Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently used in a number of biomedical applications. A number of concerns have been raised over the toxicity of initiators commonly employed for the synthesis of PCL. Therefore, more biocompatible initiators have been studied. The biocompatibility of PCL, itself, is adequate; however, improved bioactivity is desirable for several applications. Copolymerisation, and incorporation of bioactive fillers can both be used as ways of enhancing the bioactivity of PCL. Therefore, the global objective of this project was to enhance the bioactivity of PCL by copolymerisation of PCL with poly(ethylene glycol) (PEG) using a biocompatible calcium-based initiator. This calcium-initiator was expected to leave potentially bioactive calcium-initiator residues in the synthesised copolymers. A study of the ring-opening polymerisation of epsilon-caprolactone (CL) in the presence of a poly(ethylene glycol) (PEG) / calcium hydride (CaH2) co-initiation system was performed. Polymerisation kinetics were monitored by following the degree of conversion of CL by Fourier transform-Raman (FT-Raman) spectroscopy and 1H nuclear magnetic resonance spectroscopy (NMR). Resultant PCL-b-PEG-b-PCL (PCL/PEG/PCL) triblock copolymers were analysed by NMR and gel permeation chromatography (GPC). The observed rates of polymerisation for the synthesis of PCL/PEG/PCL triblock copolymers using the PEG / CaH2 co-initiator were much lower than expected. 1H NMR and Raman microspectroscopy analysis showed that the concentration of the active calcium-PEG alkoxide was much lower than the initial feed concentration of PEG. Even so, the molecular weight of PCL/PEG/PCL triblock copolymers could be predicted from the CL : PEG feed ratio. This was found to be due to a fast reversible transfer process. Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of solutions containing acid digested, pure PCL/PEG/PCL copolymers showed calcium concentrations at equal to or greater than 77 % of the calcium feed concentration. These calcium-initiator residues were isolated and their structures confirmed by Fourier transform infrared-attenuated total reflectance spectroscopy (FTIR-ATR). They were found to be a mixture of calcium hydroxide (Ca(OH)2) and calcium carbonate (CaCO3). The effect of calcium-initiator residues on the in vitro mineralisation of PCL/PEG/PCL triblock copolymers, as well as the same effect on a model calcium-salt-doped PCL homopolymer system, was studied by immersion in simulated body fluid (SBF). In the model studied, PCL homopolymer was doped with low concentrations (0.2 - 2 w / w % Ca) of Ca(OH)2, or CaCO3. Results from the model study showed calcium phosphate (CaP) mineral deposition on Ca(OH)2-doped PCL, and not on CaCO3-doped PCL. This was attributed to the higher solubility of Ca(OH)2, compared to CaCO3. Minimal CaP deposition was observed on PCL/PEG/PCL triblock copolymers. This was attributed to the low Ca(OH)2 concentration in these samples. For all mineralised samples in the SBF studies, the formation of carbonated HAP was observed. Overall, the synthesis of PCL/PEG/PCL copolymers using the PEG / CaH2 co-initiator was found to be a suitable method for preparing reproducible materials. The calcium-based initiator was also found to have potential for increasing the bioactivity of PCL-based materials.

