Roya Ravarian

One-pot ATRP synthesis of a triple hydrophilic block copolymer with dual LCSTs and its thermo-induced association behavior

We report, for the first time, a facile one-pot ATRP synthesis of a triple hydrophilic block copolymer (THBC), PEG-b-PNIPAAm-b-P(NIPAAm-co-HEAAm), with dual LCSTs. The resulting THBCs exhibit a thermal-induced two-stage transition starting from unimers to micelles, and finally to vesicles upon increasing temperature.

Nanoscale Chemical Interaction Enhances the Physical Properties of Bioglass Composites

Bioglasses are favorable biomaterials for bone tissue engineering; however, their applications are limited due to their brittleness. In addition, the early failure in the interface is a common problem of composites of bioglass and a polymer with high mechanical strength. This effect is due to the phase separation, nonhomogeneous mixture, nonuniform mechanical strength, and different degradation properties of two compounds. To address these issues, in this study a nanoscale interaction between poly(methyl methacrylate) (PMMA) and bioactive glass was formed via silane coupling agent (3-trimethoxysilyl)propyl methacrylate (MPMA). A monolith was produced at optimum composition from this hybrid by the sol-gel method at 50 °C with a rapid gelation time (<50 min) that possessed superior physicochemical properties compared to pure bioglass and physical mixture. For instance, the Youngs modulus of bioglass was decreased 40-fold and the dissolution rate of silica was retarded 1.5-fold by integration of PMMA. Prolonged dissolution of silica fosters bone integration due to the continuous dissolution of bioactive silica. The primary osteoblast cells were well anchored and cell migration was observed on the surface of the hybrid. The in vivo studies in mice demonstrated that the integrity of the hybrids was maintained in subcutaneous implantation. They induced mainly a mononuclear phagocytic tissue reaction with a low level of inflammation, while bioglass provoked a tissue reaction with TRAP-positive multinucleated giant cells. These results demonstrated that the presence of a nanoscale interaction between bioglass and PMMA affects the properties of bioglass and broadens its potential applications for bone replacement.

Enhancing the biological activity of chitosan and controlling the degradation by nanoscale interaction with bioglass

A nonuniform degradation of physical mixture of organic-inorganic biomaterials increases their risk of failure. In this study a chemical bonding between chitosan and bioglass was used as an alternative product to address this issue. To prepare a homogenous composite, chitosan was functionalized with γ-glycidoxypropyl trimethoxysilane and chemically bonded with bioglass during sol-gel method. The gelation time of these hybrids samples was optimized by varying parameters such as composition of chitosan and temperature. It was shown that gelation time was reduced from 7 days for pure bioglass at 25°C to less than six minutes at 70°C for chitosan 40 vol % bioglass hybrid. Furthermore, the enzymatic degradation after 4 weeks was decreased from 80% mass loss for pure chitosan to 32% for chitosan 40 vol % bioglass hybrid. The results of in vitro study demonstrated that the presence of nanoscale interaction enhanced the bioactivity of chitosan. Additionally, hybrid scaffolds were fabricated with pore sizes in the range of 200-400 µm. These scaffolds were prepared by the addition of sodium bicarbonate during sol-gel method as a gas foaming agent and a neutralizer that resulted in decreasing the gelation time of hybrids to less than three minutes. The hybrids fabricated in this study possessed superior characteristics compared to chitosan, also physical mixture of chitosan-bioglass and are promising alternatives for bone tissue engineering applications.

Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering.

Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HAu2009>u2009micro-HAu2009>u2009TCPu2009>u2009BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering.

Development and characterization of a bioglass/chitosan composite as an injectable bone substitute

SiO2-CaO-P2O5 based bioglass (BG) systems constitute a group of materials that have wide applications in bone implants. Chitosan (Cn) is a biocompatible and osteoconductive natural polymer that can promote wound healing. In this study, bioactivity of chitosan/bioglass (CnB) composites as minimally invasive bone regenerative materials was assessed both in vitro and in vivo. Injectability tests and scanning electron microscopy (SEM) results demonstrated the formation of uniform injectable paste-like composites using BG particles and Cn. Fourier transform infrared spectroscopy (FTIR) and SEM images confirmed hydroxyapatite deposition in vitro after incubation in simulated body fluid (SBF). Higher BG content in the composite correlated with increased human osteoblast proliferation. An in vivo study in a rat spinal fusion model confirmed that increasing the amount of BG improved osteoconductivity. Manual palpation, radiographic images and pathological assessments proved that the composites promote bone formation. Based on these data, the synthesized composites have a potential application in orthopedic and reconstructive surgeries as a minimally invasive bone substitute.

