Nesrin Hasirci | Middle East Technical University (original) (raw)
Papers by Nesrin Hasirci
In this study, a novel 5-layered meniscus scaffold, constituted of 3 different collagen-based foa... more In this study, a novel 5-layered meniscus scaffold, constituted of 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats, was designed to mimic the mechanical and physical properties of the natural meniscus. The top layer was a collagen-chondroitin sulfate-hyaluronic acid (Coll-CS-HA) foam. The middle and bottom layers were collagen foams which had different porosities and compressive properties. The aligned mats in between the foams were a blend of collagen and poly(L-lactic acid-co-glycolic acid). For the 5-layered construct, the compressive, tensile and shear moduli were 445 KPa, 3 MPa and 194 KPa, respectively. In dry state, the construct possessed higher compressive and shear properties than the natural tissue but the tensile properties were much lower. The mechanical properties are expected to be improved when the cells are seeded on the scaffold by their secretion of collagen and GAG.
Keywords: 5-LAYERED 3D CONSTRUCT; COLLAGEN FOAMS; MECHANICAL PROPERTIES; MENISCUS REPLACEMENT
Journal of materials science. Materials in medicine, 2014
Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we ... more Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we believe tissue engineering could be a viable solution. In this study, a three dimensional, collagen-based meniscus substitute was prepared by tissue engineering using human fibrochondrocytes and a collagen based-scaffold. This construct was made with 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats. The top layer was made of collagen type I–chondroitin sulfate–hyaluronic acid (Coll–CS–HA), and the middle and the bottom layers were made of only collagen type I with different porosities and thus with different mechanical properties. The mats of aligned fibers were a blend of collagen type I and poly(l-lactic acid-co-glycolic acid) (PLGA). After seeding with human fibrochondrocytes, cell attachment, proliferation, and production of extracellular matrix and glucoseaminoglycan were studied. Cell seeding had a positive effect on the compressive properties of foams and the 3D construct. The 3D construct with all its 5 layers had better mechanical properties than the individual foams.
Polymer Composites, 2012
ABSTRACT In this study, novel composite bone fillers with microspherical shape, biodegradable pro... more ABSTRACT In this study, novel composite bone fillers with microspherical shape, biodegradable property, and antibacterial effect were designed and prepared. Various fillers with different β-tricalcium phosphate (β-TCP)/gelatin (G)/glutaraldeyde (GA) compositions were loaded with a model antibiotic, gentamicin. The effect of composition and preparation conditions on the release of gentamicin was investigated in in vitro conditions. Complete release were observed in 12 h for pure β-TCP powder, and this period was extended up to 96 h as the gelatin content increased in the microspheres. Morphological and chemical structures of the microspheres, before and after the release studies, were investigated by scanning electron microscopy and Fourier transform infrared, respectively. Antibacterial activities were examined against Escherichia coli by using disc diffusion method and promising results were obtained. It is proposed that these novel β-TCP/G/GA microspheres can be applied locally to prevent and/or eliminate infection that might occur around a defected region of hard tissue and supports the healing process. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Journal of Biomaterials and Tissue Engineering, 2015
ABSTRACT Infected wounds are global healthcare problems since they can lead to dysfunctioning in ... more ABSTRACT Infected wounds are global healthcare problems since they can lead to dysfunctioning in organs and even result in death in severe cases. In this study, antibacterial wound dressings were prepared to prevent possible infection at the damaged host region. For this purpose, three natural polymers namely heparin, chitosan and alginate were used as anionic, cationic and sulfated polysaccharides, respectively, due to their versatile properties as being nontoxic, biocompatible, biodegradable and antibacterial. Heparin/chitosan/alginate based complex polyelectrolyte scaffolds containing different amounts of heparin were prepared by freeze drying technique. The effects of calcium chloride, which is used as crosslinker for alginate, on the stability of scaffolds were tested. Presence of functional groups and morphological structures of the scaffolds were examined in detail by using FTIR, XPS and SEM. Antibacterial activities against Staphylococcus epidermidis (S. epidermidis) were investigated under in vitro conditions. Presence and the amount of heparin in the scaffolds significantly enhanced the antibacterial activities. The results demonstrated that heparin/chitosan/alginate polyelectrolyte scaffolds have very high potential to be used as therapeutic wound dressings.
Journal of Polymer Research, 2013
... While nsHA added pure chitoan films showed higher cell number with respect to chitosan films;... more ... While nsHA added pure chitoan films showed higher cell number with respect to chitosan films; on the contrry, chitosan-gelatin ... 1,2]. Bu çalışma farklı oranlarda kitosan (C), jelatin (G) ve katılaştırılmamış hidroksiapatit (nsHA) kullanarak iki-boyutlu (film) yapıların hazırlanmasını ...
