Magnesium (Mg) and its alloys offer potential as a new class of degradable metallic orthopaedic biomaterials. In comparison with current metallic orthopaedic implant materials, Mg offers advantages such as, high specific strength, closer-to-bone stiffness and biodegradability, thereby eliminating the need for a second surgery to remove hardware. The use of porous metal foams as biomaterial scaffolds has been widely adopted, however, many of these porous structures are manufactured with pore architectures that are inherently random. This makes structural optimisation for a specific purpose challenging. Scaffolds containing ordered pore architectures can be fabricated to meet design criteria, such as porosity, stiffness, and volume fraction. Currently there are few methods described in the literature to manufacture ordered porous Mg. The main aim of this thesis was to determine the resolution of a novel indirect solid free-form fabrication (SFF) process for producing topologically-ordered porous Mg (TOPM) structures from pure Mg and commercial Mg alloys. The produced structures were examined for properties such as dimensional accuracy, microstructure, surface properties, mechanical properties and corrosion behaviour. The capability of the process was further examined in manufacturing structures with complex architecture for potential application as degradable metallic orthopaedic devices, namely a spinal fusion device (SFD) and screw. With the produced structures aimed at load-bearing applications in bone, the mechanical properties and behaviour of the TOPM and SFD made from Mg alloys were investigated using finite element analysis (FEA) and compression testing. The relationship between surface roughness and degradation behaviour in Mg biomaterials has received limited interest and is still a controversial issue. Therefore, it was necessary to accurately determine the effect of surface roughness on corrosion rate of Mg, especially samples manufactured from SFF and casting of molten Mg. Given the well-established need for improved corrosion resistance of Mg, two coating techniques, including biomimetic calcium phosphates and electrochemically-assisted deposition coating, were applied on Mg substrates cast via the SFF process. Corrosion testing was employed to investigate the effectiveness of the coating layers in improving corrosion resistance. In this thesis, the capability of the SFF manufacturing process and properties of the produced structures were thoroughly investigated. Results and findings contribute to the development of topology optimised, degradable Mg devices for biomedical applications.

No description available.

<p>Validerat; 20130918 (global_studentproject_submitter)</p>

Diabetes is a chronic metabolic disorder whereby the body loses its ability to maintain normal glucose levels. Despite of development of implantable glucose sensors in long periods, none of the biosensors are capable of continuously monitoring glucose levels during long-term implantation reliably. Progressive loss of sensor function occurs due in part to biofouling and to the consequences of a foreign body response such as inflammation, fibrosis, and loss of vasculature. In order to improve the function and lifetime of implantable glucose sensors, a new 3D porous and bio-stable collagen scaffold has been developed to improve the biocompatibility of implantable glucose sensors. The novel collagen scaffold was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability. NDGA-treated collagen scaffolds were stable without any physical deformation in the subcutaneous tissue of rats for 4 weeks. The scaffold application does not impair the function of our sensor. The effect of the scaffolds on sensor function and biocompatibility was examined during long-term in vitro and in vivo experiments and compared with control bare sensors. The sensitivity of the short sensors was greater than the sensitivity of long sensors presumably due to less micro-motions in the sub-cutis of the rats. The NDGA-crosslinked scaffolds induced much less inflammation and retained their physical structure in contrast to the glutaraldehyde (GA)-crosslinked scaffolds. We also have developed a new dexamethasone (Dex, anti-inflammatory drug)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres/porous collagen scaffold composite for implantable glucose sensors. The composite system showed a much slower and sustained drug release than the standard microspheres. The composite system was also shown to not significantly affect the function of the sensors. The sensitivity of the sensors with the composite system in vivo remained higher than for sensors without the composites (no scaffold, scaffold without microspheres). Histology showed that the inflammatory response to the Dex-loaded composite was much lower than for the control scaffold. The Dex-loaded composite system might be useful to reduce inflammation to glucose sensors and therefore extend their function and lifetime.

