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Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly-lactic acid co-epsilon-caprolactone (PLA-CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically-unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. The matrix obtained from the highest polymeric-film casting concentration showed a controlled release of model biologics payload. The tested matrices rapidly degraded during the initial 4 weeks due to preferential hydrolysis of the lactide-rich regions within the polymer, and subsequently maintained a stable molecular weight due to the emergence of highly-crystalline caprolactone-rich regions. pH evaluation in the interior of the matrix showed minimal change signifying lesser accumulation of acidic degradation byproducts than seen in other bulk-degrading polymers, and maintenance of conformational stability of the model biologic payload. The context-dependent biocompatibility evaluation in a rodent model of acute rotator cuff repair showed matrix remodeling without eliciting excessive inflammatory reaction and is anticipated to completely degrade within 6 months. The engineered PLA-CL matrices offer unique advantages in controlled and protected biologic delivery, non-toxic biodegradation, and biocompatibility overcoming several limitations of commonly-used biodegradable polyesters.

A biocompatible and biodegradable scaffold with load-bearing ability is required to enhance the repair of bone defects by facilitating the attachment, and proliferation of cells, and vascularization during new bone formation. However, it is challenging to maintain the porosity and biodegradability, as well as mechanical properties (especially compressive strength), at the same time. Therefore, in the present work, a biodegradable composite structure of poly(caprolactone) (PCL) was designed using compression molding with varying amounts of poly(glycolic acid) (PGA) (25, 50, 75 wt%) and fixed amount (20 wt%) of beta tricalcium phosphate (beta TCP). It was hypothesized that the fabricated composite structure will develop porosity during the degradation of the PGA and that the corresponding decrease in mechanical properties will be compensated by new bone formation and ingrowth, in vivo. Accordingly, we have systematically studied the effects of sample composition on time-dependent dissolution and mechanical properties of the PGA/beta TCP scaffolds. The compressive strength increased up to ~92 MPa at 50% compression of the designed PCL-PGA samples. Furthermore, the dissolution rate, as well as weight loss, was observed to increase with an increase in the PGA amount in PCL. Based on the mechanical properties and dissolution data, it is concluded that the PCL-PGA scaffolds with beta TCP can be suitable candidates for bone tissue engineering applications, specifically for the reconstruction of bone defects, where strength and biodegradation are both important characteristics.

In this paper, we report on a novel biocompatible micromechanical bioreactor (actuator and sensor) designed for the in situ manipulation and characterization of live microtissues. The purpose of this study was to develop and validate an application-targeted sterile bioreactor that is accessible, inexpensive, adjustable, and easily fabricated. Our method relies on a simple polydimethylsiloxane (PDMS) molding technique for fabrication and is compatible with commonly-used laboratory equipment and materials. Our unique design includes a flexible thin membrane that allows for the transfer of an external actuation into the PDMS beam-based actuator and sensor placed inside a conventional 35 mm cell culture Petri dish. Through computational analysis followed by experimental testing, we demonstrated its functionality, accuracy, sensitivity, and tunable operating range. Through time-course testing, the actuator delivered strains of over 20% to biodegradable electrospun poly (D, L-lactide-co-glycolide) (PLGA) 85:15 non-aligned nanofibers (~91 &micro, m thick). At the same time, the sensor was able to characterize time-course changes in Young&rsquo, s modulus (down to 10&ndash, 150 kPa), induced by an application of isopropyl alcohol (IPA). Furthermore, the actuator delivered strains of up to 4% to PDMS monolayers (~30 &micro, m thick), simultaneously characterizing their elastic modulus up to ~2.2 MPa. The platform repeatedly applied dynamic (0.23 Hz) tensile stimuli to live Human Dermal Fibroblast (HDF) cells for 12 hours (h) and recorded the cellular reorientation towards two angle regimes, with averages of &minus, 58.85&deg, and +56.02&deg, The device biocompatibility with live cells was demonstrated for one week, with no signs of cytotoxicity. We can conclude that our PDMS bioreactor is advantageous for low-cost tissue/cell culture micromanipulation studies involving mechanical actuation and characterization. Our device eliminates the need for an expensive experimental setup for cell micromanipulation, increasing the ease of live-cell manipulation studies by providing an affordable way of conducting high-throughput experiments without the need to open the Petri dish, reducing manual handling, cross-contamination, supplies, and costs. The device design, material, and methods allow the user to define the operational range based on their targeted samples/application.

A biodegradable scaffold with tissue ingrowth and load-bearing capabilities is required to accelerate the healing of bone defects. However, it is difficult to maintain the mechanical properties as well as biodegradability and porosity (necessary for bone ingrowth) at the same time. Therefore, in the present study, polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA5050) were mixed in varying ratio and incorporated with 20 wt.% βTCP. The mixture was shaped under pressure into originally non-porous cylindrical constructs. It is envisioned that the fabricated constructs will develop porosity with the time-dependent biodegradation of the polymer blend. The mechanical properties will be sustained since the decrease in mechanical properties associated with the dissolution of the PLGA and the formation of the porous structure will be compensated with the new bone formation and ingrowth. To prove the hypothesis, we have systematically studied the effects of samples composition on the time-dependent dissolution behavior, pore formation, and mechanical properties of the engineered samples, in vitro. The highest initial (of as-prepared samples) values of the yield strength (0.021±0.002 GPa) and the Young's modulus (0.829±0.096 GPa) were exhibited by the samples containing 75 wt.% of PLGA. Increase of the PLGA concentration from 25 wt.% to 75 wt.% increased the rate of biodegradation by a factor of 3 upon 2 weeks in phosphate buffered saline (1× PBS). The overall porosity and the pore sizes increased with the dissolution time indicating that the formation of in-situ pores can indeed enable the migration of cells followed by vascularization and bone growth.