The environmental menace associated with the existing eco-unfriendly conventional plastics prompted the exploration of natural polymers such as starch for the development of biodegradable plastics. These efforts have seen starch used in various ways, one of which is in the processing of thermoplastic starch (TPS). Thermoplastic starch (also known as plasticized starch) is the product of the interaction between starch and a plasticizer in the presence of thermomechanical energy. While starch blends with conventional plastics only yield products that biofragment, thermoplastic starch (TPS) offers a completely biodegradable option. However, it is limited in application due to its weak mechanical strength and poor moisture resistance. To this end, the objective of this study was to determine the effects of incorporating polycaprolactone (PCL) and flax fiber into glycerol-plasticized pea starch. The effects of processing moisture content on the physical properties of glycerol-plasticized pea starch were also evaluated. The physical properties investigated included morphology, tensile properties, moisture absorption, and thermal properties.<p> Accordingly, two thermoplastic pea starch mixtures containing 9.3 and 20% processing moisture contents were prepared while maintaining starch (pea starch) and glycerol in ratio 7:3 by weight (dry basis). Polycaprolactone was then compounded at 0, 10, 20, 30, and 40% by weight in the solid phase with the TPS mixtures to determine the effects of processing moisture content and PCL incorporation on the physical properties of glycerol-plasticized pea starch. This experiment was structured as a 2 x 5 factorial completely randomized design at 5% level of significance. Subsequently, PCL and flax fiber were compounded with the TPS mixture containing 20% processing moisture to determine the effects of PCL (0, 20, and 40% wt) and flax fiber (0, 5, 10, and 15% wt) incorporation on the physical properties of glycerol-plasticized pea starch. This was structured as a 3 x 4 factorial completely randomized design at 5% level of significance. All the samples were compressed at 140°C for 45 min under 25000-kg load. The compression-molded samples were characterized using scanning electron microscopy (SEM), tensile test, moisture absorption test, and differential scanning calorimetry (DSC) techniques.<p> The tensile fracture surfaces showed a moisture-induced fundamental morphological difference between the two TPSs. The TPS prepared at 20% processing moisture content revealed complete starch gelatinization, thus, exhibiting a rather continuous phase whereas the TPS prepared at 9.3% processing moisture content revealed instances of ungelatinized and partly gelatinized pea starch granules. Consequently, the tensile strength, yield strength, Youngs modulus, and elongation at break increased by 208.6, 602.6, 208.5, and 292.0%, respectively at 20% processing moisture content. The incorporation of PCL reduced the degree of starch gelatinization by interfering with moisture migration during compression molding due to its (PCL) hydrophobicity. At both processing moisture levels of 9.3 and 20%, PCL incorporation had significant impacts on the tensile properties of the plasticized pea starch. Flax fiber incorporation also increased the tensile strength, yield strength, and Youngs modulus while concomitantly reducing the elongation at break of the plasticized pea starch. In the TPS/PCL/flax fiber ternary composites, both PCL and flax fiber improved the tensile strength by acting as independent reinforcing materials as no PCL-fiber interfacial bonding was observed. Maximum tensile strength of 11.55 MPa was reached at 10% flax fiber and 40% PCL reinforcement. While the PCL-TPS interfacial interaction was poor, some degree of TPS-flax fiber interfacial bonding was noticed due to their chemical similarity.<p> TPS prepared at 20% moisture showed more moisture affinity than that prepared at 9.3% moisture. The moisture absorption of TPS dropped progressively with the addition of hydrophobic PCL. Fiber incorporation also reduced moisture absorption by the plasticized pea starch. PCL-fiber incorporation also yielded improved moisture resistance vis-à-vis pure TPS. Finally, the TPS processed at 9.3% moisture exhibited higher thermal stability than that processed at 20%. Individual components of the composites retained their respective thermal properties, thus, implying thermodynamic immiscibility.

