Covalently Crosslinked Organic/Inorganic Hybrid Biomaterials for Bone Tissue Engineering Applications

Scaffolds are key components for bone tissue engineering and regeneration. They guide new bone formation by mimicking bone extracellular matrix for cell recruitment and proliferation. Ideally, scaffolds for bone tissue engineering need to be osteoconductive, osteoinductive, porous, degradable and mechanically competent. As a single material can not provide all these requirements, composites of several biomaterials are viable solutions to combine various properties. However, conventional composites fail to fulfil these requirements due to their distinct phases at the microscopic level. Organic/inorganic (O/I) class II hybrid biomaterials, where the organic and inorganic phases are chemically crosslinked on a molecular scale, hence the phases are homogenously dispersed, are the ideal choices for bone tissue engineering. In this research, polycaprolactone/borophosphosilicate glass (PCL/BPSG) and poly(vinylpyrrolidone-co-triethoxyvinylsilane)/bioactive glass (Poly(VP-co-TEVS)/BG) class II hybrid biomaterials were successfully prepared via a sol-gel process. PCL was functionalized with 3-glycidoxypropyl trimethoxysilane at both ends prior to hybrid syntheses. Trimethoxysilane-functionalized PCL was then polycondensed with the glass precursors via non-aqueous sol gel reactions to form covalently bonded O/I network with -C-Si-O-Si- bonds. The resultant amorphous and transparent hybrid materials exhibited apatite depositions when incubated with simulated body fluid. The ultimate compressive stress, modulus and toughness of these hybrids were significantly greater compared with their conventional composites counterparts, attributed to the covalent bonding between the O/I phases. In addition, these hybrids exhibited more controlled degradation and subsequent ion release without showing any abrupt features. Pre-osteoblast cells seeded on the hybrid biomaterials displayed enhanced spreading, focal adhesion formation, and cell number, indicating cytocompatibility. PCL/BPSG hybrid scaffolds were prepared by a solvent-free casting and particulate leaching methods to obtain consistent pore size distribution, controllable porosity and pore interconnectivity. Significant number of cell infiltration and adhesion into the scaffolds were observed in cell culture conditions. Bone-associated gene expression by induced pluripotent stem cells on these scaffolds revealed that the hybrid scaffolds had an upregulating effect on gene expressions for alkaline phosphatase, osteopontin and osteocalcin

Sol-gel derived tertiary bioactive glass–ceramic nanorods prepared via hydrothermal process and their composites with poly(Vinylpyrrolidone-Co-Vinylsilane)

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Bioactive glass (BG) nanoparticles have wide applications in bone repair due to their bone-bonding and biodegradable nature. In this work, nanometric rod-shaped ternary SiO2-CaO-P2O5 bioactive glass particles were prepared through sol-gel chemistry followed by a base-induced hydrothermal process at 130 ◦C and 170 ◦C for various times up to 36 h. This facile, low-temperature and surfactant-free hydrothermal process has shown to be capable of producing uniform nanorods and nanowires. One-dimensional growth of nanorods and the characteristics of siloxane bridging networks were dependent on the hydrothermal temperature and time. Hardened bioactive composites were prepared from BG nanorods and cryo-milled poly(vinylpyrrolidone-co-triethoxyvinylsilane) in the presence of ammonium phosphate as potential bone graft biomaterials. Covalent crosslinking has been observed between the organic and inorganic components within these composites. The ultimate compressive strength and modulus values increased with increasing co-polymer content, reaching 27 MPa and 500 MPa respectively with 30% co-polymer incorporation. The materials degraded in a controlled non-linear manner when incubated in phosphate-buffered saline from 6 h to 14 days. Fibroblast cell attachment and spreading on the composite were not as good as the positive control surfaces and suggested that they may require protein coating in order to promote favorable cell interactions

Bone repair and regenerative biomaterials: Towards recapitulating the microenvironment

© 2019 by the authors. Biomaterials and tissue engineering scaffolds play a central role to repair bone defects. Although ceramic derivatives have been historically used to repair bone, hybrid materials have emerged as viable alternatives. The rationale for hybrid bone biomaterials is to recapitulate the native bone composition to which these materials are intended to replace. In addition to the mechanical and dimensional stability, bone repair scaffolds are needed to provide suitable microenvironments for cells. Therefore, scaffolds serve more than a mere structural template suggesting a need for better and interactive biomaterials. In this review article, we aim to provide a summary of the current materials used in bone tissue engineering. Due to the ever-increasing scientific publications on this topic, this review cannot be exhaustive; however, we attempted to provide readers with the latest advance without being redundant. Furthermore, every attempt is made to ensure that seminal works and significant research findings are included, with minimal bias. After a concise review of crystalline calcium phosphates and non-crystalline bioactive glasses, the remaining sections of the manuscript are focused on organic-inorganic hybrid materials