Summary Background Accelerating orthodontic tooth movement (OTM) through biologically effective methods, such as increasing osteoclast-mediated alveolar resorption, could effectively shorten treatment time. Objective To evaluate an injectable formulation containing receptor activator of nuclear factor kappa-B ligand (RANKL) on the OTM. Materials and methods We fabricated a RANKL formulation from 100 µl of 100 µg/ml RANKL adsorbed on 10 mg of poly(lactic acid-co-glycolic acid) microspheres embedded in a 10 wt% aqueous hydroxyethyl cellulose carrier gel. We characterized these formulations for the rate of RANKL release, and then tested for bioactivity using in vitro cell culture. In vivo OTM studies were conducted using 15 week old male Wistar rats for 14 days. We injected the RANKL formulations palatal to the left maxillary first molar and accomplished OTM with a nickel–titanium (NiTi) coil spring applying 5–8 g force. Control groups involved the application of NiTi coil spring with and without placebo formulation. The outcome measure included the distance of tooth movement, bone volume fraction, tissue density, and root volume determined with micro-computed tomography. We determined the amount of osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining. Results These formulations were able to sustain the release of RANKL for more than 30 days, and the released RANKL showed a positive effect on mice osteoclast precursor cells (RAW 264.7). Reported injectable RANKL formulations were effective in accelerating OTM compared with other control groups, with 129.2 per cent more tooth movement than no formulation and 71.8 per cent more than placebo formulation, corresponding with a significant increase in the amount of TRAP activity. We did not observe any significant differences in root resorption between the groups. Conclusion Our study shows a significant increase in OTM with injectable formulations containing RANKL.

Use of growth factors as biochemical molecules to elicit cellular differentiation is a common strategy in tissue engineering. However, limitations associated with growth factors, such as short half-life, high effective physiological doses, and high costs, have prompted the search for growth factor alternatives, such as growth factor mimics and other proteins. This work explores the use of insulin protein as a biochemical factor to aid in tendon healing and differentiation of cells on a biomimetic electrospun micro-nanostructured scaffold. Dose response studies were conducted using human mesenchymal stem cells (MSCs) in basal media supplemented with varied insulin concentrations. A dose of 100-ng/mL insulin showed increased expression of tendon markers. Synthetic-natural blends of various ratios of polycaprolactone (PCL) and cellulose acetate (CA) were used to fabricate micro-nanofibers to balance physicochemical properties of the scaffolds in terms of mechanical strength, hydrophilicity, and insulin delivery. A 75:25 ratio of PCL:CA was found to be optimal in promoting cellular attachment and insulin immobilization. Insulin insulin deliveryimmobilized fiber matrices also showed increased expression of tendon phenotypic markers by MSCs similar to findings with insulin supplemented media, indicating preservation of insulin bioactivity. Insulin functionalized scaffolds may have potential applications in tendon healing and regeneration.

Therapeutic biomolecules often require frequent administration and supramolecular dosing to achieve therapeutic efficiencies and direct infusion into treatment or defect sites results in inadequate physiological response and at times severe side effects or mis-targeting. Delivery systems serve several purposes such as increased circulatory time, increased biomolecule half-life, and incorporation of new innovations can enable highly specific cell targeting and improved cell and nucleus permeability. Poly(lactic acid) (PLA) has become a "material of choice" due to wide availability, reproducible synthetic route, customization, versatility, biodegradability and biocompatibility. Furthermore, PLA is amenable to a variety of fabrication methodologies and chemistries allowing an expansive library correlating physio-chemical properties, characteristics, and applications. This article discusses challenges to biomolecule delivery, and classical approaches of PLA based biomolecule delivery and targeting strategies under development and in trials.

This Article reports the fabrication and characterization of composite micro-nanostructured spiral scaffolds functionalized with nanofibers and hydroxyapatite (HA) for bone regeneration. The spiral poly(lactic acid-co-glycolic acid) (PLGA) porous microstructure was coated with sparsely spaced PLGA nanofibers and HA to enhance surface area and bioactivity. Polyelectrolyte-based HA coating in a layer-by-layer (LBL) fashion allowed 10–70 μM Ca(2+)/mm(2) incorporation. These scaffolds provided a controlled release of Ca(2+) ions up to 60 days with varied release kinetics accounting up to 10–50 μg. Spiral scaffolds supported superior adhesion, proliferation, and osteogenic differentiation of rat bone marrow stromal cells (MSCs) as compared to controls microstructures. Spiral micro-nanostructures supported homogeneous tissue ingrowth and resulted in bone-island formation in the center of the scaffold as early as 3 weeks in a rabbit ulnar bone defect model. In contrast, control cylindrical scaffolds showed tissue ingrowth only at the surface because of limitations in scaffold transport features.