The environmental menace associated with the existing eco-unfriendly conventional plastics prompted the exploration of natural polymers such as starch for the development of biodegradable plastics. These efforts have seen starch used in various ways, one of which is in the processing of thermoplastic starch (TPS). Thermoplastic starch (also known as plasticized starch) is the product of the interaction between starch and a plasticizer in the presence of thermomechanical energy. While starch blends with conventional plastics only yield products that biofragment, thermoplastic starch (TPS) offers a completely biodegradable option. However, it is limited in application due to its weak mechanical strength and poor moisture resistance. To this end, the objective of this study was to determine the effects of incorporating polycaprolactone (PCL) and flax fiber into glycerol-plasticized pea starch. The effects of processing moisture content on the physical properties of glycerol-plasticized pea starch were also evaluated. The physical properties investigated included morphology, tensile properties, moisture absorption, and thermal properties.<p> Accordingly, two thermoplastic pea starch mixtures containing 9.3 and 20% processing moisture contents were prepared while maintaining starch (pea starch) and glycerol in ratio 7:3 by weight (dry basis). Polycaprolactone was then compounded at 0, 10, 20, 30, and 40% by weight in the solid phase with the TPS mixtures to determine the effects of processing moisture content and PCL incorporation on the physical properties of glycerol-plasticized pea starch. This experiment was structured as a 2 x 5 factorial completely randomized design at 5% level of significance. Subsequently, PCL and flax fiber were compounded with the TPS mixture containing 20% processing moisture to determine the effects of PCL (0, 20, and 40% wt) and flax fiber (0, 5, 10, and 15% wt) incorporation on the physical properties of glycerol-plasticized pea starch. This was structured as a 3 x 4 factorial completely randomized design at 5% level of significance. All the samples were compressed at 140°C for 45 min under 25000-kg load. The compression-molded samples were characterized using scanning electron microscopy (SEM), tensile test, moisture absorption test, and differential scanning calorimetry (DSC) techniques.<p> The tensile fracture surfaces showed a moisture-induced fundamental morphological difference between the two TPSs. The TPS prepared at 20% processing moisture content revealed complete starch gelatinization, thus, exhibiting a rather continuous phase whereas the TPS prepared at 9.3% processing moisture content revealed instances of ungelatinized and partly gelatinized pea starch granules. Consequently, the tensile strength, yield strength, Youngs modulus, and elongation at break increased by 208.6, 602.6, 208.5, and 292.0%, respectively at 20% processing moisture content. The incorporation of PCL reduced the degree of starch gelatinization by interfering with moisture migration during compression molding due to its (PCL) hydrophobicity. At both processing moisture levels of 9.3 and 20%, PCL incorporation had significant impacts on the tensile properties of the plasticized pea starch. Flax fiber incorporation also increased the tensile strength, yield strength, and Youngs modulus while concomitantly reducing the elongation at break of the plasticized pea starch. In the TPS/PCL/flax fiber ternary composites, both PCL and flax fiber improved the tensile strength by acting as independent reinforcing materials as no PCL-fiber interfacial bonding was observed. Maximum tensile strength of 11.55 MPa was reached at 10% flax fiber and 40% PCL reinforcement. While the PCL-TPS interfacial interaction was poor, some degree of TPS-flax fiber interfacial bonding was noticed due to their chemical similarity.<p> TPS prepared at 20% moisture showed more moisture affinity than that prepared at 9.3% moisture. The moisture absorption of TPS dropped progressively with the addition of hydrophobic PCL. Fiber incorporation also reduced moisture absorption by the plasticized pea starch. PCL-fiber incorporation also yielded improved moisture resistance vis-à-vis pure TPS. Finally, the TPS processed at 9.3% moisture exhibited higher thermal stability than that processed at 20%. Individual components of the composites retained their respective thermal properties, thus, implying thermodynamic immiscibility.

Orthopaedic reconstruction often involves the surgical introduction of structural implants that provide for rigid fixation, skeletal stabilization, and bone integration. The high stresses incurred by these implanted devices have historically limited material choices to metallic and select polymeric formulations. While mechanical requirements are achieved, these non-degradable materials do not participate actively in the remodeling of the skeleton and present the possibility of long-term failure or rejection. This is particularly relevant in cervical fusion, an orthopaedic procedure to treat damaged, degenerative or diseased intervertebral discs. A significant improvement on the available synthetic bone replacement/regeneration options for implants to treat these conditions in the cervical spine may be achieved with the development of primarily mineral biocomposites comprised of a bioactive ceramic matrix reinforced with a biodegradable polymer. Such a biocomposite may be engineered to possess the clinically required mechanical properties of a particular application, while maintaining the ability to be remodeled completely by the body. A biocomposite of Si-doped calcium phosphate (Si-CaP) and poly(ε-caprolactone) (PCL) was developed for application as such a synthetic bone material for potential use as a fusion device in the cervical spine. In this thesis, a method by which high