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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.

Despite progress, clinical translation of tissue engineering (TE) products/technologies is limited. A significant effort is underway to develop biomaterials and cells through a minimally modified process for clinical translation of TE products. Recently, bone marrow aspirate (BMA) was identified as an autologous source of cells for TE applications and is currently being tested in clinical therapies, but the isolation methods need improvement to avoid potential for contamination and increase progenitor cell yield. To address these issues, we reproducibly processed human peripheral blood (PB) and BMA to develop autologously derived biomaterials and cells. We demonstrated PB-derived biomaterial/gel cross-linking and fibrin gel formation with varied gelation times as well as biocompatibility through support of human bone marrow-derived stem cell survival and growth in vitro. Next, we established a plastic culture-free process that concentrates and increases the yield of CD146(+)/CD271(+) early mesenchymal progenitor cells in BMA (concentrated BMA [cBMA]). cBMA exhibited increased colony formation and multipotency (including chondrogenic differentiation) in vitro compared with standard BMA. PB-derived gels encapsulated with cBMA also demonstrated increased cell proliferation and enhanced mineralization when assessed for bone TE in vitro. This strategy can potentially be developed for use in any tissue regeneration application; however, bone regeneration was used as a test bed for this study. IMPACT STATEMENT: Tissue engineering (TE) is a rapidly growing field; however, clinical translation of TE products remains challenging. Autologously sourced bone marrow aspirate (BMA) and peripheral blood (PB) offer relative ease of harvesting and host compatibility and require minimal/no regulatory approvals. In this study, concentration of BMA led to the enrichment of early progenitor cells, which can potentially improve TE outcomes. Furthermore, concentrating BMA in combination with calcium-mediated, cross-linked fibrin gels derived from PB presented enhanced proliferation and osteogenic potential for a minimally modified bone TE strategy. These findings demonstrate the potential utilization of BMA in combination with PB for development of clinically translatable TE strategies for regeneration of different tissues.

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.

Allografts are commonly used as an alternative to autografts for bone defect repair, but in some instances suffer from reduced host incorporation that can lead to complications 5 and 10 years post-implantation. We have previously demonstrated that using a thin polymeric coating along the outer surfaces of cortical bone can improve the biofunctionality of devitalized bone allografts by permitting the upload and delivery of growth factors from the thin coating. Here, we expand on our previous work to develop a methodology to coat porous trabecular allografts with a similar polymer coating with careful attention to maintaining an open pore network within the allograft and establishing the effect of varying the polymer solution viscosity on coating extent and thickness. Results indicate that varying the polymer solution viscosity by changing the polymer to solvent ratio used to coat the samples allows for variations in coating thickness and extent of surface area coverage, each perhaps allowing for greater control over growth factor loading and release concentration and kinetics. Further, we develop a dynamic coating method that produces a continuous and consistent coating throughout the pore structure vs. the previously used static method that resulted in a discontinuous coating throughout the pore network. The work demonstrated here provides important techniques for varying the payload of polymer-coated, factor-loaded trabecular allografts which would provide another tool to the orthopedic surgeon when healing large-scale defects with trabecular allograft. Large scale bone defects are traditionally treated with either autografts or allografts. Allografts suffer from poor incorporation in part due to the processing undertaken to render them safe to transplant from one individual to another. We sought to add back some of the biological functionality that is removed in this processing by loading growth factors into a very thin polymeric coating that we apply to the surface of the allograft. Our results indicate a thin, continuous polymeric coating throughout the trabecular allograft, with the amount of this coating varying as we vary the concentration of this polymer solution prior to coating. Future studies will evaluate the ability of this varied concentration of polymer coating to permit the delivery of varying amounts of growth factors, imparting a greater degree of control over the amount of growth factor delivered from the coated allografts.