Stem cell strategies and the use of electrical stimulation (ES) represent promising new frontiers for peripheral nerve regeneration. Composite matrices were fabricated by coating electrospun polycaprolactone/cellulose acetate micro-nanofibers with chitosan and ionically conductive (IC) polymers including, sulfonated polyaniline, and lignin sulfonate. These composite matrices were characterized for surface morphology, coating uniformity, ionic conductivity, and mechanical strength to explore as scaffold materials for nerve regeneration in conjunction with ES. Composite matrices measured conductivity in the range of 0.0049-0.0068 mS/m due to the uniform coating of sulfonated polymers on the micro-nanofibers. Thin films (2D) and composite fiber matrices (3D) of IC polymers seeded with human mesenchymal stem cells (hMSCs) were electrically stimulated at 0.5 V, 20 Hz for 1 h daily for 14 days to study the changes in cell viability, morphology, and expression of the neuronal-like phenotype. In vitro ES lead to changes in hMSCs' fibroblast morphology into elongated neurite-like structures with cell bodies for ES-treated and positive control growth factor-treated groups. Immunofluorescent staining revealed the presence of neuronal markers including β3-tubulin, microtubule-associated protein 2, and nestin in response to ES. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1792-1805, 2019.

This manuscript reports the characterization of molecularly self-assembled collagen nanofibers on a natural polymeric microporous structure and their ability to support stem cell differentiation in vitro and host tissue response in vivo. Specifically, cellulose acetate (CA) and poly(lactic acid-co-glycolic acid) (PLGA) produced two different microporous structures that were coated with self-assembled type I collagen (PLGAc and CAc). Though the total content of collagen was similar between the two materials after coating, the material chemistries significantly affected the molecular collagen self-assembly resulting in a more biomimetic nanofibrillar D-banding pattern on CA (mean fiber diameter of 80 nm) and a sheet like coating on PLGA (mean fiber diameter of 150 nm). Human mesenchymal stem cells (hMSCs) cultured on CA and CAc showed a significantly higher degree of in vitro osteoblastic progression, in contrast to PLGA and PLGAc. Furthermore, at 2 weeks post subcutaneous implantation, collagen coated CA materials showed increased matrix cellularization and enhanced biocompatibility. At 12 weeks both CA and CAc showed significantly greater matrix cellularity and immune acceptance compared to PLGA. This work illustrates the role of materials chemistry to dictate nanoscale protein assembly and its effect in terms of in vitro stem cell differentiation and in vivo host immune response. We also have proved that inclusion of nanoscale self-assembled ECM components such as collagen can enhance the stem cell inductive capabilities and biocompatibility of hydrophilic natural polymeric materials, making them viable alternatives to widely used synthetic polymers.

Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)--a novel gelatin Schiff base derivative--and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08 ± 1.5 MPa and 27.61 ± 4.3 MPa, respectively while the modified gelatin and their blends showed 15.63 ± 2.8 MPa and 24.47 ± 8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm(-1) disappeared following exposure to UV light indicating the regeneration of free NH2 group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength.

Scaffolds used for soft tissue regeneration are designed to mimic the native extracellular matrix (ECM) structurally and provide adequate mechanical strength and degradation properties. Scaffold architecture, porosity, stiffness and presence of soluble factors have been shown to influence human mesenchymal stem cells (hMSCs) differentiation along neuronal lineage. The present manuscript evaluated the performance of a composite scaffold comprised of electrospun polycaprolactone (PCL) nanofiber lattice coated with sodium alginate (SA) for neural tissue engineering. The nanofiber lattice was included in the scaffold to provide tensile strength and retain suture thread on the nerve graft. Sodium alginate was used to control matrix hydrophilicity, material stiffness and controlled release of biological molecules. The effect of SA molecular weight on the composite scaffold tensile properties, hMSCs adhesion, proliferation and neurogenic differentiation was evaluated. Both random and aligned composite scaffolds showed significantly higher tensile properties as compared to PCL fiber matrix alone indicating the reinforcement of SA hydrogel into fiber lattice. Low molecular weight SA coating because of its low viscosity resulted in uniform penetration into the fiber lattice and resulted in significantly higher tensile strength as compared to high molecular weight SA. Both composite scaffolds showed a controlled SA erosion rate and lost >95% of the SA coating over a period of 10 days under in vitro conditions. Composite scaffolds showed progressive hMSCs growth over 14 days and resulted in significantly higher amount of DNA content (almost double on day 7 and 14) as compared to control PCL fiber matrices. Immunostaining experiments showed higher and uniform expression of the neurotropic protein S-100 on composite scaffolds containing low molecular weight SA. These composite scaffolds may be suitable for peripheral nerve regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

A new series of novel nanostructured poly (aniline-co-m-aminobenzoic acid) copolymer has been synthesized by chemical oxidative in-situ polymerization method using dodecylbenzene sulphonic acid (DBSA) as a soft template. The synthesized copolymers were characterized by Fourier Transform Infrared spectroscopy, Ultraviolet visible spectroscopy, X-ray diffraction and scanning electron microscopy. The infrared spectrum shows the characteristic peaks confirming the formation of the copolymer. The ultraviolet visible spectrum shows the π to π∗ transition and n to π∗ transition. X-ray diffraction pattern confirms the amorphous nature of the polymer. Scanning electron microscopic images show the new morphology of spherical granular sponge like structures in the range of 100 to 200 nm. Conducting properties of the copolymers were studied using four probe method. Copolymers doped with DBSA showed an increased conductivity in the order of 10–4 S/cm. These copolymers are found to be more soluble in polar solvents comparing to polyaniline homopolymer.

