Sundararajan Madihally | Oklahoma State University (original) (raw)
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Papers by Sundararajan Madihally
Introduction: Polycaprolactone (PCL) is the biocompatible polyester which is explored in forming ... more Introduction: Polycaprolactone (PCL) is the biocompatible polyester which is explored in forming various medical devices, templates in tissue regeneration and drug delivery systems. Typically used halogenated hydrocarbon solvents such as Chloroform have been shown to generate a hydrophobic surface with smooth surface characteristics. We have discovered that PCL can be dissolved in glacial acetic acid (AA) which allows spontaneous aggregation of PCL upon contact with water. The aim of this study was to compare the characteristics of self assembled matrices to those formed using chloroform. Formed matrices were evaluated for surface characteristics, tensile properties, cellular interactions and effect of mixing gelatin, chitosan, and Dextran sulfate in the same solution. Materials and Methods: 10% (wt/v) PCL (80kDa MW) solution was prepared in glacial acetic acid, and the same MW PCL solution was prepared in chloroform to compare the effect of solvent. PCL matrices were made in 5 cm d...
Journal of Biomedical Materials Research Part A, 2006
This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid (PLGA) blend ma... more This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid (PLGA) blend matrices using controlled-rate freezing and lyophilization technique (CRFLT). An emulsion system was used in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), a cellular component, as a stabilizer. Blended scaffolds showed an open pore morphology and homogenous interdispersion of PLGA and chitosan. Forming emulsions after dissolving PLGA in chloroform, benzene, or methylene chloride indicated better emulsion stability with benzene and chloroform. Scaffolds formed by freezing at À20, À78, and À1968C from these emulsions showed significant influence of the solvent and freezing temperature on the microarchitecture of the scaffold. By controlling the concentration of chitosan, scaffolds with greater than 90% porosity were attained. Since the two polymers degrade by different mechanisms, formed scaffolds were analyzed for degradation characteristics for 4 weeks in presence of 10 mg/L lysozyme. These results showed no significant difference in the weight loss and dimension changes, as all scaffolds showed significant (a) weight loss and (b) nearly 60% reduction in volume. Further, pH of the incubation media decreased in all the samples. When cellular activity of green fluorescence proteintransfected smooth muscle cells was analyzed, no apparent cytotoxicity was observed. However, the cell spreading area decreased. In summary, these results show promising potential in tissue engineering and drug delivery applications.
Biomaterials, 2006
Glycosaminoglycans (GAGs) have been explored for regenerating various tissues due to their involv... more Glycosaminoglycans (GAGs) have been explored for regenerating various tissues due to their involvement in diverse bioregulatory activity. However, understanding their influence on cell colonization in three-dimension (3-D) has been difficult due to variation in their molecular weight, degree of sulfation, and lack of in vitro models. This research focused on developing an in vitro model and evaluating the influence of MW (5, 10, and 500 kDa) of negatively charged dextran sulfate (DS), a semisynthetic GAG analog, on cell colonization. DS was combined with chitosan, a positively charged polymer in solution and porous 3-D matrices were formed inside 24-well plates using controlled rate freezing and lyophilization technique by two schemes: (i) chitosan structures were formed and then allowed to react with DS; (ii) DS was reacted with chitosan in solution and then matrices were formed. Scanning electron microscopy analysis showed that forming matrices after reacting DS with chitosan was more suitable for tissue regeneration. Analysis for the quantity and stability of DS by toluidine blue assay indicated significant presence of DS in the 3-D matrices even after seven days of incubation in phosphate buffered saline solution. Matrices formed by reacting 4% 5 kDa, 2% 10 kDa and 1% 500 kDa DS solution with chitosan had optimum porosity and mechanical stability. Next, 25,000 fibroblasts per matrix were seeded onto 3-D matrices and analyzed for proliferation by MTT-formazan assay, cytoskeletal organization by actin staining, and histological analysis by H/E staining. These results showed that cell growth was better on low MW containing 2-D membranes but high MW DS containing 3-D matrix supported cell growth similar to chitosan. Also, cells showed peripheral actin distribution in 3-D matrices. Analysis of fibronectin binding by ELISA showed negligible binding to all the DS-containing matrices, unlike chitosan. In summary, results show cell colonization on negatively charged matrices, similar to chitosan.