Artificial nerve guidance conduits (NGCs) are being investigated as an alternative to autografts, since autografts are limited in supply. A polycaprolactone (PCL)-based spiral NGC with crosslinked laminin on aligned nanofibers was evaluated in vivo post a successful in vitro assessment. PC-12 cell assays confirmed that the aligned nanofibers functionalized with laminin were able to guide and enhance neurite outgrowth. In the rodent model, the data demonstrated that axons were able to regenerate across the critical nerve gap, when laminin was present. Without laminin, the spiral NGC with aligned nanofibers group resulted in a random cluster of extracellular matrix tissue following injuries. The reversed autograft group performed best, showing the most substantial improvement based on nerve histological assessment and gastrocnemius muscle measurement. Nevertheless, the recovery time was too short to obtain meaningful data for the motor functional assessments. A full motor recovery may take up to years. An interesting observation was noted in the crosslinked laminin group. Numerous new blood capillary-like structures were found around the regenerated nerve. Owing to recent studies, we hypothesized that new blood vessel formation could be one of the key factors to increase the successful rate of nerve regeneration in the current study. Overall, these findings indicated that the incorporation of laminin into polymeric nerve conduits is a promising strategy for enhancing peripheral nerve regeneration. However, the best combination of contact-guidance cues, haptotactic cues, and chemotactic cues have yet to be realized. The natural sequence of nerve regeneration should be studied more in-depth before modulating any strategies.

Soft tissue refers to those that support, connect, or surround the body’s organs. This includes muscles, ligaments, tendons, nerve, fat, fascia, and blood vessels. Soft tissues are susceptible to injuries, especially for athletes and the elderly population leading to an increase in the demand for surgeries. However, surgical intervention cannot provide full biological restoration of the tissues, resulting in scar formation rather than regeneration. Tissue engineering aims to develop tissue substitutes by employing engineered extracellular matrix (ECM), cells and factors alone or in combination to overcome limitations in tissue healing. It is expected that the demand for tissue-engineered products and approaches addresses clinically unmet needs in soft-tissue regeneration. The ultimate goal of tissue engineering is to design bioactive implanted scaffolds that mimic the native ECM of the target tissue structurally. These designed scaffolds provide the required mechanical and structural properties that aid the damaged tissue. Nanofiber matrices derived from natural and synthetic materials closely mimic the natural ECM structurally and compositionally. These matrices provide large surface area to volume ratio and adjustable pore dimeter and mechanical strength to enable the soft-tissue repair and subsequent soft-tissue regeneration. Therefore, nanofiber matrices are popularly used for a variety of tissue engineering applications.

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.

Successful tissue regeneration strategies focus on the use of novel biomaterials, structures, and a variety of cues to control cell behavior and promote regeneration. Studies discovered how biomaterial/ structure cues in the form of biomaterial chemistry, material stiffness, surface topography, pore, and degradation properties play an important role in controlling cellular events in the contest of in vitro and in vivo tissue regeneration. Advanced biomaterials structures and strategies are developed to focus on the delivery of bioactive factors, such as proteins, peptides, and even small molecules to influence cell behavior and regeneration. The present article is an effort to summarize important findings and further discuss biomaterial strategies to influence and control cell behavior directly via physical and chemical cues. This article also touches on various modern methods in biomaterials processing to include bioactive factors as signaling cues to program cell behavior for tissue engineering and regenerative medicine.

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.

Peripheral nerve injury accounts for roughly 2.8% of all trauma patients with an annual cost of 7 billion USD in the U.S. alone. Current treatment options rely on surgical intervention with the use of an autograft, despite associated shortcomings. Engineered nerve guidance conduits, stem cell therapies, and transient electrical stimulation have reported to increase speeds of functional recovery. As an alternative to the conduction effects of electrical stimulation, we have designed and optimized a nerve guidance conduit with aligned microchannels for the sustained release of a small molecule drug that promotes nerve impulse conduction. A biodegradable chitosan structure reinforced with drug-loaded halloysite nanotubes (HNT) was formed into a foam-like conduit with interconnected, longitudinally-aligned pores with an average pore size of 59.3 ± 14.2 μm. The aligned composite with HNTs produced anisotropic mechanical behavior with a Young's modulus of 0.33 ± 0.1 MPa, very similar to that of native peripheral nerve. This manuscript reports on the sustained delivery of 4-Aminopyridine (4AP, molecular weight 94.1146 g/mol), a potassium-channel blocker as a growth factor alternative to enhance the rate of nerve regeneration. The conduit formulation released a total of 30 ± 2% of the encapsulated 4AP in the first 7 days. Human Schwann cells showed elevated expression of key proteins such as nerve growth factor, myelin protein zero, and brain derived neurotrophic factor in a 4AP dose dependent manner. Preliminary in vivo studies in a critical-sized sciatic nerve defect in Wistar rats confirmed conduit suturability and strength to withstand ambulatory forces over 4 weeks of their implantation. Histological evaluations suggest conduit biocompatibility and Schwann cell infiltration and organization within the conduit and lumen. These nerve guidance conduits and 4AP sustained delivery may serve as an attractive strategy for nerve repair and regeneration.

