Esmaiel Jabbari

Swelling behavior of acrylic acid hydrogels prepared by γ-radiation crosslinking of polyacrylic acid in aqueous solution

Abstract Swelling behavior of anionic acrylic acid polyelectrolyte hydrogel synthesized by γ-radiation crosslinking of polyacrylic acid in aqueous solution was investigated. Cross-linked polyacrylic acid (PAA) hydrogel was synthesized using a two-step method. First, uncrosslinked PAA was synthesized by free-radical precipitation polymerization of acrylic acid in benzene. In the second step, PAA was dissolved in aqueous solution, and it was crosslinked with γ-irradiation. The swelling behavior of the gels was studied as a function of the concentration of PAA in aqueous solution during γ-irradiation, radiation dose, and pH of the swelling medium. In a buffered solution of pH 4, the degree of swelling ranged from 30 to 300 for irradiation doses ranging from 5 to 25 kGy, and the swelling was Fickian. On the other hand, in a buffered solution of pH 7 the degree of swelling ranged from 80 to 500 depending on the irradiation dose and the swelling was non-Fickian.

Evidence of mucoadhesion by chain interpenetration at a poly (acrylic acid)/mucin interface using ATR-FTIR spectroscopy

Poly (acrylic acid) is considered to be an important mucoadhesive for controlled release applications. Yet, the specific mechanisms responsible for its bioadhesive behavior are not well understood. Attenuated total reflection infrared spectroscopy (ATR-FTIR) was developed for investigation of chain interpenetration at a poly (acrylic acid) (PAA) and mucin interface. A thin film of acrylic acid, polymerized below the gelation point, was cross-linked directly on an ATR crystal. The cross-linked PAA film was contacted with a buffered mucin solution and the ATR-FTIR spectrum was collected in situ as a function of time. The experimental results show evidence in support of chain interpenetration at the PAA/mucin interface. The experimental results indicate that as PAA and mucin are compatible in the 5–7 pH range, an important mechanism of mucoadhesion is the swelling of PAA by mucin and adhesion is limited by the extent of chain interpenetration across the biointerface.

Regulation of Osteogenic Differentiation of Rat Bone Marrow Stromal Cells on 2D Nanorod Substrates

Bone marrow stromal cells (BMSCs) possess multi-lineage differentiation potential and can be induced to undergo differentiation into various cell types with the correct combination of chemical and environmental factors. Although, they have shown great prospects in therapeutic and medical applications, less is known about their behavior on nanosurfaces mimicking the extra cellular matrix (ECM). In this report we have employed 2D substrates coated with tobacco mosaic virus (TMV) nanorods to study the differentiation process of BMSCs into osteoblast like cells. TMV is a rod-shaped plant virus with an average length of 300 nm and diameter of 18 nm. The osteogenic differentiation of BMSCs on TMV was studied over time points of 7, 14 and 21 days. We examined the temporal gene expression changes during these time points by real-time quantitative PCR (RT-qPCR) analysis. As expected, osteo-specific genes (osteocalcin, osteopontin and osteonectin) were upregulated and showed a maximum change in expression on TMV at 14 days which was 7 days earlier than on tissue culture plastic (TCP). Based on the genes expression profile generated by RT-qPCR experiments, we proposed that the early interaction of cells with TMV triggers on signaling pathways which regulate speedy expression of osteocalcin in turn, resulting in early mineralization of the cells. To further investigate these regulating factors we studied global changes in gene expression (DNA microarray analyses) during osteogenic differentiation on the nanosubstrate. Multitudes of genes were affected by culturing cells on nanorod substrate, which corroborated our initial PCR findings. Microarray analysis further revealed additional targets influenced by the presence of nanorods on the surface, of which, the expression of bone morphogenetic protein 2 (BMP2) was of particular interests. Further investigation into the temporal change of BMP2, revealed that it acts as a major promoter in signaling the early regulation of osteocalcin on TMV coated substrates.

Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies.