Most biological tissues and scaffolds used in tissue regeneration display time-dependent and load... more Most biological tissues and scaffolds used in tissue regeneration display time-dependent and load-history-dependent mechanical behavior. Soft tissues such as muscles, tendons, ligaments, fascia, nerves, fibrous tissues, fat, blood vessels, and synovial membranes display nonlinear material behavior and are found to exhibit viscoelastic character. Further, porous polymeric biodegradable structures utilized in tissue regeneration also show viscoelastic behavior. A number of models have been developed to assess the nonlinear viscoelastic behavior of soft materials. The most common phenomenological model has been the Quasi Linear Viscoelastic (QLV) model, introduced by Fung and later modified by many others according to comply with specific test or material requirements. The QLV theory assumes that the stress relaxation behavior of soft tissues can be expressed as a convolution integral of a strain independent reduced relaxation function and a nonlinear instantaneous stress function resu...
Determining parameter values of the Quasi Linear Viscoelastic (QLV) model is important for unders... more Determining parameter values of the Quasi Linear Viscoelastic (QLV) model is important for understanding the nonlinear viscoelastic behavior of soft biological materials. QLV parameters are evaluated by nonlinear regression of the model to data; however, currently used methodologies are confounded by multiple optima and other surface features that trap or divert searches. The search for the global optimum requires substantial human intervention. Further, the right values for stopping criteria thresholds on the objective function and decision variables (model parameters), or their iteration-to-iteration changes depends on a priori knowledge of the system. As a result, the coefficient values from nonlinear regression strongly depend on the initial guesses for parameters values and stopping criteria thresholds, and may not determine the global minimum, thus providing incorrect parametric values. This work describes two novel techniques to avoid these problems. First, regression is init...
Electrospinning technique in textile technology has recently emerged as a novel technique for tis... more Electrospinning technique in textile technology has recently emerged as a novel technique for tissue regeneration because it is versatile and relatively economical to manufacture nanofibers similar to natural extracellular membrane. A major problem in electrospinning technique is the lack of generating structural features necessary for building 3D tissue. Polymeric structures of electrospun fibers have tiny pores compared to human cells, and do not allow cells to infiltrate into the layers below the surface. In this study, we describe a novel fabrication method of electrospun fiber made of polycaprolactone (PCL) and gelatin with an innovative collector to fabricate the thin layer of fibers with large pore sizes. The novelty of this technique is the collector which allows the thin layer of nano or micro sized fibers with large pore size very suitable for tissue regeneration. Also, novel deposit processes (sequential and simultaneous deposit) facilitate formation of composite structur...
International Journal of Pharmaceutics
Enhancing transdermal delivery of insulin using chemical penetration enhancers (CPEs) has several... more Enhancing transdermal delivery of insulin using chemical penetration enhancers (CPEs) has several advantages over other non-traditional methods; however, lack of suitable predictive models, make experimentation the only alternative for discovering new CPEs. To address this limitation, a quantitative structure–property relationship (QSPR) model was developed, for predicting insulin permeation in the presence of CPEs. A virtual design algorithm that incorporates QSPR models for predicting CPE properties was used to identify 48 potential CPEs. Permeation experiments using Franz diffusion cells and resistance experiments were performed to quantify the effect of CPEs on insulin permeability and skin structure, respectively. Of the 48 CPEs, 35 were used for training and 13 were used for validation. In addition, 12 CPEs reported in literature were also included in the validation set. Differential evolution (DE) was coupled with artificial neural networks (ANNs) to develop the non-linear QS...
International Journal of Pharmaceutics
Using chemical penetration enhancers (CPEs), transdermal drug delivery (TDD) offers an alternativ... more Using chemical penetration enhancers (CPEs), transdermal drug delivery (TDD) offers an alternative route for insulin administration, wherein the CPEs reversibly reduce the barrier resistance of the skin. However, there is a lack of sufficient information concerning the effect of CPE chemical structure on insulin permeation. To address this limitation, we examined the effect of CPE functional groups on the permeation of insulin. A virtual design algorithm that incorporates quantitative structure–property relationship (QSPR) models for predicting the CPE properties was used to identify 43 potential CPEs. This set of CPEs was pre-screened using a resistance technique, and the 22 best CPEs were selected. Next, standard permeation experiments in Franz cells were performed to quantify insulin permeation.Our results indicate that specific functional groups are not directly responsible for enhanced insulin permeation. Rather, permeation enhancement is produced by molecules that exhibit posi...
