Bioactive Glass in Lumbar Spondylodesis. A Pre-Clinical and Clinical Study

Bioactive glasses (BGs) form a group of synthetic, surface-active, composition-dependent, silica-based biomaterials with osteoconductive, osteopromotive, and even angiogenic, as well as antibacterial, properties. A national interdisciplinary research group, within the Combio Technology Program (2003–2007), developed a porous load-bearing composite for surgical applications made of BG 1–98 and polymer fibers. The pre-clinical part of this thesis focused on the in vitro and in vivo testing of the composite materials in a rabbit femur and spinal posterolateral fusion model. The femur model failed to demonstrate the previously seen positive effect of BG 1–98 on osteogenesis, probably due to the changed resorption properties of BG in the form of fibers. The spine study was terminated early due to adverse events. In vitro cultures showed the growth inhibition of human mesenchymal stems next to BG 1–98 fibers and radical pH changes. A prospective, long-term, follow-up study was conducted on BG–S53P4 and autogenous bone used as bone graft substitutes for instrumented posterolateral spondylodesis in the treatment of degenerative spondylolisthesis (n=17) and unstable burst fractures (n=10) during 1996–1998. The operative outcome was evaluated from X-rays and CT scans, and a clinical examination was also performed. On the BG side, a solid fusion was observed in the CT scans of 12 patients, and a partial fusion was found in 5 patients, the result being a total fusion rate in all fusion sites (n=41) 88% for levels L4/5 and L5/S1 in the spondylolisthesis group. In the spine fracture group, solid fusion was observed in five patients, and partial fusion was found in five resulting in a total fusion rate of 71% of all fusion sites (n=21). The pre-clinical results suggest that under certain conditions the physical form of BG can be more critical than its chemical composition when a clinical application is designed. The first long-term clinical results concerning the use of BG S53P4 as bone graft material in instrumented posterolateral spondylodesis seems to be a safe procedure, associated with a very low complication rate. BG S53P4 used as a stand-alone bone substitute cannot be regarded as being as efficient as AB in promoting solid fusion.

Designing sustainable industrial ecosystems : the case of a biogas-for-traffic solution

This thesis focuses on the development of sustainable industrial architectures for bioenergy based on the metaphors of industrial symbiosis and industrial ecosystems, which imply exchange of material and energy side-flows of various industries in order to improve sustainability of those industries on a system level. The studies on industrial symbiosis have been criticised for staying at the level of incremental changes by striving for cycling waste and by-flows of the industries ‘as is’ and leaving the underlying industry structures intact. Moreover, there has been articulated the need for interdisciplinary research on industrial ecosystems as well as the need to extend the management and business perspectives on industrial ecology. This thesis addresses this call by applying a business ecosystem and business model perspective on industrial symbiosis in order to produce knowledge on how industrial ecosystems can be developed that are sustainable environmentally and economically. A case of biogas business is explored and described in four research papers and an extended summary that form this thesis. Since the aim of the research was to produce a normative model for developing sustainable industrial ecosystems, the methodology applied in this research can be characterised as constructive and collaborative. A constructive research mode was required in order to expand the historical knowledge on industrial symbiosis development and business ecosystem development into the knowledge of what should be done, which is crucial for sustainability and the social change it requires. A collaborative research mode was employed through participating in a series of projects devoted to the development of a biogas-for-traffic industrial ecosystem. The results of the study showed that the development of material flow interconnections within industrial symbiosis is inseparable from larger business ecosystem restructuring. This included a shift in the logic of the biogas and traffic fuel industry and a subsequent development of a business ecosystem that would entail the principles of industrial symbiosis and localised energy production and consumption. Since a company perspective has been taken in this thesis, the role of an ecosystem integrator appeared as a crucial means to achieve the required industry restructuring. This, in turn, required the development of a modular and boundary-spanning business model that had a strong focus on establishing collaboration among ecosystem stakeholders and development of multiple local industrial ecosystems as part of business growth. As a result, the designed business model of the ecosystem integrator acquired the necessary flexibility in order to adjust to local conditions, which is crucial for establishing industrial symbiosis. This thesis presents a normative model for the development of a business model required for creating sustainable industrial ecosystems, which contributes to approaches at the policy-makers’ level, proposed earlier. Therefore, this study addresses the call for more research on the business level of industrial ecosystem formation and the implications for the business models of the involved actors. Moreover, the thesis increases the understanding of system innovation and innovation in business ecosystems by explicating how business model innovation can be the trigger for achieving more sustainable industry structures, such as those relying on industrial symbiosis.