Key Engineering Materials, 2011
ABSTRACT
Journal of Materials Science: Materials in Medicine, 2010
The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo cond... more The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(e-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation on random scaffolds was significantly higher compared to the oriented ones. Delivery of BMP-2 alone suppressed MSC proliferation and increased the ALP activity to a higher level than that with BMP-7 delivery. Proliferation rate was suppressed the most by the sequential delivery of the two growth factors from the random scaffold on which the ALP activity was the highest. Results indicated the distinct effect of scaffold architecture and the mode of growth factor delivery on the proliferation and osteogenic differentiation of MSCs, enabling us to design multifunctional scaffolds capable of controlling bone healing.
Self-curing acrylic cements, consisting mainly of polymethylmethacrylate (PMMA), are widely used ... more Self-curing acrylic cements, consisting mainly of polymethylmethacrylate (PMMA), are widely used in dentistry and orthopedic surgery. One of the major side effects of the standard PMMA application is tissue necrosis at the bone-cement interface due to the rise of temperature during the polymerization reaction. This may also lead to aseptic loosening over time. Therefore, intense research is being carried out
Journal of Applied Polymer Science, 1995
Journal of Bioactive and Compatible Polymers
Several polymers derived from natural materials are effective for tissue engineering or drug deli... more Several polymers derived from natural materials are effective for tissue engineering or drug delivery applications, due to specific properties, such as biocompatibility, biodegradability, and structural activity. Their blood compatibility needs to be carefully evaluated to avoid thrombosis and other material-related adverse events in the hematic environment. We compared the surface properties and blood compatibility of protein and polysaccharide polymers, including fibroin, gelatin, and chitosan. Both fibroin and chitosan showed good hemocompatibility, with low platelet adhesion and spreading. Chitosan induced strong interactions with plasma proteins, especially with albumin. It was hypothesized that surface passivation by albumin inhibited the adsorption of other procoagulant and proadhesive proteins on chitosan and fibroin films, which limited platelet spreading. However, the significant and rapid polymer swelling encouraged protein entrapment within the soft, gelatin films, induc...
Journal of Tissue Engineering and Regenerative Medicine
This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engin... more This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engineering scaffolds. Structures presenting homogeneously distributed pores of size 100 and 200 µm were fabricated through layer-by-layer deposition of filaments of poly(D,L-lactic acid) (PDLLA) prepared from dichloromethane/dimethylformamide solutions. Rheological tests on the solution and molecular weight distributions of PDLLA, solvent cast films and microfabricated scaffolds were performed to determine which material conditions are optimal for the microfabricated system and to identify any possible material modification induced by the process. In vitro qualitative preliminary cell culture studies were conducted using MG63 osteoblast cell lines after assuring the non-cytotoxicity of the scaffold material by the lactate dehydrogenase in vitro toxicology assay; biological evaluations were initially performed using scaffolds with the smaller (100 µm) pore size. Scanning electron microscopy i...
Journal of Drug Targeting, 2005
The objective of the present study was to prepare nanoparticles composed of poly(γ-glutamic acid)... more The objective of the present study was to prepare nanoparticles composed of poly(γ-glutamic acid) (γ-PGA) and l-phenylalanine ethylester (l-PAE) in order to evaluate the possibility of using these nanoparticles as protein carriers. Novel amphiphilic graft copolymers composed of γ-PGA as the hydrophilic backbone and l-PAE as the hydrophobic segment were successfully synthesized by grafting l-PAE to γ-PGA using water-soluble carbodiimide
Urological Research, 2004
Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesi... more Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For
Resources Conservation and Recycling, 1996
Increasing attention is being directed to reducing the amount of pesticides, herbicides, and othe... more Increasing attention is being directed to reducing the amount of pesticides, herbicides, and other biologically active agents used in modern agricultural crop management. One method for reducing the amount of such agents, while still maintaining effectiveness, is to encapsulate or otherwise incorporate the active agent into some from of plastic. Such ‘filled’ plastics, usually prepared by certain techniques for standard
Central European Journal of Medicine, 2009
Abstract: Incisional hernias and abdominal-wall defects consume large amounts of healthcare resou... more Abstract: Incisional hernias and abdominal-wall defects consume large amounts of healthcare resources. Use of mesh is effective in treatment of these disorders and can decrease the rate of recurrence. This experimental study focused on the safety of mesh use in the set-ting ...