Scattering of Fexural Gravity Waves by a Two-Dimensional Thin Plate

An approximate analysis based on standard perturbation technique together with an application of Green’s integral theorem is used in this paper to study the problem of scattering of water waves by a two dimensional thin plate submerged in deep ocean with ice cover. The reflection and transmission coefficients upto first order are obtained in terms of the shape function describing the plate and are studied graphically for different shapes of the plate

Length-weight relationship, condition factor and gonado-somatic index of Labeo calbasu (Hamilton, 1822)

An attempt was made to study dynamics of length-weight relationship (LWR), relative condition factor (Kn) and gonado-somatic index (GSI) of Labeo calbasu from the wetlands of South 24 Parganas district of West Bengal, India. A total of 275 fish specimens (130 to 430 mm) were examined over nine months from December 2006 to August 2007. Specimens were categorized into two groups based on the size at first maturity of 260 mm.  The LWR was recorded W = 0.007269 L3.181 for Group A (<260 mm) and W = 0.007367 L3.031 for Group B (≥260 mm). The individuals exhibited isometric growth. The monthly mean Kn values varied from 0.924 to 1.141 with an average value of 1.059. The mean monthly values of GSI varied from 0.544 to 3.301 for male and 0.560 to 9.649 for female. There was significant variation (P < 0.05) in the mean values of GSI in different months between sexes

mSLA-based 3D printing of acrylated epoxidized soybean oil - nano-hydroxyapatite composites for bone repair

Structural bone allografts are used to treat critically sized segmental bone defects (CSBDs) as such defects are too large to heal naturally. Development of biomaterials with competent mechanical properties that can also facilitate new bone formation is a major challenge for CSBD repair. 3D printed synthetic bone grafts are a possible alternative to structural allografts if engineered to provide appropriate structure with sufficient mechanical properties. In this work, we fabricated a set of novel nanocomposite biomaterials consisting of acrylated epoxidized soybean oil (AESO), polyethylene glycol diacrylate (PEGDA) and nanohydroxyapatite (nHA) by using masked stereolithography (mSLA)-based 3D printing. The nanocomposite inks possess suitable rheological properties and good printability to print complex, anatomically-precise, ‘by design’ grafts. The addition of nHA to the AESO/PEGDA resin improved the tensile strength and fracture toughness of the mSLA printed nanocomposites, presumably due to small-scale reinforcement. By adding 10 vol% nHA, tensile strength, modulus and fracture toughness (KIc) were increased to 30.8 ± 1.2 MPa (58% increase), 1984.4 ± 126.7 MPa (144% increase) and 0.6 ± 0.1 MPa·m1/2 (42% increase), respectively (relative to the pure resin). The nanocomposites did not demonstrate significant hydrolytic, enzymatic or oxidative degradation when incubated for 28 days, assuring chemical and mechanical stability at early stages of implantation. Apatite nucleated and covered the nanocomposite surfaces within 7 days of incubation in simulated body fluid. Good viability and proliferation of differentiated MC3T3-E1 osteoblasts were also observed on the nanocomposites. Taken all together, our nanocomposites demonstrate excellent bone-bioactivity and potential for bone defect repair.Canadian Institutes of Health Research || Canada Foundation for Innovation || Ontario Research Fund || University of Waterloo's Engineering Research Initiatives || Natural Sciences & Engineering Research Counci

Sol-Gel Derived Tertiary Bioactive Glass–Ceramic Nanorods Prepared via Hydrothermal Process and Their Composites with Poly(Vinylpyrrolidone-Co-Vinylsilane)

Bioactive glass (BG) nanoparticles have wide applications in bone repair due to their bone-bonding and biodegradable nature. In this work, nanometric rod-shaped ternary SiO2-CaO-P2O5 bioactive glass particles were prepared through sol-gel chemistry followed by a base-induced hydrothermal process at 130 °C and 170 °C for various times up to 36 h. This facile, low-temperature and surfactant-free hydrothermal process has shown to be capable of producing uniform nanorods and nanowires. One-dimensional growth of nanorods and the characteristics of siloxane bridging networks were dependent on the hydrothermal temperature and time. Hardened bioactive composites were prepared from BG nanorods and cryo-milled poly(vinylpyrrolidone-co-triethoxyvinylsilane) in the presence of ammonium phosphate as potential bone graft biomaterials. Covalent crosslinking has been observed between the organic and inorganic components within these composites. The ultimate compressive strength and modulus values increased with increasing co-polymer content, reaching 27 MPa and 500 MPa respectively with 30% co-polymer incorporation. The materials degraded in a controlled non-linear manner when incubated in phosphate-buffered saline from 6 h to 14 days. Fibroblast cell attachment and spreading on the composite were not as good as the positive control surfaces and suggested that they may require protein coating in order to promote favorable cell interactions