mineral content Si-CaP/PCL biocomposites with interpenetrating matrices of mineral and polymer phases may be prepared will be demonstrated, in addition to the effects of the various preparation parameters on the biocomposite density, porosity and mechanical properties. This new technique by which dense, primarily ceramic Si-CaP/PCL biocomposites were prepared, allowed for the incorporation of mineral contents ranging between 45-97vol%. Polymer infiltration, accomplished solely by passive capillary uptake over several days, was found to be capable of fully infiltrating the microporosity of the sintered calcium phosphate ceramic. After infiltration, these biocomposite materials demonstrated an increase in compressive strength, flexural strength and Young’s modulus with increasing ceramic content and met design targets for use as a cervical fusion prosthesis. The biocomposite was amenable to shaping and drilling and was found to maintain its strength after 30 days immersion in Earle’s Balanced Salt. / Thesis (Ph.D, Mechanical and Materials Engineering) -- Queen's University, 2009-11-24 16:18:16.461

The ultimate goal of this research was to develop a “self-fitting” shape memory polymer (SMP) scaffold for the repair of craniomaxillofacial (CMF) bone defects. CMF defects may be caused by trauma, tumor removal or congenital abnormalities and represent a major class of bone defects. Their repair with autografts is limited by availability, donor site morbidity and complex surgical procedures. In addition, shaping and positioning of these rigid grafts into irregular defects is difficult. Herein, we have developed SMP scaffolds which soften at T > ~56 °C, allowing them to conformally fit into a bone defect. Upon cooling to body temperature, the scaffold becomes rigid and mechanically locks in place. This research was comprised of four major studies. In the first study, photocrosslinkable acrylated (AcO) SMP macromers containing a poly(ε-caprolactone) (PCL) segment and polydimethylsiloxane (PDMS) segments were synthesized with the general formula: AcO-PCL40-block-PDMSm-block-PCL40-OAc. By varying the PDMS segment length (m), solid SMPs with highly tunable mechanical properties and excellent shape memory abilities were prepared. In the second study, porous SMP scaffolds were fabricated based on AcO-PCL40-block-PDMS37-block-PCL40-OAc via a revised solvent casting particulate leaching (SCPL) method. By tailoring scaffold parameters including salt fusion, macromer concentration and salt size, scaffold properties (e.g. pore features, compressive modulus and shape memory behavior) were tuned. In the third study, porous SMP scaffolds were produced from macromers with variable PDMS segment lengths (m = 0 – 130) via an optimized SCPL method. The impact on pore features, thermal, mechanical, and shape memory properties as well as degradation rates were investigated. In the final study, a bioactive polydopamine coating was applied onto pore surfaces of the SMP scaffold prepared from PCL diacrylate. The thin coating did not affect intrinsic bulk properties of the scaffold. However, the coating significantly increased its bioactivity, giving rise to the formation of “bone-bonding” hydroxyapatite (HAp) when exposed to simulated body fluid (SBF). It was also shown that the coating largely enhanced the scaffold’s capacities to support osteoblasts adhesion, proliferation and osteogenesis. Thus, the polydopamine coating should enhance the performance of the “self-fitting” SMP scaffolds for the repair of bone defects.

Please read the abstract in the dissertation Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Physiology / unrestricted

Le procédé d’électro-filage est devenu une technique privilégiée pour la préparation des matériaux nano-fibreux, grâce à sa simplicité de mise en oeuvre, la polyvalence des matières premières utilisées, ainsi que la diversité des structures obtenues. Sa capacité à produire des réseaux fibrillaires, proches de ceux du vivant ont ouvert la voie à d’importantes applications en ingénierie tissulaire. Cette étude a porté sur i) l'élaboration de nano-fibres à base de biopolymères commerciaux par un procédé d’électro-filage, pour des applications en ingénierie tissulaire, ii) leur fonctionnalisation et, iii) l’étude par SANS de la stabilité des chaînes de polymères constituant ces fibres. La stabilité d’un polymère est un facteur important pour la dégradation contrôlée dans les systèmes biologiques. Des études de la stabilité de polystyrène, utilisé ici comme un modèle simple, dans le milieu confiné des nanofibres, ont été élaborés avec la technique de diffusion de neutrons aux petits angles. L’investigation de la conformation des chaînes de polymère dans les nanofibres montre une anisotropie remarquable, en suggérant une forte déformation des chaînes dans la direction axiale des fibres d’au cours de procédé d’électro-filage. La dynamique de relaxation des chaînes a permis d’évaluer leur stabilité et vieillissement dans le milieu confiné des nanofibres. Des fibres biocompatibles à base de poly(-caprolactone) (PCL) ont été électro-filées et optimisées pour obtenir des matériaux