Urology, 2010
To evaluate the effects of the local release of fibroblast growth factor (FGF), insulin-like grow... more To evaluate the effects of the local release of fibroblast growth factor (FGF), insulin-like growth factor (IGF), and growth hormone (GH) on a germ cell population of ipsilateral undescended and contralateral descended testes of rats with a surgically created unilateral abdominal testis for 12 weeks and after the application of growth factors after orchidopexy. Forty 4-week old male Wistar albino rats were divided into 5 groups as follows: group 1, sham; group 2, gelatin; group 3, FGF; group 4, IGF; and group 5, GH. In the sham group, the right testis was exposed and sutured with 5-0 silk sutures. In groups 2-5, a right intra-abdominal testis was surgically created. After 12 weeks, orchidopexy was performed, and 1 cm(2) gelatin films were sutured to the right testes, either unloaded (group 2), or containing 2.5 microg FGF (group 3), 5 microg IGF (group 4), or 5 microg GH (group 5). After 30 days, both testes were removed for histopathologic investigation and DNA flow cytometry. The mean seminiferous tubular diameters (MSTDs), mean testicular biopsy scores (MTBSs), and percentages of haploid (1n) cells were calculated. Ipsilateral MSTD and MTBS significantly decreased in the gelatin and FGF groups compared with the sham, IGF, and GH groups. Contralateral MSTDs and MTBSs did not differ among groups. The haploid cell percentage significantly decreased in the ipsilateral and contralateral testes of the gelatin group compared with the sham, FGF, IGF, and GH groups. Local release of IGF and GH resulted in the preservation of germ cell histology in the ipsilateral testes of rats with a surgically created unilateral undescended testis for 12 weeks and after orchidopexy. The administration of IGF, GH, and FGF increased the haploid germ cell population in both ipsilateral undescended and contralateral descended testes.
British Polymer Journal, 1990
Polyurethane films were prepared using diphenylmethanediisocyanate [MDI] or hexamethylenediisocya... more Polyurethane films were prepared using diphenylmethanediisocyanate [MDI] or hexamethylenediisocyanate [HDI] and poly(propylene-ethy1ene) glycol, in order to test them as biomedical materials specifically for use as skin grafts. Other ingredients such as catalysts, chain extenders, solvents, etc., where not used in order to obtain medical purity.
In this study, a novel 5-layered meniscus scaffold, constituted of 3 different collagen-based foa... more In this study, a novel 5-layered meniscus scaffold, constituted of 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats, was designed to mimic the mechanical and physical properties of the natural meniscus. The top layer was a collagen-chondroitin sulfate-hyaluronic acid (Coll-CS-HA) foam. The middle and bottom layers were collagen foams which had different porosities and compressive properties. The aligned mats in between the foams were a blend of collagen and poly(L-lactic acid-co-glycolic acid). For the 5-layered construct, the compressive, tensile and shear moduli were 445 KPa, 3 MPa and 194 KPa, respectively. In dry state, the construct possessed higher compressive and shear properties than the natural tissue but the tensile properties were much lower. The mechanical properties are expected to be improved when the cells are seeded on the scaffold by their secretion of collagen and GAG.
Keywords: 5-LAYERED 3D CONSTRUCT; COLLAGEN FOAMS; MECHANICAL PROPERTIES; MENISCUS REPLACEMENT
Journal of materials science. Materials in medicine, 2014
Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we ... more Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we believe tissue engineering could be a viable solution. In this study, a three dimensional, collagen-based meniscus substitute was prepared by tissue engineering using human fibrochondrocytes and a collagen based-scaffold. This construct was made with 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats. The top layer was made of collagen type I–chondroitin sulfate–hyaluronic acid (Coll–CS–HA), and the middle and the bottom layers were made of only collagen type I with different porosities and thus with different mechanical properties. The mats of aligned fibers were a blend of collagen type I and poly(l-lactic acid-co-glycolic acid) (PLGA). After seeding with human fibrochondrocytes, cell attachment, proliferation, and production of extracellular matrix and glucoseaminoglycan were studied. Cell seeding had a positive effect on the compressive properties of foams and the 3D construct. The 3D construct with all its 5 layers had better mechanical properties than the individual foams.