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.

Focal chondral defects that result from traumatic injuries to the knee remain one of the most common causes of disability in patients. Current solutions for healing focal cartilage defects are mainly limited by the production of inferior cartilage-like tissue and subsequent delamination due to incomplete healing of the subchondral bone. In this experiment a polymeric osteochondral implant for guiding autologous bone marrow stem cells (BMSCs) to populate the scaffold to create distinctive bone and cartilage tissue is used. The cartilage component presents bioactive aligned nanofibers containing chondroitin sulfate and hyaluronic acid while the bone component includes hydroxyapatite to promote chondrogenic and osteogenic differentiation of the rat BMSCs in vitro. The different cartilage and bone components resulted in the elevated expression of osteogenic markers such as bone sialoprotein, runt related transcription factor 2, and bone morphogenetic protein 2 in the deeper bone layer and chondrogenic markers such as collagen type II and aggrecan in the cartilage layer. Through immunofluorescence imaging, the alignment of the secreted collagen type II fibrils and aggrecan was visualized and quantified on the cartilage component of the scaffold. These current studies show that the biodegradable biphasic osteochondral implant may be effective in promoting more hyaline-like tissue to fill in chondral defects of the knee.

Bone tissue engineering (BTE) strategies utilize biodegradable polymeric matrices alone or in combination with cells and factors to provide mechanical support to bone, while promoting cell proliferation, differentiation, and tissue ingrowth. The performance of mechanically competent, micro-nanostructured polymeric matrices, in combination with bone marrow stromal cells (BMSCs), was evaluated in a critical sized bone defect. Cellulose acetate (CA) was used to fabricate a porous micro-structured matrix. Type I collagen was then allowed to self-assemble on these micro-structures to create a natural polymer-based, micro-nanostructured matrix (CAc). Poly (lactic-co-glycolic acid) (PLGA) matrices with identical micro-structures served as controls. Significantly higher number of implanted host cells were distributed in the natural polymer based micro-nanostructures with greater bone density and more uniform cell distribution. Additionally, a two-fold increase in collagen content was observed with natural polymer based scaffolds. This study establishes the benefits of natural polymer derived micro-nanostructures in combination with donor derived BMSCs to repair and regenerate critical sized bone defects. Natural polymer based materials with mechanically competent micro-nanostructures may serve as an alternative material platform for bone regeneration.

Conductive polymers have found extensive application in fuel cells, sensors and more recently as scaffolds for tissueand organ regeneration. Scaffolds that can transmit electrical impulses have been shown to be beneficial inregeneration of tissues like muscle and nerve that are electroactive in nature. Most cellular events and cellfunctions are regulated by ion movement, and their imbalance is the cause of several diseases. We report synthesisand characterization of sulfonated polymers of poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA), poly(etherether ketone) (PEEK), poly(ether sulfone) (PES) and poly(phenylene oxide) (PPO) and evaluate their potential for tis-sue regeneration. The ionic conductive property stems from the presence of sulfonic groups on the polymer back-bone. The structure of the polymer was confirmed using Fourier Transform Infrared Spectroscopy and membranehydrophicity was determined by water contact angle measurement. The electrical conductivity of these sulfonatedmembranes was found to be 53.55, 35.39 and 29.51mS/cm for SPPO, SPEEK and SPMVEMA, respectively. Theconductivity was directly proportional to the sulfonic acid content on the polymer backbone. The ionic membranesnamely SPPO, SPEEK and SPMVEMA demonstrated superior cell adhesion properties (~7–10 fold higher) than cellsseeded onto tissue culture polystyrene. The sulfonated membranes exhibited static water contact angle in the rangeof 70–76°. The membranes supported the proliferation of human skin fibroblasts over 14days in culture asevidencedbyconfocaland electronmicroscopyimaging.Theionicmaterials reportedinthisstudymayserveasscaf-folds for a variety of tissue healing and drug delivery applications. Copyright © 2014 John Wiley & Sons, Ltd.Keywords: Electrically conducting polymers; Ionic conductance; Nerve regeneration; Muscle Regeneration; Biocompatibility