Bioactive poly(methyl methacrylate) for bone fixation

Poly(methyl methacrylate) (PMMA) is broadly used for bone fixation. One of the major concerns of using this polymer is the lack of post-implantation integration with the host tissue. We have produced a novel hybrid ceramic–thermoplastic composite manufactured by a sol–gel method via covalent bonding between bioactive glass and PMMA to address this shortcoming. The uniform distribution of bioactive glass promoted the bioactivity of PMMA and substantially improved the biological properties. In this paper, we describe a refinement of the synthesis process of a previously manufactured PMMA–bioactive glass hybrid resulting in significantly more rapid fabrication. Key innovations were the replacement of tetrahydrofuran with ethanol as a more biologically benign reaction solvent, and the addition of sodium bicarbonate as a non-toxic catalyst. Our results showed that the gelation time was decreased 100-fold by increasing the reaction temperature from 25 °C to 70 °C, which also increased the rate of hardening 7-fold. The resulting hybrid monoliths displayed a more condensed structure with an 80% increase in network connectivity and 6-fold more resistance to degradation. These favorable biophysical properties of the new class of hybrids also enhanced the osteoblast adhesion and proliferation compared with the previously developed hybrids. This bioactive glass–PMMA hybrid has great potential to be used as a bone filler.

Improving the bioactivity of bioglass/ (PMMA-co-MPMA) organic/inorganic hybrid

Binary system of CaO-SiO2 glasses enables the apatite formation in simulated body fluid (SBF). However, the presence of phosphate content in SiO2-CaO-P2O5 glasses leads to the formation of orthophosphate nanocrystalline nuclei, which facilitates the generation of carbonate hydroxyapatite; this compound is more compatible with natural bone. The brittle and less flexible properties of bioactive glasses are the major obstacle for their application as bone implant. The hybridization of essential constituents of bioactive glasses and glass-ceramics with polymers such as PMMA can improve their poor mechanical properties. The aim of this study was to improve the bioactivity of nanocomposites fabricated from poly(methyl metacrylate) (PMMA) and bioglass for bone implant applications. Bioglass compounds with various phosphate contents were used for the preparation of PMMA/bioglass hybrid matrices. Since the lack of adhesion between the two phases impedes the homogenous composite formation, a silane coupling agent such as 3-(trimethoxysilyl)propyl methacrylates (MPMA) was incorporated into the polymer structure. The effect of addition of MPMA on the molecular structure of composite was investigated. Furthermore, the presence of MPMA in the system improved the homogeneity of sample. Increasing phosphate content in the inorganic segment of hybrid up to 10 mol% resulted in the formation of apatite layer on the surface; hence the hybrid was bioactive and suitable candidate for bone tissue engineering.

Fabrication of interpenetrate chitosan: Bioactive glass, using dense gas CO 2

Success of bone tissue engineering relies on using bioactive scaffolds with ideal pore morphology which can mimic the properties of the natural extracellular matrix (ECM). The objective of this study was to interpenetrate bioactive glass components throughout the three dimensional (3D) structure of the chitosan scaffold to increase the average pore size of the scaffold and also the osteoconductivity and osteoinductivity of the fabricated scaffold. Scanning electron microscopy was used to observe the microsturcture of the hydrogel. The results of this study demonstrated that the average pore size in the hydrogel was increased significantly (p<0.05) from 97±44μm to 150±24μm by increasing the BG concentration from 0 wt% to 40 wt%. This effect might be due to the interaction between ceramic and chitosan. The composite hydrogel fabricated swell in water and has high potential to be used for bone tissue engineering applications; bioactive glass can substantially improve bioactivity of the bone tissue engineering scaffolds However, further studies are required to investigate the effect of BG on the biocompatibility of the scaffolds. In addition, in vitro cell studies are also required to confirm the suitability of the fabricated scaffold for bone tissue engineering.