nano-structurés et fonctionnalisés en vue d’applications biomédicales. L’introduction par chimie click azide-alcyne de groupes saccharidiques dans le coeur ou en surface des fibres de PCL a été réalisée très efficacement selon deux approches distinctes avant ou après électro-filage. Les caractérisations physico-chimiques et biologiques réalisées sur les différents systèmes ont notamment permis de mettre en évidence la biodisponibilité des sucres à la surface des fibres ainsi que leur capacité à rendre la PCL hydrophile. Ces résultats attestent du potentiel de la chimie click à permettre la fonctionnalisation de fibres de polyesters sans altération de leur structure ouvrant ainsi d’importantes perspectives dans le domaine de l’ingénierie tissulaire. / Electrospinning process has become a leading technique for producing nano-fibrous scaffolds that are highly porous, lighter, and with superior mechanical properties than their bulk equivalents. Structural properties of electrospun fibers closely resemble to the connective cell tissue, making these nonwovens readily employed in medicine and pharmacy. The research study of this thesis focused on bridging the commercially available biopolymers with the tissue engineering applications through multifunctional aspects of carbohydrates and click chemistry coupling. Biocompatible fibers were electrospun from poly(-caprolactone) and further optimized into clickable azido-PCL scaffolds. Their surface-activity was visualized after click coupling of a fluorescent dye onto PCL-based electrospun fibers, while hydrophilicity and bioactivity were achieved by covalent bonding of carbohydrates, enabling specific cell adhesion possibilities of these nonwovens. Selective lectin surface-immobilization revealed the potential of these scaffolds for specific protein adhesion and therefore controlled cell-material interactions. Polymer stability is an important factor for controlled degradation in tissue engineering applications. Small angle neutron scattering studies were carried out to estimate the stability of polystyrene as a model-polymer, its chain conformation in as-spun and thermally annealed electrospun fibers. Notable anisotropy of polymeric chains within the fibers was observed. The terminal relaxation time of the polystyrene was estimated and compared to the theoretical value.

<p>In this work, an in-depth analysis of crystalline characteristics has been performed for a unique set of strictly monodisperse poly-ε-caprolactone (PCL) oligomers. The molecules have different sets of end groups with various degrees of bulkiness and hydrogen bonding potential, affecting their aptitude to pack in ordered crystal structures. The oligomers also have different numbers of repeating units (<em>n </em>= 2-64), affecting the degree to which end groups influence overall molecular characteristics. The presence of bulky end groups leads to an innate confinement effect on crystallisation which in turn makes it possible to utilize the set of PCL oligomers to study confined space crystallisation. Confined space crystallisation is explored as a route to gain further understanding about the early metastable phases in crystal formation.</p><p> </p><p>The monodisperse nature of the samples made it possible to collect very precise small-angle and wide-angle X-ray scattering data (SAXS and WAXS) as well as calorimetric data. Computer modeling studies were performed to support experimental findings. It was shown that end groups strongly affected crystallisation features for the shorter oligomers (<em>n </em>≤ 8) but to a lesser extend for the longer oligomers (<em>n </em>≥ 16). The presence of a bulky end group at one end of an oligomer could inhibit the formation of hydrogen bonds on the other end. Short oligomers (<em>n</em> = 8) with OH-end groups exhibited novel packing characteristics. At one isothermal crystallisation temperature the molecules exhibited not only lamellar ordering but also an additional, likely rectangular or slanted, ordering. The sample was packed in a unique structure with molecular chains lying parallel but not aligned head to head with each other. At a higher crystallisation temperature the molecules packed in a double layered structure and at an even higher temperature in a typical non-folded but tilted single-molecular layer pattern.</p><p> </p><p>Unit cell determination was performed for a short oligomer with two bulky end groups, showing the existence of a tetragonal unit cell with different dimensions than the orthorhombic unit cells previously reported for linear PCL without end groups. To gain greater insight into the earliest stages of molecular packing, in situ WAXS measurements were performed using a synchrotron radiation beam and measuring data each 12 s whilst very slowly going from melt to isothermal crystallisation. It was shown that the crystal unit cell was distorted during the first minutes of slow crystallisation, which might either represent a metastable phase or else a highly distorted orthorhombic phase.</p>