Cartilage degeneration is the major cause of disability and poses several challenges to repair and regenerate. Conventional surgical treatments often induce fibrous tissues and compromise its function. Alternative tissue engineering strategies utilized scaffolds, factors and cells alone or in combination with some degree of success. This study reports the use of nanostructured biomimetic scaffold system in regulating the rat bone marrow stem cells (rBMSCs) differentiation into chondrogenic lineage in vitro. The biometric scaffold is essentially a micro-porous polycaprolactone (PCL) spiral structure decorated with sparsely spaced bioactive PCL nanofibers. The bioactivity stems from the use of two major components of hyaline cartilage extracellular matrix (ECM) namely chondroitin sulfate (CS) and hyaluronic acid (HYA). The PCL spiral structure was surface functionalized with PCL nanofibers encapsulated with CS (20% (w/w)) and HYA (0.2% (w/w)). In order to retain and sustain the release of CS and HYA nanofibers were cross-linked using carbodiimide chemistry. This study also evaluated the effect of nanofiber alignment on rBMSCs differentiation and evaluated the production of characteristic hyaline cartilage proteins namely collagen type II and aggrecan in vitro up to 28 days. Rat bone marrow derived stem cells cultured on the aligned nanofibers expressed significantly elevated levels of collagen type II and aggrecan secretions (western blots) as compared to scaffolds decorated with random fibers and tissue culture polystyrene (TCPS). This fiber alignment dependent expression of collagen type II and aggrecan secretion were further confirmed through immunofluorescence staining. This biomimetic and bioactive scaffold may serve as a serve as an efficient scaffold system for cartilage regeneration.

Scaffold architecture, surface topography, biochemical and mechanical cues have been shown to significantly improve cellular events and in vivo tissue regeneration. Specifically electrospun nanofiber matrices have gained tremendous interest due to their intrinsic structural resemblance to native tissue extracellular matrix (ECM). The present study reports on the electrospun nanofiber matrices of polycaprolactone (PCL)-chitosan (CS) blends and effect of type I collagen surface functionalization in regulating rat bone marrow derived stromal cells (rBMSCs) differentiation into osteogenic lineage. Collagen was covalently attached to blend nanofibers via carbodiimide (EDC) coupling. Bead-free smooth nanofibers (diameter-700-850 nm) obtained at the optimized conditions of polymer concentration and electrospinning parameters were used for the study. EDC collagen coupling resulted in 0.120+/-0.016 micro g of collagen immobilization onto a 1 cm2 area of the PCL/CS nanofibers, which was 2.6-folds higher than the amount of collagen that can be retained by physical adsorption. Significantly improved rBMSCs adhesion, spreading, proliferation and osteogenic differentiation was observed on the collagen functionalized COL-PCULCS nanofiber matrices as compared to control groups. Osteogenic phenotypic markers such as alkaline phosphatase (ALP) activity and mineralization were found to be significantly higher on COL-PCL/CS nanofiber matrices as compared to controls. Elevated gene expression profiles of osteogenic markers such as osteocalcin (0CN), osteopontin (OPN) and ALP further corroborate the osteoinductive nature of the collagen functionalized PCL/CS nanofiber matrices. These fiber matrices and modification techniques could be extended to other scaffold systems for tissue engineering applications.

A novel polymer poly(caprolactone triol succinate) (PPCLSu) was synthesized from monomers polycaprolactone triol and succinic acid by direct polycondensation. The tensile strength of PPCLSu was found to be 0.33 60.03 MPa with an elongation of 47.8 61.9%. These elastomers lost about 7% of their original mass in an in vitro degradation study conducted in phosphate-buffered saline (PBS) at 37 � C up to 10 weeks. Three-dimensional (3D) porous scaffolds were created by a porogen-leaching method and these constructs were evaluated for primary rat osteoblast (PRO) proliferation and phenotype development in vitro. This elastomer pro- moted primary rat osteoblast adhesion, proliferation and increased expression of alkaline phosphatase, an early marker of osteoblastic phenotype. These preliminary results suggest that PPCLSu may be a good candidate material for scaffolding applications in tissue regeneration. V C 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3770-3777, 2013

Scaffold based bone tissue engineering (BTE) has made great progress in regenerating lost bone tissue. Materials of natural and synthetic origin have been used for scaffold fabrication. Scaffolds derived from natural polymers offer greater bioactivity and biocompatibility with mammalian tissues to favor tissue healing, due to their similarity to native extracellular matrix (ECM) components. Often it is a challenge to fabricate natural polymer based scaffolds for BTE applications without compromising their bioactivity, while maintaining adequate mechanical properties. In this work, we report the fabrication and characterization of cellulose and collagen based micro-nano structured scaffolds using human osteoblasts (HOB) for BTE applications. These porous micro-nano structured scaffolds (average pore diameter 190 +/- 10 microm) exhibited mechanical properties in the mid range of human trabecular bone (compressive modulus 266.75 +/- 33.22 MPa and strength 12.15 3 +/- 2.23 MPa). These scaffolds supported the greater adhesion and phenotype maintenance of cultured HOB as reflected by higher levels of osteogenic enzyme alkaline phosphatase and mineral deposition compared to control polyester micro-nano structured scaffolds of identical pore properties. These natural polymer based micro-nano structured scaffolds may serve as alternatives to polyester based scaffolds for BTE applications.