60 % of school children have some form of untreated tooth decay or have suffered trauma to the front teeth which results in pulp damage. If left untreated, these teeth are susceptible to premature fracture/loss under daily stresses. In cases of adolescent tooth loss, teenagers cannot get dental implants until after the growth spurts; their only option is using removable dentures which lowers their quality of life. Conventional endodontic treatment (root canal treatment) is used in cases of pulp necrosis, but cannot be performed in immature permanent teeth due to major differences in tooth anatomy. Currently the American Dental Academy has approved a procedure called Regenerative Endodontic Treatment (RET) for such cases, but the outcomes are still unpredictable and the method is largely unreliable. One issue that we are trying to address in this work is the regeneration of the pulp-dentin complex (PDC), specifically the interface. Endeavors in regenerating either pulp or dentin have been successful individually, but the interface region is the anatomical and physiologic hallmark of the PDC and has not been addressed. We have proposed a biomimetic scaffold to facilitate early stage stratification of these different tissues and allow recapitulation of their interface. Tissue engineering principles and biomaterial processing techniques were used simultaneously to encourage dental pulp stem cells into mineralize selectively only on one side. This effectively allows the scaffold to serve as the interface region between the hard dentin and the soft vascular pulp. / Bioengineering

<p>The use of synthetic materials for tissue and organ reconstruction, i. e. tissue engineering, has become a promising alternative to current surgical therapies and may overcome the shortcomings of the methods in use today. The challenge is in the design and reproducible fabrication of biocompatible and bioresorbable polymers, with suitable surface chemistry, desirable mechanical properties, and the wanted degradation profile. These material properties can be achieved in various manners, including the synthesis of homo- and copolymers along with linear and star-shaped architectures. In many applications the materials’ three-dimensional structure is almost as important as its composition and porous scaffolds with high porosity and interconnected pores that facilitate the in-growth of cells and transportation of nutrients and metabolic waste is desired.</p><p>In this work linear and star-shaped polymers have been synthesized by ring-opening polymerization using a stannous-based catalyst and a spirocyclic tin initiator. A series of linear copolymers with various combinations of 1,5-dioxepane-2-one (DXO), Llactide (LLA) and ε-caprolactone (CL) have been polymerized using stannous octoate as catalyst. It is shown that the composition of the polymers can be chosen in such a manner that the materials’ mechanical and thermal properties can be predetermined. A solvent-casting and particulate leaching scaffold preparation technique has been developed and used to create three-dimensional structures with interconnected pores. The achieved physical properties of these materials’ should facilitate their use in both soft and hard tissue regeneration.</p><p>Well defined star-shaped polyesters have been synthesized using a spirocyclic tin initiator where L-lactide was chosen as a model system for the investigation of the polymerization kinetics. Neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star-shaped polymers, which all show a molecular weight distribution below 1.19 and a molecular weight determined by the initial monomer-to-initiator concentration.</p>

The use of synthetic materials for tissue and organ reconstruction, i. e. tissue engineering, has become a promising alternative to current surgical therapies and may overcome the shortcomings of the methods in use today. The challenge is in the design and reproducible fabrication of biocompatible and bioresorbable polymers, with suitable surface chemistry, desirable mechanical properties, and the wanted degradation profile. These material properties can be achieved in various manners, including the synthesis of homo- and copolymers along with linear and star-shaped architectures. In many applications the materials’ three-dimensional structure is almost as important as its composition and porous scaffolds with high porosity and interconnected pores that facilitate the in-growth of cells and transportation of nutrients and metabolic waste is desired. In this work linear and star-shaped polymers have been synthesized by ring-opening polymerization using a stannous-based catalyst and a spirocyclic tin initiator. A series of linear copolymers with various combinations of 1,5-dioxepane-2-one (DXO), Llactide (LLA) and ε-caprolactone (CL) have been polymerized using stannous octoate as catalyst. It is shown that the composition of the polymers can be chosen in such a manner that the materials’ mechanical and thermal properties can be predetermined. A solvent-casting and particulate leaching scaffold preparation technique has been developed and used to create three-dimensional structures with interconnected pores. The achieved physical properties of these materials’ should facilitate their use in both soft and hard tissue regeneration. Well defined star-shaped polyesters have been synthesized using a spirocyclic tin initiator where L-lactide was chosen as a model system for the investigation of the polymerization kinetics. Neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star-shaped polymers, which all show a molecular weight distribution below 1.19 and a molecular weight determined by the initial monomer-to-initiator concentration. / QC 20101217