Bioactive borophosphosilicate-polycaprolactone hybrid biomaterials: Via a non-aqueous sol gel process

© 2016 The Royal Society of Chemistry. In this study, a non-aqueous sol-gel process was utilized to prepare novel class II hybrid biomaterials based on functionalized polycaprolactone (PCL) diol and borophosphosilicate glass (BPSG) as potential scaffold material for bone tissue engineering applications. PCL diol was first functionalized by reacting with (3-glycidoxypropyl)trimethoxysilane. The functionalized PCL (PCL-Si) was condensed with trimethyl borate, tetraethyl orthosilicate and triethyl phosphate via non-aqueous sol-gel reactions to form covalently bonded organic-inorganic networks. FTIR, TGA, XRD, and solid state 29Si CP-MAS NMR analyses revealed that the hybrid materials were successfully prepared. Furthermore, the hybrids were amorphous and transparent up to 60 wt% of PCL-Si content. Specifically, the organic-inorganic networks had a dominant T3 network since Si-C bond from PCL-Si is covalently bonded with the inorganic glass network and resulted in a class II hybrid. EDX and XPS studies showed uniform distribution of the various elements making up the hybrid materials. When incubated with simulated body fluids (SBF), the present hybrid materials were able to stimulate the deposition of crystalline hydroxyapatite. This study demonstrated, for the first time, the chemical reactivity of calcium-free BPSG and PCL-BPSG hybrids and their ability to deposit hydroxyapatite when incubated in SBF. The present study is also the first to incorporate B2O3 as a glass component in class II organic-inorganic hybrid biomaterials

Porous and biodegradable polycaprolactone-borophosphosilicate hybrid scaffolds for osteoblast infiltration and stem cell differentiation

© 2019 Elsevier Ltd The composition and microstructure of bone tissue engineering scaffolds play a significant role in regulating cell infiltration, proliferation, differentiation, and extracellular matrix production. While boron is an essential trace element for bone formation, growth, and health, boron-containing biomaterials are poorly studied. Specifically, the effect of boron in hybrid scaffolds on stem cell differentiation is unknown. We have previously reported the synthesis and characterization of class II hybrid biomaterials from polycaprolactone and borophosphosilicate glass (PCL/BPSG). In this study, PCL/BPSG hybrid porous scaffolds were fabricated by a solvent-free casting and particulate leaching method having consistent pore-size distribution, controlled porosity, and pore interconnectivity. The mechanical properties with respect to porogen loading and degradation time demonstrated that these scaffolds were competent for bone tissue engineering applications. In cell culture experiments, significant number of cells infiltrated and adhered into the scaffolds interior. Induced pluripotent stem cells (iPSCs) differentiation to osteogenic lineage was dependent on the amount of boron incorporated into the hybrid scaffolds. Consistent with this, scaffolds containing 2-mol% boron (calculated as % of the inorganic component) had an optimum effect on lineage expressions for alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN). These results suggest that PCL/BPSG hybrid scaffolds with optimum-level boron may enhance bone formation

Bioactivity, Degradation, and Mechanical Properties of Poly(vinylpyrrolidone-co-triethoxyvinylsilane)/Tertiary Bioactive Glass Hybrids

Copyright © 2018 American Chemical Society. Currently, composite and class I hybrid biomaterials are used for tissue regeneration applications. To improve and better control biomaterial properties, we synthesized class II organic/inorganic (O/I) hybrids, in which organic polymers and inorganic tertiary bioactive glass (TBG) were covalently cross-linked. To tailor their microstructure, bioactivity, degradation, and mechanical properties, we altered the degree of cross-linking by varying the amount of functional groups in the polymer that mediate covalent bonding to the TBG. We synthesized class II hybrids in a two-step process: First, vinylpyrrolidone (VP) and triethoxyvinylsilane (TEVS) were copolymerized at various molar ratios to obtain different amounts of silane functional groups in the copolymer; second, TBG and the copolymer were mixed and allowed to undergo hydrolysis and polycondensation forming Si-O-Si- A nd Si-O-P-bridging networks between the organic and inorganic phases. Higher amounts of functional groups increased copolymer-TBG covalent bonding and decreased degradation and the release of TBG dissolution products. Incubation in simulated body fluid led to biomimetic apatite deposition on the hybrid biomaterial surfaces, which was primarily dependent on O/I weight ratios. A higher TBG content improved apatite deposition and biocompatibility. Porous and interconnected three-dimensional scaffolds, fabricated by indirect 3D printing using polycaprolactone as a sacrificial template, had intriguing yield and compressive strengths, compressive moduli, and toughness. These studies demonstrate, for the first time, that the functionality of our synthesized copolymers greatly affects the nature of O/I matrix formation and degradation behavior of the class II hybrid biomaterials, creating possibilities for tailoring the physical, biochemical, and mechanical properties of scaffold biomaterials for tissue regeneration and related applications