The compatibility and biological efficacy of biomedical implants can be enhanced by coating their surface with appropriate agents. For predictable functioning of implants in situ, it is often desirable to obtain an extremely uniform coating thickness without effects on component dimensions or functions. Conventional coating techniques require rigorous processing conditions and often have limited adhesion and composition properties. In the present study, the authors report a novel precision electrospraying technique that allows both degradable and nondegradable coatings to be placed. Thin metallic slabs, springs, and biodegradable sintered microsphere scaffolds were coated with poly(lactide-co-glycolide) (PLAGA) using this technique. The effects of process parameters such as coating material concentration and applied voltage were studied using PLAGA and poly(ethylene glycol) coatings. Morphologies of coated surfaces were qualitatively characterized by scanning electron microscopy. Qualitative observations suggested that the coatings were composed of particles of various size/shape and agglomerates with different porous architectures. PLAGA coatings of uniform thickness were observed on all surfaces. Spherical nanoparticle poly(ethylene glycol) coatings (462-930 nm) were observed at all concentrations studied. This study found that the precision electrospraying technique is elegant, rapid, and reproducible with precise control over coating thickness (mum to mm) and is a useful alternative method for surface modification of biomedical implants.

Grafting of acrylamide onto guar gum is achieved by Ce(IV) induced free-radical polymerization to prepare interpenetrating polymer network (IPN) beads of polyacrylamide-g-guar gum with sodium alginate by crosslinking with glutaraldehyde. Two widely used pesticides, solid chlorpyrifos and liquid fenvelarate, are loaded up to 60–70% efficiency in the IPN beads. The polymer and beads are characterized by Fourier transform IR spectroscopy to confirm grafting and to understand the possible interactions between the pesticides and the polymer matrix. Scanning electron microscopy is used to study the morphology of the beads. Equilibrium swelling experiments indicate that the swelling of the beads decreases with an increase in crosslinking, as well as an increase in pesticide loading. The in vitro release studies are performed under static conditions, and the release data are fitted to an empirical relationship to evaluate the transport parameters. Diffusion coefficients are calculated for the transport of pesticides through the polymeric beads using the initial and later time approximation methods. These values show a decrease with increasing crosslinking and increasing pesticide loading. Long-term diffusion coefficients as computed by Fick's equations are found to be smaller in magnitude when compared to the initial time diffusion coefficients. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 451–457, 2003

The grafting of acrylamide onto a chitosan backbone was carried out at three acrylamide concentrations (polymer/monomer ratio = 1:1, 1:2, and 1:3). The synthesis of the grafted polymer was achieved by K2S2O8-induced free-radical polymerization. Microspheres of polyacrylamide-g-chitosan crosslinked with glutaraldehyde were prepared to encapsulate nifedipine (NFD), a calcium channel blocker and an antihypertensive drug. The microspheres of polyacrylamide-g-chitosan were produced by a water-in-oil emulsion technique with three different concentrations of glutaraldehyde as the crosslinking agent. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to characterize the grafted copolymers, and the microspheres were prepared from them. FTIR and DSC were also used to analyze the extent of crosslinking. The microspheres were characterized by the particle size; the water transport into these microspheres, as well as the equilibrium water uptake, were studied. Scanning electron microscopy confirmed the spherical nature of the particles, which had a mean particle size of 450 μm. Individual particle dynamic swelling experiments suggested that with an increase in crosslinking, the transport became case II. The release of NFD depended on the crosslinking of the network and on the amount of drug loading. Calculating the drug diffusion coefficients with the initial time and later time approximation method further supported this. The drug release in all 27 formulations followed case II transport, and this suggested that the time dependence of the NFD release followed zero-order kinetics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2940–2949, 2003

Electrospun nanofiber matrices have attracted a great deal of attention as matrices for skin repair and regeneration. The current manuscript reports the fabrication and characterization of a bioactive polycaprolactone (PCL) fiber matrix for its ability to deliver multiple factors. Bioactive PCL matrices were created by incorporating a model angiogenic factor and a model antibiotic drug. Chitosan coating on the fiber matrices significantly improved the ability to hold moisture and contributed to antibiotic activity. These fiber matrices have a modulus of 5.8 61.3 MPa and matrices subjected to degradation over 4 weeks did not lose their tensile properties due to slow degradation rate. Chitosan coating avoided the initial burst release commonly associated with fiber matrices and only 60% of the encapsulated drug was released over a period of 15 days. Control PCL-chitosan matrices were able to reduce Staphylococcus aureus (S. aureus) growth both in static and dynamic condition as compared to formulations with 50 mg gentamicin. In general, all the fiber matrices were able to support fibroblast growth and maintained normal cell morphology. Such bioactive ban- dages may serve as versatile and less expensive alternatives for the treatment of complex wounds. V C 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41879.

