Anurima Singh

Mechanical properties and osteocompatibility of novel biodegradable alanine based polyphosphazenes: Side group effects

The versatility of polymers for tissue regeneration lies in the feasibility to modulate the physical and biological properties by varying the side groups grafted to the polymers. Biodegradable polyphosphazenes are high-molecular-weight polymers with alternating nitrogen and phosphorus atoms in the backbone. This study is the first of its kind to systematically investigate the effect of side group structure on the compressive strength of novel biodegradable polyphosphazene based polymers as potential materials for tissue regeneration. The alanine polyphosphazene based polymers, poly(bis(ethyl alanato) phosphazene) (PNEA), poly((50% ethyl alanato) (50% methyl phenoxy) phosphazene) (PNEA(50)mPh(50)), poly((50% ethyl alanato) (50% phenyl phenoxy) phosphazene) (PNEA(50)PhPh(50)) were investigated to demonstrate their mechanical properties and osteocompatibility. Results of mechanical testing studies demonstrated that the nature and the ratio of the pendent groups attached to the polymer backbone play a significant role in determining the mechanical properties of the resulting polymer. The compressive strength of PNEA(50)PhPh(50) was significantly higher than poly(lactide-co-glycolide) (85:15 PLAGA) (p<0.05). Additional studies evaluated the cellular response and gene expression of primary rat osteoblast cells on PNEA, PNEA(50)mPh(50) and PNEA(50)PhPh(50) films as candidates for bone tissue engineering applications. Results of the in vitro osteocompatibility evaluation demonstrated that cells adhere, proliferate, and maintain their phenotype when seeded directly on the surface of PNEA, PNEA(50)mPh(50), and PNEA(50)PhPh(50). Moreover, cells on the surface of the polymers expressed type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein, which are characteristic genes for osteoblast maturation, differentiation, and mineralization.

Development and Characterization of Biodegradable Nanocomposite Injectables for Orthopaedic Applications Based on Polyphosphazenes

Self-setting hydroxyapatite–biodegradable injectable composites are excellent candidates for applications in orthopaedics. We have previously demonstrated the feasibility of development of self-setting calcium-deficient nanocrystalline hydroxyapatite–polymer composites using different calcium phosphate precursors and biodegradable polyphosphazenes. This study aimed to evaluate these novel injectable composites as suitable materials for orthopaedic applications through evaluating their biomechanical properties, osteoblast cellular attachment and gene expression over time.Our studies demonstrated that the morphology of the composite groups (PNEA–CDHA, PNEA–CDSHA, PNEA50mPh50–CDHA, PNEA50mPh50–CDSHA, PNEA50PhPh50–CDHA, and PNEA50PhPh50–CDSHA) formed was similar and found to have micro- and nanoporous structures resembling trabecular bone. The osteoblast phenotypic marker of bone, alkaline phosphatase, was expressed by the cells on the surface of the composites throughout the study and was comparable to tissue-culture polystyrene (control). Furthermore, the cells seeded on the composites expressed the characteristic osteoblastic genes, such as type-I collagen, alkaline phosphatase, osteocalcin, osteopontin and bone sialoprotein, indicating osteoblast differentiation, maturation and mineralization. Within our injectable composite groups, significant gene expression levels were displayed (P < 0.05). These novel injectable biodegradable polyphosphazenes–calcium-deficient hydroxyapatites materials are promising candidates for orthopaedic applications.

Hydrophobic and Superhydrophobic Polyphosphazenes

Polyphosphazenes are a class of hybrid organic–inorganic polymers that have good solubility in classical organic solvents and are thermo-oxidatively stable. Over the years, poly(dichlorophosphazene) has been used as a macromolecular intermediate to yield a number of polymers which can be hydrophobic or superhydrophobic. This review deals with several classical hydrophobic polyphosphazenes such as poly(bis-2,2,2-trifluoroethoxyphosphazene), species with siloxane containing substituents and phosphazene graft polymers. Poly(phosphazophosphazenes) and phenoxy-substituted polyphosphazenes are some of the more recent polymers that have been examined for their hydrophobic character. Processing methods such as electrospinning can enhance the hydrophobicity of polyphosphazenes to move them into the realm of superhydrophobic materials. Many polymers which are only borderline hydrophobic can now be converted into superhydrophobic materials by the use of environmental plasma treatment.

Development of Biodegradable Polyphosphazene- Nanohydroxyapatite Composite Nanofibers Via Electrospinning

Abstract : Biodegradable polymeric nanofibers are of great interest as scaffolds for tissue engineering and drug delivery due to their extremely high surface area, high aspect ratio and similarity in structure to the extracellular matrix (ECM). Polyphosphazenes due to their synthetic flexibility, wide range of physico-chemical properties, non-toxic and neutral degradation products and excellent biocompatibility are suitable candidates for biomedical applications. The objective of the present study was to develop and evaluate composite nanofibers of a biodegradable polyphosphazene, polyBIS(ETHYL ALANATO)PHOSPHAZENE (PNEA) and nanocrystals of hydroxyapatite (nHAp) via electrospinning. A suspension of nHAp in dimethyl formamide (DMF) sonicated with PNEA solution in tetrahydrofuran (THF) was used to develop composite nanofiber matrices via electrospinning at ambient conditions. In the present study the theoretical loading of nHAp was varied from 50%-90% (w/w) to PNEA. The nHAp content (actual loading of nHAp) of the composite nanofibers was determined by gravimetric estimation. The composite nanofibers were characterized by transmission electron microscopy (TEM), gravimetry and energy dispersive X-ray mapping. This study demonstrated the feasibility of developing novel composite nanofibers of biodegradable polyphosphazenes with more than 50% (w/w) loading of nHAp on and within the nanofibers.

Development of Novel Biodegradable Amino Acid Ester Based Polyphosphazene– Hydroxyapatite Composites for Bone Tissue Engineering

Abstract : Hydroxyapatite formed from low temperature setting calcium phosphate cements (CPC) are currently been used for various orthopaedic applications. CPCs are attractive candidates for the development of scaffolds for bone tissue engineering, since they are moldable, resorbable, set at physiological temperature without the use of toxic chemicals, and can be processed in an operating room setting. However they may have mechanical disadvantages which seriously limit them to non-load bearing orthopaedic applications, The aim of the present study was to develop composites from ployphosphazenes and calcium deficient hydroxyapatite precursors to form poorly crystalline hydroxyapatite-polymer composites. Composites were formed from calcium deficient hydroxyapatite precursors (Ca/P - 1.5, 1.6) and biodegradable polyphosphazenes, polyBIS(ETHYL ALANATO)PHOSPHAZENE (PNEA50mPh50) at physiological temperature. The results demonstrated that poorly crystalline hydroxyapatite that resembled the mineral component of bone was formed in the presence of biodegradable polyphosphazenes. The surface morphology of all the four composites was identical with a porous microstructure. The composites supported the adhesion and proliferation of osteoblast like MC3T3-E1 cells making them potential candidates for bone tissue engineering.