .

To develop poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) as a dual drug-delivery carrier for sirolimus (SR) and heparin (Hep) to inhibit restenosis after balloon angioplasty. SR was loaded in the hydrophobic core and negatively charged Hep complexed with the positively charged hydrophilic shell of PgP. SR- and Hep-loaded PgP was tested on rat aortic smooth muscle cells and injured porcine coronary arteries after balloon angioplasty .

Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures.

The surgical connection of blood vessels, anastomosis, is a critical procedure in many reparative, transplantation, and reconstructive surgical procedures. However, effective restoration of circulation is complicated by pathological clotting (thrombosis) or progressive occlusion due to excess cell proliferation that often leads to additional surgeries and increases morbidity and mortality risk for patients. Pharmaceutical agents have been tested to prevent these complications, but many have unacceptable systemic side effects.

Physicochemical stability and transfection efficiency of cationic amphiphilic copolymer/pDNA polyplexes for spinal cord injury repair.

Multiple age-related and injury-induced characteristics of the adult central nervous system (CNS) pose barriers to axonal regeneration and functional recovery following injury. In situ gene therapy is a promising approach to address the limited availability of growth-promoting biomolecules at CNS injury sites. The ultimate goal of our work is to develop, a cationic amphiphilic copolymer for simultaneous delivery of drug and therapeutic nucleic acids to promote axonal regeneration and plasticity after spinal cord injury.

Cationic, amphiphilic copolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord.

Unlabelled: Spinal cord injury commonly leads to permanent motor and sensory deficits due to the limited regenerative capacity of the adult central nervous system (CNS). Nucleic acid-based therapy is a promising strategy to deliver bioactive molecules capable of promoting axonal regeneration. Branched polyethylenimine (bPEI: 25kDa) is one of the most widely studied nonviral vectors, but its clinical application has been limited due to its cytotoxicity and low transfection efficiency in the presence of serum proteins.

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells.

Scaffold-based delivery of bioactive molecules capable of directing stem cell differentiation is critical to the development of point-of-care cell therapy for orthopedic repair. Dexamethasone-conjugated hyaluronic acid (HA-DXM) was synthesized and combined with hydrolytically degradable, photo-cross-linkable PEG-bis(2-acryloyloxy propanoate) (PEG-bis-AP) to form semi-IPNs. Dexamethasone (DX) release was limited in physiological buffer and substantially increased in the presence of encapsulated human mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming that release occurred primarily by a cell-mediated enzymatic mechanism.

Poly(ethylene glycol) diacrylate/hyaluronic acid semi-interpenetrating network compositions for 3-D cell spreading and migration.

To serve as artificial matrices for therapeutic cell transplantation, synthetic hydrogels must incorporate mechanisms enabling localized, cell-mediated degradation that allows cell spreading and migration. Previously, we have shown that hybrid semi-interpenetrating polymer networks (semi-IPNs) composed of hydrolytically degradable poly(ethylene glycol) diacrylates (PEGdA), acrylate-PEG-GRGDS and native hyaluronic acid (HA) support increased cell spreading relative to fully synthetic networks that is dependent on cellular hyaluronidase activity. This study systematically investigated the effects of PEGdA/HA semi-IPN network composition on 3-D spreading of encapsulated fibroblasts, the underlying changes in gel structure responsible for this activity, and the ability of optimized gel formulations to support long-term cell survival and migration.

Glycosylation-related genes in NS0 cells are insensitive to moderately elevated ammonium concentrations.

NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. To improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. While ammonium has been shown to adversely affect glycosylation-related gene expression in CHO cells, NS0 studies have not been performed.

Efficacy and mechanism of poloxamine-assisted polyplex transfection.

Background: Amphiphilic block copolymers acting as biological response modifiers provide an attractive approach for improving the transfection efficiency of polycationic polymer/DNA complexes (polyplexes) by altering cellular processes crucial for efficient transgene expression.

Methods: The present study aimed to investigate the effect of the poloxamine Tetronic T904, a four-arm polyethylene oxide/polypropylene oxide block copolymer, on polyplex transfection and to determine its mechanism of action by analyzing the cellular uptake of polyplex, the nuclear localization of plasmid and RNA transcript production.

Results: T904 significantly increased the transfection efficiency of polyplexes based on 25-kDa branched polyethylenimine in a dose-dependent manner in the presence of serum in C6 glioma cells, as well as human fibroblasts and mesenchymal stem cells.