Novel copolymers of poly(aniline-co-m-chloroaniline)-doped dodecylbenzenesulphonic acid (DBSA) with embedded silver nanoparticles were synthesised using the in situ chemical oxidative method. The structural properties of the copolymers were characterised using the UV-VIS and FTIR spectroscopic methods. The crystalline nature of the copolymer was demonstrated by way of the X-ray diffraction (XRD) pattern. Scanning electron microscopy (SEM) revealed the presence of particle agglomerates measuring 50 nm to 100 nm on the surface of the nanocomposites. The electrical conductivity of the copolymer was dependent on the monomer composition and was found to be in the range of 10−2 S cm−1 to 10−6 S cm−1 with an increasing chloroaniline content and exhibiting improved solubility.

Microspheres of polyacrylamide-grafted-chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti-inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug-entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug-release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non-Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug-diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non-Fickian trend and the diffusion was relaxation-controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003

Acrylic-based copolymers of methyl methacrylate (MMA) and methacrylic acid (MAA) have been prepared by solution and bulk polymerization techniques using benzoyl peroxide (BPO) as an initiator. Three polymers were prepared with a varying ratio of MMA/MAA. In an effort to increase the hydrophilicity of the matrix, one MMA/MAA polymer was prepared by adding an additional amount of 2-hydroxy ethyl methacrylate (HEMA). All the polymers were crosslinked in situ by ethylene glycol dimethacrylate (EGDMA). These polymers were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Viscous flow characteristics were determined from solution viscosity and rheological measurements. Dynamic and equilibrium swelling experiments were carried out under varying pH conditions (i.e., 0.1N NaOH, 0.1N HCl, and double-distilled water). Partially crosslinked hydrogels show varying hydrophilicity because of the presence of carboxylic acid groups making them pH-responsive. Swelling increased with an increasing number of —COOH groups on the polymer backbone and the hydrophilicity varied with changing pH. Cypermethrin, a widely used pesticide, and cupric sulfate, a model micronutrient, were loaded into these pH-sensitive hydrogels to investigate their controlled release characteristics. The in vitro release rates of both compounds have been carried out under static dissolution conditions at 30°C. Release data have been fitted to an empirical relation to estimate transport parameters. The release results have been discussed in terms of the varying hydrophilicity of the hydrogel network polymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 394–403, 2003

Polyacrylamide-grafted sodium alginate (PAAm-g-Na-Alg) copolymeric membranes have been prepared, characterized, and used in the pervaporation separation of 10–80 mass % water-containing tetrahydrofuran mixtures. Totally three membranes were prepared: (1) neat Na-Alg with 10 mass % of polyethylene glycol (PEG) and 5 mass % of polyvinyl alcohol (PVA), (2) 46 % grafted PAAm-g-Na-Alg membrane containing 10 mass % of PEG and 5 mass % of PVA, and (3) 93 % grafted PAAm-g-Na-Alg membrane containing 10 mass % of PEG and 5 mass % of PVA. Using the transport data, important parameters like permeation flux, selectivity, pervaporation separation index, swelling index, and diffusion coefficient have been calculated at 30°C. Diffusion coefficients were also calculated from sorption gravimetric data of water–tetrahydrofuran mixtures using Fick's equation. Arrhenius activation parameters for the transport processes were calculated for 10 mass % of water in the feed mixture using flux and diffusion data obtained at 30, 35, and 40°C. The separation selectivity of the membranes ranged between 216 and 591. The highest permeation flux of 0.677 kg/m2 h was observed for 93% grafted membrane at 80 mass % of water in the feed mixture. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 272–281, 2002

Interpenetrating network polymeric beads of poly(vinyl alcohol)-grafted-acrylamide with sodium alginate have been prepared by crosslinking with glutaraldehyde. Cypermethrin, a widely used pesticide, was loaded with 80% efficiency in these hydrogel beads. The beads were characterized by Fourier transform infrared spectroscopy to confirm the grafting. Scanning electron microscopy was used to know the morphology of the beads. Equilibrium swelling experiments indicated that swelling of the beads decreased with an increase in crosslinking. The in vitro release studies were performed under static conditions and the release data have been fitted to an empirical relation to estimate the transport parameters. The diffusion coefficients have been calculated for the transport of pesticide through the polymeric beads using the initial time approximation method. These values showed decrease with increasing crosslinking as well as increasing pesticide loading. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 552–560, 2002; DOI 10.1002/app.10306

This paper reports solubility and partition coefficient data for the structurally similar pesticides, fenvalerate and cypermethrin, measured by UV spectrophotometry in binary mixtures of methanol and water at different temperatures. The solubility of both pesticides is much higher in methanol than in water at all temperatures. Partition coefficients were also measured between water+heptanol immiscible mixtures at 298.15K, and these data show a decrease with increasing composition of methanol in water.

Microspheres of chitosan crosslinked with three different crosslinking agents viz, glutaraldehyde, sulphuric acid and heat treatment have been prepared to encapsulate diclofenac sodium (DS). Chitosan microspheres are produced in a w/o emulsion followed by crosslinking in the water phase by one of the crosslinking methods. Encapsulation of DS has been carried out by soaking the already swollen crosslinked microspheres in a saturated solution of DS. Microspheres are further characterized by FTIR, x-RD and SEM. The in-vitro release studies are performed in 7.4 pH buffer solution. Microspheres produced are spherical and have smooth surfaces, with sizes ranging between 40-230 microm, as evidenced by SEM. The crosslinking of chitosan takes place at the free amino group in all the cases, as evidenced by FTIR. This leads to the formation of imine groups or ionic bonds. Polymer crystallinity increases after crosslinking, as determined by x-RD. The method adopted for drug loading into the microspheres is satisfactory, and up to 28-30% w/w loading is observed for the sulphuric acid-crosslinked microspheres, whereas 23-29 and 15-23% of loadings are obtained for the glutaraldehyde (GA)- and heat-crosslinked microspheres, respectively. Among all the systems studied, the 32% GA crosslinked microspheres have shown the sloxvest release i.e. 41% at 420 min, and a fastest release of 81% at 500 min is shown by heat crosslinking for 3 h. Drug release from the matrices deviates slightly from the Fickian process.