Tissue engineering approaches to spinal cord injury (SCI) treatment are attractive because they allow for manipulation of native regeneration processes involved in restoration of the integrity and function of damaged tissue. A clinically relevant spinal cord regeneration animal model requires that the model mimics specific pathologic processes that occur in human SCI. This manuscript discusses issues related to preclinical testing of tissue engineering spinal cord regeneration strategies from a number of perspectives. This discussion includes diverse causes, pathology and functional consequences of human SCI, general and species related considerations, technical and animal care considerations, and data analysis methods.

Nanoscale tissue engineering: spatial control over cell-materials interactions

Cells interact with the surrounding environment by making tens to hundreds of thousands of nanoscale interactions with extracellular signals and features. The goal of nanoscale tissue engineering is to harness these interactions through nanoscale biomaterials engineering in order to study and direct cellular behavior. Here, we review two- and three-dimensional (2- and 3D) nanoscale tissue engineering technologies, and provide a holistic overview of the field. Techniques that can control the average spacing and clustering of cell adhesion ligands are well established and have been highly successful in describing cell adhesion and migration in 2D. Extension of these engineering tools to 3D biomaterials has created many new hydrogel and nanofiber scaffold technologies that are being used to design in vitro experiments with more physiologically relevant conditions. Researchers are beginning to study complex cell functions in 3D. However, there is a need for biomaterials systems that provide fine control over the nanoscale presentation of bioactive ligands in 3D. Additionally, there is a need for 2- and 3D techniques that can control the nanoscale presentation of multiple bioactive ligands and that can control the temporal changes in the cellular microenvironment.

MORPHOLOGY OF AND RELEASE BEHAVIOR FROM POROUS POLYURETHANE MICROSPHERES

A novel biomaterial application of porous microspheres is for sustained delivery of biologically active agents. Recent studies have pointed out the importance of biomaterial porosity in promoting biocompatibility and controlling release rate of active agents. The objective of this research was to investigate the effect of chain-extending agent on the porosity and release behavior of polyurethane (PU) microspheres prepared using a two-step suspension polycondensation method with methylene diphenyl diisocyanate (MDI) as the isocyanate, polyethylene glycol (PEG400) as the diol, and 1,4-butanediol as the chain-extending agent. Chain-extending agent was used to increase the ratio of hard to soft segments of the PU network, and its effect on microsphere morphology was studied with scanning electron microscopy. According to the results, porosity was significantly affected by the amount of chain-extending agent. The pore size decreased as the concentration of chain-extending agent increased from zero to 50 mole%. With further increase of chain-extending agent to 60 and 67%, PU chains became stiffer and formation of pores was inhibited. Therefore, pore morphology was significantly affected by variations in the amount of chain-extending agent. The release behavior of microspheres was investigated with diazinon as the active agent. After an initial burst, corresponding to 3% of the incorporated amount of active agent, the release rate was zero order.

Liposome encapsulation of curcumin: Physico-chemical characterizations and effects on MCF7 cancer cell proliferation

The role of curcumin (diferuloylmethane), for cancer treatment has been an area of growing interest. However, due to its low absorption, the poor bioavailability of curcumin limits its clinical use. In this study, we reported an approach of encapsulation a curcumin by nanoliposome to achieve an improved bioavailability of a poorly absorbed hydrophobic compound. We demonstrated that liposomal preparations to deliver curcumin increase its bioavailability. Liposomes composed of salmons lecithin also improved curcumin bioavailability compared to those constituted of rapeseed and soya lecithins. A real-time label-free cell analysis system based on real-time cell impedance monitoring was used to investigate the in vitro cytotoxicity of liposomal preparations.

Bioconjugation of hydrogels for tissue engineering

Success of tissue engineered constructs in regenerative medicine is limited by the lack of cellmatrix interactions to guide devleopment of the seeded cells into the desired tissue. This review highlights the most exciting developments in bioconjugation of synthetic hydrogels targeted to tissue engineering. Application of conjugation techniques has resulted in the synthesis of novel biomimetic cell-responsive hydrogels to control the cascade of cell migration, adhesion, survival, differentiation, and maturation to the desired lineage concurrent with matrix remodeling. The future outlook includes developing conjugated patterned hydrogel matrices, developing novel hydrogel matrices to support self-renewal and pluripotency of embryonic and adult stem cells, and merging 3D printing with bioconjugation to fabricate hydrogels with anatomical arrangement of cells and biomolecules.