Abdominal aortic aneurysm (AAA) is a prevalent disease in developed countries. While endovascular aneurysm repair is fairly successful, it has shortcomings. Polymeric endoluminal paving and sealing is a method that has previously been developed to treat a range of diseases. Our goal is to further develop this technique to treat AAA, a process we have named polymeric endo-aortic paving (PEAP). We hypothesize that PEAP will overcome many of the limitations associated with EVAR by providing a minimally invasive treatment which can be used on patients with complicated AAA geometries and reducing incidence of migration and endoleak. Additionally, we plan to incorporate drug delivery into PEAP to improve efficacy. The purpose of this work was to evaluate a potential graft material for PEAP and to develop a thrombus mimic which will aid in further PEAP development. Blends of polycaprolactone/polyurethane (PCL/PU) were assessed by characterizing their mechanical, thermoforming, and degradation properties. PCL/PU grafts have a similar stiffness to aortic tissue and can be thermoformed at temperatures approaching 37 degrees C. Blending PCL with PU significantly reduces PCL's degradation. An anisotropic hyperelastic strain energy function was developed for the PCL/PU blends and finite element modeling (FEM) was used to show that stress reduction on the AAA wall that can be achieved by PEAP is similar to current EVAR. Stiffness varies throughout the AAA thrombus, and thrombus mimics were developed that have similar stiffness, components, and structure to native AAA thrombus.

Electrospinning is a polymer processing technique which allows for the production of nano to micro size fibers and scaffolds which can be composed of numerous synthetic biodegradable materials and natural biopolymers. Natively, elastin and collagen are the main components of vascular tissue. Arranged in a tri-layered structure, they create a specific mechanical environment that can withstand the rigors of circulation. The goal of this study was to develop a mechanically ‘biomimicking’ vascular graft composed of three distinct layers through the process of electrospinning. We hypothesize that the use of bioactive agents such as elastin, collagen, and silk to supplement poly(caprolactone) at specified ratios for each layer would provide a finely tuned vascular replacement. This was accomplished by establishing cross-linking parameters for the biopolymer materials and then assessing the mechanical properties of individual materials and eventually a whole tri-layered graft. Additionally, while mechanical testing can lead to a good graft, a replacement graft requires excellent cellular properties as well to promote cell infiltration, proliferation, and migration. Therefore, the conclusion of this study examines the integrin binding characteristics of the electrospun biopolymers. First, the results from the preliminary cross-linking study examined the dissipation of soluble elastin when uncross-linked v. cross-linked. It was determined through this initial study that synthetic scaffolds blended with soluble proteins such as elastin require a fixation in order to retain their protein mass within the scaffold. Retaining this mass, incrementally changed the material properties of the blended scaffolds. This initial study was then carried further to establish optimal cross-linking parameters using two different types of reagents: carbodiimide and genipin. It was found that lower cross-linking molarities produced excellent results based on assays performed to assess cross-linking percentages and rate of reaction. Some differences in mechanical properties were seen, but they did not constitute a choice of one cross-linker over the other. The next portion of this study aimed to design a tri-layered graft. This was performed with the aid of mathematical analysis to observe circumferential wall stresses based on simple tensile properties. A series of tri-layered grafts were electrospun using poly(caprolactone), elastin, and collagen. The medial layers of these grafts were changed while the intima and adventitia remained constant. Differences were demonstrated as the elastin content of the medial layer decreased, proving that each layer had an affect on the overall graft properties and that it was possible to tune graft mechanics. A larger tri-layered study looked to evaluate changes in the adventitial and medial layers while keeping the intimal layer constant using poly(caprolactone), elastin, collagen, and silk fibroin. In this study, differences were exhibited under compliance and burst strength testing, narrowing the scope of material choices. Results from a 4 week degradation study with the best tri-layered grafts revealed no evidence of degradation, but did generate some positive compliance results for two of the grafts. Finally, integrin binding and protein analysis portrayed results that were indicative of the existence of ligand binding sites for collagen scaffolds and the possibility of a small amount of ligand sites on silk. Elastin, however, displayed low to non-existent adhesion. These studies produced results that allowed us to continuously narrow the scope of materials as the experiment progressed towards an optimized tri-layered vascular graft.