This article presents our preliminary experimental data on the release kinetics and encapsulation efficiency of urea formaldehyde (UF) crosslinked matrices of starch (St), guar gum (GG), and starch + guar gum (St + GG) for the controlled release of solid (chlorpyrifos) and liquid (neem seed oil) pesticides. The data reveal variable release rates in relation to the polymer type and especially the pesticide type. It is possible to slow the release rates of pesticides using cheaply available materials such as starch and guar gum. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 2863–2866, 2001

Several polymers of both natural and synthetic origin have been used for a variety of biomedical applications including pharmaceutical preparations, drug targeting, imaging, drug delivery, prosthetics, and tissue engineering scaffolds. Due to their reproducible characteristics in terms of their molecular weight, degradation and mechanical properties, synthetic polymers are attractive for a variety of the aforementioned applications. However, synthetic polymers from the biological standpoint, synthetic polymers often lack much-desired bioactivity and biocompatibility, which may translate into adverse side effects. Natural polymers on the other hand are abundant and resemble the components present in biological extracellular matrices. Thus, natural polymers are readily accepted by the body and possess high bioactivity and biocompatibility. Natural polymers can be divided into three major classes according to their chemical structure: (i) polysaccharides, (ii) proteins, and (iii) polyesters. This chapter presents an overview of the polysaccharide-based biomaterials, their structure property, and applications in the area of drug delivery and tissue engineering. Particular emphasis is given to polysaccharides such as (i) hyaluronic acid (HA), (ii) chondroitin sulfate, (iii) chitin and chitosan, (iv) alginates, and (v) cellulose. These polymers and their popular derivatives are also discussed in the context of their chemical and biological properties. Polysaccharides in their native form may not be able to provide all the desired properties for a particular biomedical application. Thus, the chapter also focuses on the polysaccharide derivatives and their blend with other polymers for a variety of biomedical applications.

Polyurethanes (PURs) are versatile class of polymers with a great control over their physicochemical properties. They are constituted with hard and soft segments, and therefore, they are called segmented PURs, and based on the nature of segment composition, their properties can be greatly altered to meet the requirements for a particular biomedical applications. Segmented PURs are designed with well-defined degradation and mechanical properties combined with excellent biocompatibility that makes them attractive for the development of drug delivery, tissue engineering, and medical devices. This chapter highlights the synthetic aspects of the PURs and methods related to their characterization in terms of physicochemical properties using in vitro and in vivo techniques and examples of relevant biomedical applications. This chapter also includes details on poly(ether urethanes), poly(ester urethanes), poly(carbonate urethanes), poly(siloxane urethanes), surface-modified PURs, and composite PURs in various fields for biomedical applications are addressed.

Injectable hydrogels have attracted a great deal of attention as cell carriers and bioactive agents in regenerative medicine due to their ability to fill complex three-dimensional (3D) tissue gaps and relative ease of in vivo administration. Polysaccharide-based hydrogels can provide microenvironments that favor tissue regeneration and biocompatibility due to their chemical similarities with native extracellular matrix components. This manuscript reports the in vitro application of an injectable chitosan-based polysaccharide hydrogel for cell and protein delivery. Crosslinked hydrogels were produced by the reaction between the amino functionality of chitosan and the aldehyde of dextran aldehyde resulting in an imine bond (Schiff's base) formation in aqueous solutions. This approach eliminated the use of additional crosslinking agents which may pose undesired side effects regarding cytotoxicity and biocompatibility. Additionally, we demonstrate versatility of the gel in terms of its fabrication, and ability to alter mechanical properties by changing the crosslinking extent due to aldehyde content. Bovine serum albumin (BSA), used as a model protein, followed a steady release pattern from the gel. BSA release was dependent on the extent of hydrogel crosslinking. Increase in crosslinking extent resulted in improved mechanical properties and sustained release of BSA. Human fetal osteoblasts encapsulated into the hydrogel showed at least 70% viability and continued to proliferate under in vitro culture. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39934.

Bone is a natural composite comprised of hierarchically arranged collagen fibrils, hydroxyapatite and proteoglycans in the nanometer scale. This preliminary study reports the fabrication of biodegradable poly[bis(ethyl alanato)phosphazene]-nanohydroxyapatite (PNEA-nHAp) composite nanofiber matrices via electrospinning. Binary solvent compositions of THF and ethanol were used as a spinning solvent to attain better nanohydroxyapatite dispersibility in PNEA solution. These nanocomposites were characterized for morphology, nHAp distribution and content using spectroscopy and gravimetric estimations. Composite nanofibers fabricated in the diameter range of 100-310 nm could encapsulate 20-40 nm nHAp crystals. A better composite nanofiber yield was obtained for 50% (w/w) nHAp experimental loadings. Incremental experimental loading beyond 60% (w/w) hindered electrospinning due to polymer-nHAp phase separation. Composites nanofibers had a rougher surface and nodules along the length of the fibers suggesting nHAp encapsulation. Further, characterization via energy dispersive X-ray spectroscopy and X-ray mapping confirmed the nHAp encapsulation. Providing cells with a natural bone like environment with a fibrillar structure and natural hydroxyapatite can enhance bone tissue regeneration/repair.