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.

Polymers derived from plant (polysaccharides) and animal (proteins) kingdoms have been widely used for a variety of biomedical applications including drug delivery and tissue regeneration. These polymers due to their biochemical similarity with human extracellular matrix components are readily recognized and accepted by the body. Natural polymers inherit numerous advantages including natural abundance, relative ease of isolation, and room for chemical modification to meet varying technological needs. In addition, these polymers undergo enzymatic and/or hydrolytic degradation in biologic environments into non-toxic degradation byproducts. Polysaccharides (carbohydrates) are often isolated and purified from renewable sources including plants, animals, and microorganisms. Majority of these polymers are found in the extracellular matrix components of organisms and participate in inter and intracellular cell signaling and contribute to their growth. All these features offer polysaccharide-based biomaterials much desired biological recognition, biocompatibility, and bioactivity. In spite of many merits as biomaterials, these polysaccharides suffer from drawbacks including variations in material properties based on source, microbial contamination, uncontrolled water uptake, poor mechanical strength, and unpredictable degradation patterns. These inconsistencies have limited the usage of polysaccharides and biomedical application related technology development. Many of these polysaccharides have been chemically modified to achieve consistent physicochemical properties including mechanical stability, degradation, and bioactivity and processed into microparticles, hydrogels, and 3D porous structures for tissue regeneration applications. Presence of multiple functionalities on the polymer backbone allows easy structure modifications for the required application. The current article focuses on the application of polysaccharide-based materials in regenerative engineering and delivery. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in-growth in regenerative medicine. To allow tissue in-growth and nutrient transport, traditional three-dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4-phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures revealed macropores (10-100 μm) between spheres as well as micro- and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82-87% porosity. Cell infiltration and collagen tissue in-growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three-stage degradation mechanism. The robust tissue in-growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation.

Polyphosphazene-polyester blends are attractive materials for bone tissue engineering applications due to their controllable degradation pattern with non-toxic and neutral pH degradation products. In our ongoing quest for an ideal completely miscible polyphosphazene-polyester blend system, we report synthesis and characterization of a mixed-substituent biodegradable polyphosphazene poly[(glycine ethyl glycinato)(1)(phenyl phenoxy)(1)phosphazene] (PNGEG/PhPh) and its blends with a polyester. Two dipeptide-based blends namely 25:75 (Matrix1) and 50:50 (Matrix2) were produced at two different weight ratios of PNGEG/PhPh to poly(lactic acid-glycolic acid) (PLAGA). Blend miscibility was confirmed by differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Both blends resulted in higher tensile modulus and strength than the polyester. The blends showed a degradation rate in the order of Matrix2

