Localized delivery and enhanced osteogenic differentiation with biodegradable galactitol polyester elastomers

Given that a large fraction of the population suffers from orthopaedic diseases, the research in developing polymeric biomaterials for bone tissue regeneration applications is witnessing an exponential growth rate. We present a spectrum of novel polyesters synthesized by the reaction of galactitol with dicarboxylic acids, namely adipic acid, suberic acid and dodecanedioic acid. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy confirmed the chemical structure of the polymers. Thermal characterization revealed that these polyesters were semi-crystalline. The molecular weight of the polyesters showed an increase with increase in the chain length of the diacid and the molar ratio of galactitol : diacid. Dynamic mechanical analysis showed that the polymers were elastomeric in nature with the increase in chain length and molar ratio of galactitol : diacids. Surface hydrophobicity and the swelling ratio increase with increase in the chain length and molar ratio of galactitol : diacids. Hydrolytic degradation studies demonstrated that the kinetics of the degradation followed first order. Dye release studies indicated that the rate of release followed Higuchi kinetics. In vitro studies confirmed the cytocompatible nature of these polymers. Mineralization by osteoblasts in vitro suggests that these polymers support osteogenic differentiation, thus elucidating that these polymers are promising candidate materials for bone tissue engineering. Thus, this study presents a significant advance in which the mechanical properties, degradation and release rates of the polyesters may be tuned by manipulating the process parameters

Tailoring the degradation rate and release kinetics from poly(galactitol sebacate) by blending with chitosan, alginate or ethyl cellulose

Despite significant advances in recent times, the investigation of discovering a perfect biomaterial is perennial. In this backdrop, blending of natural and synthetic polymers is gaining popularity since it is the easiest way to complement the drawbacks and attain a superlative material. Based on this, the objective of this study was to synthesize a novel polyester, poly(galactitol sebacate), and subsequently blend this polymer with one of the three natural polymers such as alginate, chitosan or ethyl cellulose. FT-IR showed the presence of both the polymers in the blends. H-1 NMR confirmed the chemical structure of the synthesized poly (galactitol sebacate). Thermal characterization was performed by DSC revealing that the polymers were amorphous in nature and the glass transition temperatures increased with the increase in ratio of the natural polymers in the blends. SEM imaging showed that the blends were predominantly homogeneous. Contact angle measurements demonstrated that the blending imparted the hydrophilic nature into poly (galactitol sebacate) when blending with alginate or chitosan and hydrophobic when blending with ethyl cellulose. In vitro hydrolytic degradation studies and dye release studies indicated that the polymers became more hydrophilic in alginate and chitosan blends and thus accelerated the degradation and release process. The reverse trend was observed in the case of ethyl cellulose blends. Modeling elucidated that the degradation and dye release followed first order kinetics and Higuchi kinetics, respectively. In vitro cell studies confirmed the cytocompatible nature of the blends. It can be proposed that the chosen natural polymers for blending showed wide variations in hydrophilicity resulting in tailored degradation, release and cytocompatibility properties and thus are promising candidates for use in drug delivery and tissue engineering. (C) 2016 Elsevier B.V. All rights reserved

Maltitol-based biodegradable polyesters with tailored degradation and controlled release for bone regeneration

Despite extensive research performed in the area of drug delivery and tissue engineering, the search for a perfect biomaterial remains an ongoing process. In an effort to find this material, novel maltitol-based polyesters using three different dicarboxylic acids (DCAs; adipic acid, dodecanedioic acid and suberic acid) were synthesized and their properties were investigated. The chemical structure of the polymers was confirmed using Fourier transform infrared and proton nuclear magnetic resonance spectroscopies. Thermal characterization revealed that the polymers were amorphous and that the glass transition temperature decreased with an increase in the chain length and molar ratio of maltitol : DCAs. Mechanical studies showed that the moduli of these polymers were comparable to those of the components of the skeletal system. Contact angle goniometry confirmed that the hydrophobicity of the polymers increased with increase in chain length and the molar ratio of maltitol : DCAs. The polymer degradation followed first order kinetics whereas dye release from these polymers followed zero order kinetics. Both the degradation and dye release studies demonstrated that the degradation and release decreased with increase in chain length and molar ratio of maltitol : DCA. The degradation and dye release can be modulated based on the chain length and the molar ratio of acids. Preliminary cytocompatibility studies showed that these polymers were cytocompatible. Mineralization studies revealed that these polymers showed increased mineralization when compared to results obtained with controls. Thus, this family of polyesters can serve as effective biomaterials for bone tissue engineering with tunable degradation and controlled release properties

Biodegradable galactitol based crosslinked polyesters for controlled release and bone tissue engineering