Polymer Composites, 2012
ABSTRACT In this study, novel composite bone fillers with microspherical shape, biodegradable pro... more ABSTRACT In this study, novel composite bone fillers with microspherical shape, biodegradable property, and antibacterial effect were designed and prepared. Various fillers with different β-tricalcium phosphate (β-TCP)/gelatin (G)/glutaraldeyde (GA) compositions were loaded with a model antibiotic, gentamicin. The effect of composition and preparation conditions on the release of gentamicin was investigated in in vitro conditions. Complete release were observed in 12 h for pure β-TCP powder, and this period was extended up to 96 h as the gelatin content increased in the microspheres. Morphological and chemical structures of the microspheres, before and after the release studies, were investigated by scanning electron microscopy and Fourier transform infrared, respectively. Antibacterial activities were examined against Escherichia coli by using disc diffusion method and promising results were obtained. It is proposed that these novel β-TCP/G/GA microspheres can be applied locally to prevent and/or eliminate infection that might occur around a defected region of hard tissue and supports the healing process. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Journal of Biomaterials and Tissue Engineering, 2015
ABSTRACT Infected wounds are global healthcare problems since they can lead to dysfunctioning in ... more ABSTRACT Infected wounds are global healthcare problems since they can lead to dysfunctioning in organs and even result in death in severe cases. In this study, antibacterial wound dressings were prepared to prevent possible infection at the damaged host region. For this purpose, three natural polymers namely heparin, chitosan and alginate were used as anionic, cationic and sulfated polysaccharides, respectively, due to their versatile properties as being nontoxic, biocompatible, biodegradable and antibacterial. Heparin/chitosan/alginate based complex polyelectrolyte scaffolds containing different amounts of heparin were prepared by freeze drying technique. The effects of calcium chloride, which is used as crosslinker for alginate, on the stability of scaffolds were tested. Presence of functional groups and morphological structures of the scaffolds were examined in detail by using FTIR, XPS and SEM. Antibacterial activities against Staphylococcus epidermidis (S. epidermidis) were investigated under in vitro conditions. Presence and the amount of heparin in the scaffolds significantly enhanced the antibacterial activities. The results demonstrated that heparin/chitosan/alginate polyelectrolyte scaffolds have very high potential to be used as therapeutic wound dressings.
Journal of Polymer Research, 2013
... While nsHA added pure chitoan films showed higher cell number with respect to chitosan films;... more ... While nsHA added pure chitoan films showed higher cell number with respect to chitosan films; on the contrry, chitosan-gelatin ... 1,2]. Bu çalışma farklı oranlarda kitosan (C), jelatin (G) ve katılaştırılmamış hidroksiapatit (nsHA) kullanarak iki-boyutlu (film) yapıların hazırlanmasını ...
Key Engineering Materials, 2011
ABSTRACT
Journal of Materials Science: Materials in Medicine, 2010
The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo cond... more The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(e-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation on random scaffolds was significantly higher compared to the oriented ones. Delivery of BMP-2 alone suppressed MSC proliferation and increased the ALP activity to a higher level than that with BMP-7 delivery. Proliferation rate was suppressed the most by the sequential delivery of the two growth factors from the random scaffold on which the ALP activity was the highest. Results indicated the distinct effect of scaffold architecture and the mode of growth factor delivery on the proliferation and osteogenic differentiation of MSCs, enabling us to design multifunctional scaffolds capable of controlling bone healing.
Self-curing acrylic cements, consisting mainly of polymethylmethacrylate (PMMA), are widely used ... more Self-curing acrylic cements, consisting mainly of polymethylmethacrylate (PMMA), are widely used in dentistry and orthopedic surgery. One of the major side effects of the standard PMMA application is tissue necrosis at the bone-cement interface due to the rise of temperature during the polymerization reaction. This may also lead to aseptic loosening over time. Therefore, intense research is being carried out
Journal of Applied Polymer Science, 1995
Journal of Bioactive and Compatible Polymers
Several polymers derived from natural materials are effective for tissue engineering or drug deli... more Several polymers derived from natural materials are effective for tissue engineering or drug delivery applications, due to specific properties, such as biocompatibility, biodegradability, and structural activity. Their blood compatibility needs to be carefully evaluated to avoid thrombosis and other material-related adverse events in the hematic environment. We compared the surface properties and blood compatibility of protein and polysaccharide polymers, including fibroin, gelatin, and chitosan. Both fibroin and chitosan showed good hemocompatibility, with low platelet adhesion and spreading. Chitosan induced strong interactions with plasma proteins, especially with albumin. It was hypothesized that surface passivation by albumin inhibited the adsorption of other procoagulant and proadhesive proteins on chitosan and fibroin films, which limited platelet spreading. However, the significant and rapid polymer swelling encouraged protein entrapment within the soft, gelatin films, induc...