Biodegradable polymeric scaffolds are being investigated as scaffolding materials for use in regenerative medicine. While the in vivo evaluation of various three-dimensional (3D), porous, biodegradable polymeric scaffolds has been reported, most studies are ≤3 months in duration, which is typically prior to bulk polymer degradation, a critical event that may initiate an inflammatory response and inhibit tissue formation. Here, a 6 month in vitro degradation and corresponding in vivo studies that characterized scaffold changes during complete degradation of an amorphous, 3D poly(lactide-co-glycolide) (3D-PLAGA) scaffold and near-complete degradation of a semi-crystalline 3D-PLAGA scaffold are reported. Using sintered microsphere matrix technology, constructs were fabricated in a tubular shape, with the longitudinal axis void and a median pore size that mimicked the architecture of native bone. Long-term quantitative measurements of molecular weight, mechanical properties, and porosity provided a basis for theorization of the scaffold degradation process. Following implantation in a critical size ulnar defect model, histological analysis and quantitative microCT indicated early solubilization of the semi-crystalline polymer created an acidic microenvironment that inhibited mineralized tissue formation. Thus, the use of amorphous over semi-crystalline PLAGA materials is advocated for applications in regenerative medicine.

The nontoxic, neutral degradation products of amino acid ester polyphosphazenes make them ideal candidates for in vivo orthopedic applications. The quest for new osteocompatible materials for load bearing tissue engineering applications has led us to investigate mechanically competent amino acid ester substituted polyphosphazenes. In this study, we have synthesized three biodegradable polyphosphazenes substituted with side groups, namely, leucine, valine, and phenylalanine ethyl esters. Of these polymers, the phenylalanine ethyl ester substituted polyphosphazene showed the highest glass transition temperature (41.6 degrees C) and, hence, was chosen as a candidate material for forming composite microspheres with 100 nm sized hydroxyapatite (nHAp). The fabricated composite microspheres were sintered into a three-dimensional (3-D) porous scaffold by adopting a dynamic solvent sintering approach. The composite microsphere scaffolds showed compressive moduli of 46-81 MPa with mean pore diameters in the range of 86-145 microm. The 3-D polyphosphazene-nHAp composite microsphere scaffolds showed good osteoblast cell adhesion, proliferation, and alkaline phosphatase expression and are potential suitors for bone tissue engineering applications.

Nanostructures in the form of tubes, wires, crystals, rods, spheres, and fibers have been fabricated and assembled into various macrostructures for a variety of high technology applications. Nanofeatures impart several amazing properties to these macrostructures including high surface area, surface functionality, and superior mechanical, optical, electrical, and magnetic properties over the parent bulk material. Polymeric nanofibers in the form of nonwoven cloth, membrane, braids and tubes are extensively used for daily needs, and in addition used as filters, protective clothing, and for a variety of industrial and biomedical applications. Electrospinning or electrostatic spinning has emerged as a very popular technique to fabricate polymeric nanofiber matrices. More than 100 different polymers of natural, synthetic origin, their blends and composites have been electrospun into different three dimensional (3-D) macrostructures. Electrospinning provides opportunities to manipulate and control surface area, fiber diameter, porosity and pore size of nanofiber matrices. These nanofiber matrices closely mimic the structure of extracellular matrix (ECM) and influence cellular activities both in vitro and in vivo. Nanofiber macrostructures have been used as a vehicle to deliver therapeutic agents, as scaffolds for engineering various tissues and also serve as an integrated part of biomedical implants. Present review will cover some of the recent important patents that use electrospun nanofiber matrices for various biomedical 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.

The need and the growing interest in polymers as biomaterials have led to the synthesis of new polymers with a variety of physico-chemical properties. Biomedical application of such materials not only depends on their physical properties but also on biocompatibility and biodegradability. Polyphosphazenes are a family of ‘hybrid inorganic–organic polymers’ with inorganic elements in the backbone and organic side-groups. The polyphosphazenes constitute a family of greatly diverse performance materials with a broad spectrum of properties. The present review focuses on the biodegradable polyphosphazenes, their biocompatibility, and degradation behavior both in vitro and in vivo. This review also covers the use of biodegradable polyphosphazenes as controlled release devices.

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.

Electrospinning is a technique to generate submicron-to nanometer-scale bers from polymer solutions or melts. It is also known as electrostatic spinning, that has some characteristics common with electrospraying and the traditional ber drawing process. Electrospinning is a simple and facile technique to produce nonwoven, interconnectedCONTENTS7.1 Introduction 229 7.2 Electrospinning: Basics and Instrumentation 230

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.