Various classes of biodegradable polymers have been explored towards finding alternates for the existing treatments for bone disorders. In this framework, two families of polyesters using an array of crosslinkers were synthesized. One was based on galactiol/adipic acid and the other based on galactitol/dodecanedioic acid. The structures of the polymers were confirmed by FTIR and further confirmed by H-1 NMR. DSC showed that the polymers were amorphous and the glass transition temperature increased with increase in crosslinking. DMA and contact angle analysis revealed that the modulus and hydrophobicity increased with increase in crosslinking. Swelling studies demonstrated that %swelling decreased with increase in crosslinlcing. The in vitro hydrolytic degradation studies and dye release studies of all the polymers exhibited that the degradation and release rate decreased with increase in crosslinking, hydrophobicity and modulus. Degradation and release followed first order kinetics and Higuchi kinetics, respectively. The preliminary in vitro cytotoxicity studies proved that this array of polymers was not cytotoxic. Osteogenic differentiation of pre-osteoblasts was observed in three dimensional (3D) porous scaffolds prepared using these polymers. This study demonstrates the ability to modulate the physical properties, degradation and release kinetics of these biodegradable polymers through smart selection of crosslinkers. The findings of these studies have important implications for developing novel biodegradable polymers for drug delivery and tissue engineering applications. (C) 2017 Elsevier B.V.All rights reserved

Poly(ester amide)s from Poly(ethylene terephthalate) Waste for Enhancing Bone Regeneration and Controlled Release

The present study elucidates the facile synthesis and exceptional properties of a family of novel poly­(ester amide)­s (PEAs) based on bis­(2-hydroxy ethylene) terephthalamide that was obtained from the poly­(ethylene terephthalate) waste. Fourier transform infrared and ¹H NMR were used to verify the presence of ester and amide in the polymer backbone. Differential scanning calorimetry data showed that the glass transition temperature decreased with as the chain length of dicarboxylic acids increased. Dynamic mechanical analysis and contact angle studies proved that the modulus values and hydrophobicity increased with as the chain lengths of dicarboxylic acids increased. <i>In vitro</i> hydrolytic degradation and dye release studies demonstrated that the degradation and release decreased with as the chain lengths of dicarboxylic acids increased. Modeling these data illustrated that degradation and release follow first-order degradation and zero-order release, respectively. The <i>in vitro</i> cytocompatibility studies confirmed the minimal toxicity characteristic of these polymers. Osteogenic studies proved that these polymers can be highly influential in diverting the cells toward osteogenic lineage. Alizarin red staining evinced the presence of twice the amount of calcium phosphate deposits by the cells on these polymers when compared to the control. The observed result was also corroborated by the increased expression of alkaline phosphatase. These findings were further validated by the markedly higher mRNA expressions for known osteogenic markers using real time polymerase chain reaction. Therefore, these polymers efficiently promoted osteogenesis. This study demonstrates that the physical properties, degradation, and release kinetics can be altered to meet the specific requirements in organ regeneration as well as facilitate simultaneous polymer resorption through control of the chain length of the monomers. The findings of this study have significant implications for designing cost-effective biodegradable polymers for tissue engineering

Polyanhydrides of Castor Oil-Sebacic Acid for Controlled Release Applications

A family of high molecular weight castor oil (CO)-based biodegradable polyanhydrides was synthesized by a catalyst-free melt-condensation reaction between prepolymers of CO and sebacic acid (SA). The structure of the polymers was characterized by H-1 NMR and Fourier transform infrared spectroscopy, which indicated the formation of the anhydride bond along the polymer backbone. Thermal analysis and X-ray diffraction confirmed the semicrystalline nature of the polymers. Incorporation of SA enhanced the crystallinity of the polymer. The hydrophobic nature of these polymers was revealed by contact angle goniometry. Water wettability decreased with increase in SA content. Compressive tests demonstrated a sharp increase in strength and decrease in ductility with increasing SA content. In vitro hydrolytic degradation studies indicated surface-eroding behavior. The degradation rate decreased with an increase of SA content in the polymers because of increased crystallinity. The release studies of both hydrophobic and hydrophilic dyes followed zero-order kinetics. In vitro cell studies to assess the cytotoxicity of the polymer confirmed minimal toxicity of the degradation products. Thus, a family of CO-SA polyanhydrides have been synthesized and characterized for controlled release applications where the physical, mechanical, and degradation kinetics can be modulated by varying the weight fraction of the prepolymers

Polyanhydrides of Castor Oil–Sebacic Acid for Controlled Release Applications

A family of high molecular weight castor oil (CO)-based biodegradable polyanhydrides was synthesized by a catalyst-free melt–condensation reaction between prepolymers of CO and sebacic acid (SA). The structure of the polymers was characterized by ¹H NMR and Fourier transform infrared spectroscopy, which indicated the formation of the anhydride bond along the polymer backbone. Thermal analysis and X-ray diffraction confirmed the semicrystalline nature of the polymers. Incorporation of SA enhanced the crystallinity of the polymer. The hydrophobic nature of these polymers was revealed by contact angle goniometry. Water wettability decreased with increase in SA content. Compressive tests demonstrated a sharp increase in strength and decrease in ductility with increasing SA content. In vitro hydrolytic degradation studies indicated surface-eroding behavior. The degradation rate decreased with an increase of SA content in the polymers because of increased crystallinity. The release studies of both hydrophobic and hydrophilic dyes followed zero-order kinetics. In vitro cell studies to assess the cytotoxicity of the polymer confirmed minimal toxicity of the degradation products. Thus, a family of CO-SA polyanhydrides have been synthesized and characterized for controlled release applications where the physical, mechanical, and degradation kinetics can be modulated by varying the weight fraction of the prepolymers