Journal of Tissue Engineering and Regenerative Medicine
This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engin... more This study aimed to comprehend the potentialities of the microfabrication to produce tissue-engineering scaffolds. Structures presenting homogeneously distributed pores of size 100 and 200 µm were fabricated through layer-by-layer deposition of filaments of poly(D,L-lactic acid) (PDLLA) prepared from dichloromethane/dimethylformamide solutions. Rheological tests on the solution and molecular weight distributions of PDLLA, solvent cast films and microfabricated scaffolds were performed to determine which material conditions are optimal for the microfabricated system and to identify any possible material modification induced by the process. In vitro qualitative preliminary cell culture studies were conducted using MG63 osteoblast cell lines after assuring the non-cytotoxicity of the scaffold material by the lactate dehydrogenase in vitro toxicology assay; biological evaluations were initially performed using scaffolds with the smaller (100 µm) pore size. Scanning electron microscopy i...
Journal of Drug Targeting, 2005
The objective of the present study was to prepare nanoparticles composed of poly(γ-glutamic acid)... more The objective of the present study was to prepare nanoparticles composed of poly(γ-glutamic acid) (γ-PGA) and l-phenylalanine ethylester (l-PAE) in order to evaluate the possibility of using these nanoparticles as protein carriers. Novel amphiphilic graft copolymers composed of γ-PGA as the hydrophilic backbone and l-PAE as the hydrophobic segment were successfully synthesized by grafting l-PAE to γ-PGA using water-soluble carbodiimide
Urological Research, 2004
Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesi... more Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For
Resources Conservation and Recycling, 1996
Increasing attention is being directed to reducing the amount of pesticides, herbicides, and othe... more Increasing attention is being directed to reducing the amount of pesticides, herbicides, and other biologically active agents used in modern agricultural crop management. One method for reducing the amount of such agents, while still maintaining effectiveness, is to encapsulate or otherwise incorporate the active agent into some from of plastic. Such ‘filled’ plastics, usually prepared by certain techniques for standard
Central European Journal of Medicine, 2009
Abstract: Incisional hernias and abdominal-wall defects consume large amounts of healthcare resou... more Abstract: Incisional hernias and abdominal-wall defects consume large amounts of healthcare resources. Use of mesh is effective in treatment of these disorders and can decrease the rate of recurrence. This experimental study focused on the safety of mesh use in the set-ting ...
Urology, 2010
To evaluate the effects of the local release of fibroblast growth factor (FGF), insulin-like grow... more To evaluate the effects of the local release of fibroblast growth factor (FGF), insulin-like growth factor (IGF), and growth hormone (GH) on a germ cell population of ipsilateral undescended and contralateral descended testes of rats with a surgically created unilateral abdominal testis for 12 weeks and after the application of growth factors after orchidopexy. Forty 4-week old male Wistar albino rats were divided into 5 groups as follows: group 1, sham; group 2, gelatin; group 3, FGF; group 4, IGF; and group 5, GH. In the sham group, the right testis was exposed and sutured with 5-0 silk sutures. In groups 2-5, a right intra-abdominal testis was surgically created. After 12 weeks, orchidopexy was performed, and 1 cm(2) gelatin films were sutured to the right testes, either unloaded (group 2), or containing 2.5 microg FGF (group 3), 5 microg IGF (group 4), or 5 microg GH (group 5). After 30 days, both testes were removed for histopathologic investigation and DNA flow cytometry. The mean seminiferous tubular diameters (MSTDs), mean testicular biopsy scores (MTBSs), and percentages of haploid (1n) cells were calculated. Ipsilateral MSTD and MTBS significantly decreased in the gelatin and FGF groups compared with the sham, IGF, and GH groups. Contralateral MSTDs and MTBSs did not differ among groups. The haploid cell percentage significantly decreased in the ipsilateral and contralateral testes of the gelatin group compared with the sham, FGF, IGF, and GH groups. Local release of IGF and GH resulted in the preservation of germ cell histology in the ipsilateral testes of rats with a surgically created unilateral undescended testis for 12 weeks and after orchidopexy. The administration of IGF, GH, and FGF increased the haploid germ cell population in both ipsilateral undescended and contralateral descended testes.
British Polymer Journal, 1990
Polyurethane films were prepared using diphenylmethanediisocyanate [MDI] or hexamethylenediisocya... more Polyurethane films were prepared using diphenylmethanediisocyanate [MDI] or hexamethylenediisocyanate [HDI] and poly(propylene-ethy1ene) glycol, in order to test them as biomedical materials specifically for use as skin grafts. Other ingredients such as catalysts, chain extenders, solvents, etc., where not used in order to obtain medical purity.