Introduction: Polycaprolactone (PCL) is the biocompatible polyester which is explored in forming ... more Introduction: Polycaprolactone (PCL) is the biocompatible polyester which is explored in forming various medical devices, templates in tissue regeneration and drug delivery systems. Typically used halogenated hydrocarbon solvents such as Chloroform have been shown to generate a hydrophobic surface with smooth surface characteristics. We have discovered that PCL can be dissolved in glacial acetic acid (AA) which allows spontaneous aggregation of PCL upon contact with water. The aim of this study was to compare the characteristics of self assembled matrices to those formed using chloroform. Formed matrices were evaluated for surface characteristics, tensile properties, cellular interactions and effect of mixing gelatin, chitosan, and Dextran sulfate in the same solution. Materials and Methods: 10% (wt/v) PCL (80kDa MW) solution was prepared in glacial acetic acid, and the same MW PCL solution was prepared in chloroform to compare the effect of solvent. PCL matrices were made in 5 cm d...
Journal of Biomedical Materials Research Part A, 2006
This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid (PLGA) blend ma... more This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid (PLGA) blend matrices using controlled-rate freezing and lyophilization technique (CRFLT). An emulsion system was used in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), a cellular component, as a stabilizer. Blended scaffolds showed an open pore morphology and homogenous interdispersion of PLGA and chitosan. Forming emulsions after dissolving PLGA in chloroform, benzene, or methylene chloride indicated better emulsion stability with benzene and chloroform. Scaffolds formed by freezing at À20, À78, and À1968C from these emulsions showed significant influence of the solvent and freezing temperature on the microarchitecture of the scaffold. By controlling the concentration of chitosan, scaffolds with greater than 90% porosity were attained. Since the two polymers degrade by different mechanisms, formed scaffolds were analyzed for degradation characteristics for 4 weeks in presence of 10 mg/L lysozyme. These results showed no significant difference in the weight loss and dimension changes, as all scaffolds showed significant (a) weight loss and (b) nearly 60% reduction in volume. Further, pH of the incubation media decreased in all the samples. When cellular activity of green fluorescence proteintransfected smooth muscle cells was analyzed, no apparent cytotoxicity was observed. However, the cell spreading area decreased. In summary, these results show promising potential in tissue engineering and drug delivery applications.
Biomaterials, 2006
Glycosaminoglycans (GAGs) have been explored for regenerating various tissues due to their involv... more Glycosaminoglycans (GAGs) have been explored for regenerating various tissues due to their involvement in diverse bioregulatory activity. However, understanding their influence on cell colonization in three-dimension (3-D) has been difficult due to variation in their molecular weight, degree of sulfation, and lack of in vitro models. This research focused on developing an in vitro model and evaluating the influence of MW (5, 10, and 500 kDa) of negatively charged dextran sulfate (DS), a semisynthetic GAG analog, on cell colonization. DS was combined with chitosan, a positively charged polymer in solution and porous 3-D matrices were formed inside 24-well plates using controlled rate freezing and lyophilization technique by two schemes: (i) chitosan structures were formed and then allowed to react with DS; (ii) DS was reacted with chitosan in solution and then matrices were formed. Scanning electron microscopy analysis showed that forming matrices after reacting DS with chitosan was more suitable for tissue regeneration. Analysis for the quantity and stability of DS by toluidine blue assay indicated significant presence of DS in the 3-D matrices even after seven days of incubation in phosphate buffered saline solution. Matrices formed by reacting 4% 5 kDa, 2% 10 kDa and 1% 500 kDa DS solution with chitosan had optimum porosity and mechanical stability. Next, 25,000 fibroblasts per matrix were seeded onto 3-D matrices and analyzed for proliferation by MTT-formazan assay, cytoskeletal organization by actin staining, and histological analysis by H/E staining. These results showed that cell growth was better on low MW containing 2-D membranes but high MW DS containing 3-D matrix supported cell growth similar to chitosan. Also, cells showed peripheral actin distribution in 3-D matrices. Analysis of fibronectin binding by ELISA showed negligible binding to all the DS-containing matrices, unlike chitosan. In summary, results show cell colonization on negatively charged matrices, similar to chitosan.