Computational models for and from biology : simple gene assembly and reaction systems

The advancement of science and technology makes it clear that no single perspective is any longer sufficient to describe the true nature of any phenomenon. That is why the interdisciplinary research is gaining more attention overtime. An excellent example of this type of research is natural computing which stands on the borderline between biology and computer science. The contribution of research done in natural computing is twofold: on one hand, it sheds light into how nature works and how it processes information and, on the other hand, it provides some guidelines on how to design bio-inspired technologies. The first direction in this thesis focuses on a nature-inspired process called gene assembly in ciliates. The second one studies reaction systems, as a modeling framework with its rationale built upon the biochemical interactions happening within a cell. The process of gene assembly in ciliates has attracted a lot of attention as a research topic in the past 15 years. Two main modelling frameworks have been initially proposed in the end of 1990s to capture ciliates’ gene assembly process, namely the intermolecular model and the intramolecular model. They were followed by other model proposals such as templatebased assembly and DNA rearrangement pathways recombination models. In this thesis we are interested in a variation of the intramolecular model called simple gene assembly model, which focuses on the simplest possible folds in the assembly process. We propose a new framework called directed overlap-inclusion (DOI) graphs to overcome the limitations that previously introduced models faced in capturing all the combinatorial details of the simple gene assembly process. We investigate a number of combinatorial properties of these graphs, including a necessary property in terms of forbidden induced subgraphs. We also introduce DOI graph-based rewriting rules that capture all the operations of the simple gene assembly model and prove that they are equivalent to the string-based formalization of the model. Reaction systems (RS) is another nature-inspired modeling framework that is studied in this thesis. Reaction systems’ rationale is based upon two main regulation mechanisms, facilitation and inhibition, which control the interactions between biochemical reactions. Reaction systems is a complementary modeling framework to traditional quantitative frameworks, focusing on explicit cause-effect relationships between reactions. The explicit formulation of facilitation and inhibition mechanisms behind reactions, as well as the focus on interactions between reactions (rather than dynamics of concentrations) makes their applicability potentially wide and useful beyond biological case studies. In this thesis, we construct a reaction system model corresponding to the heat shock response mechanism based on a novel concept of dominance graph that captures the competition on resources in the ODE model. We also introduce for RS various concepts inspired by biology, e.g., mass conservation, steady state, periodicity, etc., to do model checking of the reaction systems based models. We prove that the complexity of the decision problems related to these properties varies from P to NP- and coNP-complete to PSPACE-complete. We further focus on the mass conservation relation in an RS and introduce the conservation dependency graph to capture the relation between the species and also propose an algorithm to list the conserved sets of a given reaction system.

Show me your brain! Stories of interdisciplinary knowledge creation in practice. Experiences and observations from Aalto Design Factory, Finland.

This dissertation centres on the themes of knowledge creation, interdisciplinarity and knowledge work. My research approaches interdisciplinary knowledge creation (IKC) as practical situated activity. I argue that by approaching IKC from the practice-based perspective makes it possible to “deconstruct” how knowledge creation actually happens, and demystify its strong intellectual, mentalistic and expertise-based connotations. I have rendered the work of the observed knowledge workers into something ordinary, accessible and routinized. Consequently this has made it possible to grasp the pragmatic challenges as well the concrete drivers of such activity. Thus the effective way of organizing such activities becomes a question of organizing and leading effective everyday practices. To achieve that end, I have conducted ethnographic research of one explicitly interdisciplinary space within higher education, Aalto Design Factory in Helsinki, Finland, where I observed how students from different disciplines collaborated in new product development projects. I argue that IKC is a multi-dimensional construct that intertwines a particular way of doing; a way of experiencing; a way of embodied being; and a way of reflecting on the very doing itself. This places emphasis not only the practices themselves, but also on the way the individual experiences the practices, as this directly affects how the individual practices. My findings suggest that in order to effectively organize and execute knowledge creation activities organizations need to better accept and manage the emergent diversity and complexity inherent in such activities. In order to accomplish this, I highlight the importance of understanding and using a variety of (material) objects, the centrality of mundane everyday practices, the acceptance of contradictions and negotiations well as the role of management that is involved and engaged. To succeed in interdisciplinary knowledge creation is to lead not only by example, but also by being very much present in the very everyday practices that make it happen.