Material Properties and Osteogenic Differentiation of Marrow Stromal Cells on Fiber-Reinforced Laminated Hydrogel Nanocomposites

The fibrils in the bone matrix are glued together by extracellular matrix proteins to form laminated structures (osteons) to provide elasticity and a supportive substrate for osteogenesis. The objective of this work was to investigate material properties and osteogenic differentiation of bone marrow stromal (BMS) cells seeded on osteon-mimetic fiber-reinforced hydrogel/apatite composites. Layers of electrospun poly(l-lactide) fiber mesh coated with a poly(lactide-co-ethylene oxide fumarate) (PLEOF) hydrogel precursor solution were stacked and pressed together, and crosslinked to produce a laminated fiber-reinforced composite. Hydroxyapatite (HA) nanocrystals were added to the precursor solution to produce an osteoconductive matrix for BMS cells. Acrylamide-terminated Arg-Gly-Asp (RGD) peptide (Ac-GRGD) was conjugated to the PLEOF/HA hydrogel phase to promote focal point adhesion of BMS cells. Laminates were characterized with respect to the Youngs modulus, degradation kinetics and osteogenic differentiation of BMS cells. The moduli of the laminates under dry and wet conditions were significantly higher than those of the fiber mesh and PLEOF/HA hydrogel, and within the range of values reported for wet human cancellous bone. At days 14 and 21, alkaline phosphatase (ALPase) activity of the laminates was significantly higher than those of the fiber mesh and hydrogel. Lamination significantly increased the extent of mineralization of BMS cells and laminates with HA and conjugated with RGD (Lam-RGD-HA) had 2.7-, 3.5- and 2.8-fold higher calcium content (compared to laminates without HA or RGD) after 7, 14 and 21days, respectively. The Lam-RGD-HA group had significantly higher expression of osteopontin and osteocalcin compared to the hydrogel or laminates without HA or RGD, consistent with the higher ALPase activity and calcium content of Lam-RGD-HA. Laminated osteon-mimetic structures have the potential to provide mechanical strength to the regenerating region as well as supporting the differentiation of progenitor cells to the osteogenic lineage.

Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1α from poly(lactide ethylene oxide fumarate) hydrogels

Stromal derived factor-1alpha (SDF-1alpha) is an important chemokine in stem cell trafficking and plays a critical role in the homing of bone marrow stromal (BMS) cells. However, its use in tissue regeneration is limited by its relatively short half-life and the time-dependent nature of cell homing to the site of injury. The objective of this work was to investigate the release characteristics of SDF-1alpha from degradable poly(lactide ethylene oxide fumarate) (PLEOF) hydrogels and to determine the effect of sustained release of SDF-1alpha on migration of BMS cells. Three PLEOF hydrogels with poly(l-lactide) (PLA) fractions of 6%, 9%, and 24% by weight were synthesized. After the addition of chemokine, the polymerizing mixture was crosslinked to produce SDF-1alpha loaded PLEOF hydrogels. The hydrogels were characterized with respect to sol fraction, water uptake, degradation, SDF-1alpha loading efficiency and release kinetics, and migration rate of bone marrow stromal (BMS) cells. The more hydrophilic hydrogels with 6% and 9% PLA fraction had a pronounced burst release followed by a period of sustained release by diffusion for 21 days. The more hydrophobic hydrogel with 24% PLA fraction had a less pronounced burst release and displayed a slow but constant release by diffusion between days 1 and 9 followed by a fast release by diffusion-degradation from days 9 to 18. The fraction of active SDF-1alpha released from 6%, 9%, and 24% hydrogels after 21 days was 34.3%, 32.3%, and 35.8%, respectively. The migration of BMS cells in response to time-released SDF-1alpha closely followed the protein release kinetics from the hydrogels. The biodegradable PLEOF hydrogel may potentially be useful as a delivery matrix for sustained release of SDF-1alpha in the proliferative phase of healing for recruitment of progenitor cells in tissue engineering applications.