Most biological tissues and scaffolds used in tissue regeneration display time-dependent and load... more Most biological tissues and scaffolds used in tissue regeneration display time-dependent and load-history-dependent mechanical behavior. Soft tissues such as muscles, tendons, ligaments, fascia, nerves, fibrous tissues, fat, blood vessels, and synovial membranes display nonlinear material behavior and are found to exhibit viscoelastic character. Further, porous polymeric biodegradable structures utilized in tissue regeneration also show viscoelastic behavior. A number of models have been developed to assess the nonlinear viscoelastic behavior of soft materials. The most common phenomenological model has been the Quasi Linear Viscoelastic (QLV) model, introduced by Fung and later modified by many others according to comply with specific test or material requirements. The QLV theory assumes that the stress relaxation behavior of soft tissues can be expressed as a convolution integral of a strain independent reduced relaxation function and a nonlinear instantaneous stress function resu...
Determining parameter values of the Quasi Linear Viscoelastic (QLV) model is important for unders... more Determining parameter values of the Quasi Linear Viscoelastic (QLV) model is important for understanding the nonlinear viscoelastic behavior of soft biological materials. QLV parameters are evaluated by nonlinear regression of the model to data; however, currently used methodologies are confounded by multiple optima and other surface features that trap or divert searches. The search for the global optimum requires substantial human intervention. Further, the right values for stopping criteria thresholds on the objective function and decision variables (model parameters), or their iteration-to-iteration changes depends on a priori knowledge of the system. As a result, the coefficient values from nonlinear regression strongly depend on the initial guesses for parameters values and stopping criteria thresholds, and may not determine the global minimum, thus providing incorrect parametric values. This work describes two novel techniques to avoid these problems. First, regression is init...
Electrospinning technique in textile technology has recently emerged as a novel technique for tis... more Electrospinning technique in textile technology has recently emerged as a novel technique for tissue regeneration because it is versatile and relatively economical to manufacture nanofibers similar to natural extracellular membrane. A major problem in electrospinning technique is the lack of generating structural features necessary for building 3D tissue. Polymeric structures of electrospun fibers have tiny pores compared to human cells, and do not allow cells to infiltrate into the layers below the surface. In this study, we describe a novel fabrication method of electrospun fiber made of polycaprolactone (PCL) and gelatin with an innovative collector to fabricate the thin layer of fibers with large pore sizes. The novelty of this technique is the collector which allows the thin layer of nano or micro sized fibers with large pore size very suitable for tissue regeneration. Also, novel deposit processes (sequential and simultaneous deposit) facilitate formation of composite structur...
International Journal of Pharmaceutics
Enhancing transdermal delivery of insulin using chemical penetration enhancers (CPEs) has several... more Enhancing transdermal delivery of insulin using chemical penetration enhancers (CPEs) has several advantages over other non-traditional methods; however, lack of suitable predictive models, make experimentation the only alternative for discovering new CPEs. To address this limitation, a quantitative structure–property relationship (QSPR) model was developed, for predicting insulin permeation in the presence of CPEs. A virtual design algorithm that incorporates QSPR models for predicting CPE properties was used to identify 48 potential CPEs. Permeation experiments using Franz diffusion cells and resistance experiments were performed to quantify the effect of CPEs on insulin permeability and skin structure, respectively. Of the 48 CPEs, 35 were used for training and 13 were used for validation. In addition, 12 CPEs reported in literature were also included in the validation set. Differential evolution (DE) was coupled with artificial neural networks (ANNs) to develop the non-linear QS...
International Journal of Pharmaceutics
Using chemical penetration enhancers (CPEs), transdermal drug delivery (TDD) offers an alternativ... more Using chemical penetration enhancers (CPEs), transdermal drug delivery (TDD) offers an alternative route for insulin administration, wherein the CPEs reversibly reduce the barrier resistance of the skin. However, there is a lack of sufficient information concerning the effect of CPE chemical structure on insulin permeation. To address this limitation, we examined the effect of CPE functional groups on the permeation of insulin. A virtual design algorithm that incorporates quantitative structure–property relationship (QSPR) models for predicting the CPE properties was used to identify 43 potential CPEs. This set of CPEs was pre-screened using a resistance technique, and the 22 best CPEs were selected. Next, standard permeation experiments in Franz cells were performed to quantify insulin permeation.Our results indicate that specific functional groups are not directly responsible for enhanced insulin permeation. Rather, permeation enhancement is produced by molecules that exhibit posi...