The long-term goal of this work is to develop biomimetic polymer-based systems for bone regeneration that both allow for neutral pH degradation products and have the ability to nucleate bonelike apatite. In this study, the etheric biodegradable polyphosphazene, poly[(50%ethyl glycinato)(50%methoxyethoxyethoxy)phosphazene] (PNEG(50)MEEP(50)) was blended with poly(lactide-co-glycolide) PLAGA and studied their ability to produce high-strength degradable biomaterials with bioactivity. Accordingly, two blends with weight ratios of PNEG(50)MEEP(50) to PLAGA 25:75 (BLEND25) and 50:50 (BLEND50) were fabricated using a mutual solvent approach. Increases in PNEG(50)MEEP(50) content in the blend system resulted in decreased elastic modulus of 779 MPa when compared with 1684 MPa (PLAGA) as well as tensile strength 7.9 MPa when compared with 25.7 MPa (PLAGA). However, the higher PNEG(50)MEEP(50) content in the blend system resulted in higher Ca/P atomic ratio of the apatite layer 1.35 (BLEND50) when compared with 0.69 (BLEND25) indicating improved biomimicry. Furthermore, these blends supported primary rat osteoblast adhesion and proliferation with an enhanced phenotypic expression when compared with PLAGA. These findings establish the suitability of PNEG(50)MEEP(50)-PLAGA biodegradable blends as promising bioactive materials for orthopedic applications.

Electrospun fiber matrices composed of scaffolds of varying fiber diameters were investigated for potential application of severe skin loss. Few systematic studies have been performed to examine the effect of varying fiber diameter electrospun fiber matrices for skin regeneration. The present study reports the fabrication of poly[lactic acid-co-glycolic acid] (PLAGA) matrices with fiber diameters of 150-225, 200-300, 250-467, 500-900, 600-1,200, 2,500-3,000 and 3,250-6,000 nm via electrospinning. All fiber matrices found to have a tensile modulus from 39.23+/-8.15 to 79.21+/-13.71 MPa which falls in the range for normal human skin. Further, the porous fiber matrices have porosity between 38 to 60% and average pore diameters between 10 to 14 microm. We evaluated the efficacy of these biodegradable fiber matrices as skin substitutes by seeding them with human skin fibroblasts (hSF). Human skin fibroblasts acquired a well spread morphology and showed significant progressive growth on fiber matrices in the 350-1,100 nm diameter range. Collagen type III gene expression was significantly up-regulated in hSF seeded on matrices with fiber diameters in the range of 350-1,100 nm. Based on the need, the proposed fiber skin substitutes can be successfully fabricated and optimized for skin fibroblast attachment and growth.

Biodegradable polymeric scaffolds are widely used as a temporary extracellular matrix in tissue engineering and regenerative medicine. By physical adsorption of biomolecules on scaffold surface, physical entrapment of biomolecules in polymer microspheres or hydrogels, and chemical immobilization of oligopeptides or proteins on biomaterials, biologically active biomaterials and scaffolds can be derived. These bioactive systems show great potential in tissue engineering in rendering bioactivity and/or specificity to scaffolds. This review highlights some of the biologically active chitosan systems for tissue engineering application and the associated strategies to develop such bioactive chitosan systems.

Previously we demonstrated the ability of ethyl glycinato substituted polyphosphazenes to neutralize the acidic degradation products and control the degradation rate of poly(lactic acid-glycolic acid) by blending. In this study, blends of high strength poly[(50% ethyl alanato) (50% p-phenyl phenoxy) phosphazene] (PNEA50PhPh50) and 85:15 poly(lactic acid-glycolic acid) (PLAGA) were prepared using a mutual solvent approach. Three different solvents, methylene chloride (MC), chloroform (CF) and tetrahydrofuran (THF) were studied to investigate solvent effects on blend miscibility. Three different blends were then fabricated at various weight ratios namely 25:75 (BLEND25), 50:50 (BLEND50), and 75:25 (BLEND75) using THF as the mutual solvent. The miscibility of the blends was evaluated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Among these, BLEND25 was miscible while BLEND50 and BLEND75 were partially miscible. Furthermore, BLEND25 formed apatite layers on its surface as evidenced in a biomimetic study performed. These novel blends showed cell adhesion and proliferation comparable to PLAGA. However, the PNEA50PhPh50 component in the blends was able to increase the phenotypic expression and mineralized matrix synthesis of the primary rat osteoblasts (PRO) in vitro. Blends of high strength poly[(50% ethyl alanato) (50% p-phenyl phenoxy) phosphazene] (PNEA50PhPh50) and 85:15 poly(lactic acid-glycolic acid) (PLAGA) are promising biomaterials for a variety of musculoskeletal applications.

Recently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide) (pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-responsive hydrogels, particularly those that respond to temperature and pH, and their applications in drug delivery.

The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their β-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three-dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10-15% after 24 weeks. A typical stress-strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid-glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration.