There are not enough donor lungs available to meet the increasing demand for lung transplantation. To compound the problem, transplant recipients have a projected survival time of only 5.7 years despite life-long immunosuppression. An alternative approach for acquiring transplantable lungs and reducing post-operative complications may be possible through tissue engineering. Perfusion-decellularization generates natural, three-dimensional extracellular matrix (ECM) scaffolds of an organ that are apt for tissue engineering. Decellularization of the heart, lung, liver, kidney, and pancreas has been reported in animal models and from human tissue. Decellularization of fibrotic and emphysematic lungs indicated that this technique can efficiently remove cells from diseased tissue—a potential source of materials for engineering of transplantable lung tissue. Pulmonary hypertension (PHT) is a vascular disease characterized by increased pulmonary vascular resistance leading to right heart failure and death. Lungs damaged by PHT are unsuitable for transplantation; however, decellularization of these organs may provide scaffolds appropriate for ex vivo lung engineering. Monocrotaline-induced PHT (MCT-PHT) is a well-established model of this disease in rats closely resembling the clinical presentation of PHT in humans. Thus, decellularization and recellularization of hypertensive lungs was evaluated using the MCT-PHT model. Decellularization of control and MCT-PHT Sprague-Dawley rat lungs was accomplished by treating the lungs with Triton X-100, sodium deoxycholate (SDC), NaCl, and DNase. The resulting acellular matrices were extensively characterized by molecular, mechanical, and structural analyses revealing that decellularization was able to remove cells while leaving the ECM components and lung ultrastructure intact; however, the vasculature of MCT-PHT acellular lung scaffolds was narrower than control scaffolds—a hallmark of PHT. To evaluate the effect of narrowed vasculature on the use of hypertensive lungs for tissue engineering, an optimal vascular recellularization technique was developed. Gravity-based seeding of endothelial cells followed by bioreactor-based whole-organ culture resulted in efficient vascular recellularization of control lung scaffolds. However, this method led to heterogeneous re-endothelialization of the vasculature of MCT-PHT matrices suggesting that additional manipulation or optimization is required. / acase@tulane.edu

Soft tissue reconstruction in the nervous system is sensitive to the mechanical and chemical cues of the growth microenvironment. Many technologies have been designed to study these stimuli and their effect on the regional extracellular environment (ECM). Because of the hard-to-achieve and costliness of these technologies, biologists are usually reluctant to employ them to study cellular behaviors. In addition, the complexity of the nervous system, particularly in cases of nerve repair and reconstruction, necessitates the development of facile high- throughput investigational tools. The objective for this dissertation is to examine and manipulate neuronal cell-cell and cell-ECM responses to varying nervous system microenvironment stimuli in a 3-D in vitro model. / acase@tulane.edu

No description available.

Controlled drug delivery systems have been utilized to enhance the therapeutic effects of many current drugs by effectively delivering drugs in a time-dependent and repeatable manner. The ability to control the delivery of drugs, whether through sequential, instantaneous, sustained, delayed and/or enhanced release has the potential to provide effective dosing regimens with enhanced therapeutic effects for a plethora of diseases and injuries. For instance, such systems can enhance anti-tumoral responses or, alternatively, promoting tissue regeneration. The current need for organ and tissue replacement, repair and regeneration for patients is continually growing such that supply is not meeting the high demand primarily due to a paucity of donors as well as biocompatibility issues that lead to immune rejection of the transplant. To overcome this problem, scientists working in the field of tissue engineering and regenerative medicine have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the goal of yielding functional tissues or organs. Continued advancement and hybrid approaches using different material combinations and printing methodologies will further advance the progress of 3D printing technologies toward developing scaffolds, and other implantable drug delivery devices, capable of being utilized in the clinic. Such advancements will not only make inroads into improving structural integrity of implantable devices but will also provide platforms for controlled drug delivery from such devices. The primary focus of this thesis will be on controlled drug delivery as well as the integration of controlled drug delivery into 3D printed devices aimed at promoting tissue regeneration. We initially assessed the efficacy of a controlled drug delivery system for the treatment of cancer using on-demand, and sustained, release of an anticancer drug, doxorubicin (DOX), for the treatment of melanoma in a murine model. Using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with DOX. An in vitro release assay demonstrated an ability of US to affect the release kinetics of DOX from DOX-loaded PLGA microspheres by inducing a 12% increase in rate of release where this treatment resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma-bearing mice treated intratumorally with DOX (8 µg)-loaded microspheres and subjected to US treatment at the tumor site were shown to significantly extended survival compared to untreated mice or mice subjected to either treatment alone. The synergistic increase in survival of melanoma-challenged mice treated with the combination of US and DOX-loaded microspheres implicates a promising additional tool for combatting an otherwise currently incurable cancer. We then further investigated other novel control drug delivery systems which included a 3D printed device (tube) for the purposes of sequential drug delivery. 3D printed hollow alginate tubes were fabricated through co-axial bioprinting and then injected with PLGA to provide sequential release of distinct fluorescent dyes (model drugs), where fluorescein was initially released from alginate followed by the delayed release (up to 55 h) of rhodamine B in PLGA. With an alginate shell and a PLGA core, the fabricated tubes showed no cytotoxicity when incubated with the human embryonic kidney (HEK293) cell line or bone marrow stromal stem cells (BMSC). Microscale printing through two-photon polymerization (2PP) was then investigated for controlled drug delivery potential. Poly(ethylene glycol) dimethacrylate (PEGDMA) devices were fabricated using a Photonic Professional GT two-photon polymerization system while rhodamine B was homogenously entrapped inside the polymer matrix during photopolymerization. These devices were printed with varying porosity and morphology and using varying printing parameters such as slicing and hatching distance. Overall, tuning the hatching distance, slicing distance, and pore size of the fabricated devices provided control of rhodamine B release due to resulting changes in the motility of the small molecule and its access to structure edges. In general, increased spacing provided higher drug release while smaller spacing resulted in some occlusion, preventing media infiltration and thus resulting in reduced drug release. 2PP was further explored for its ability to tailor topographical cues in addition to controlled drug release. These physical cues, similar to those of the ECM, have been seen to promote differentiation. With 2PP, we explored microscale topographies with nanoscale precision, where different star size topographies were fabricated. It was observed that the smallest star size topographies differentiated human iPSCs towards the endoderm and mesoderm germ layer. Integrating the facility for controlled drug release into 3D printed devices provides a demand for constructs that not only need to fulfill their purpose of temporarily substituting for the missing tissue at the site of injury, but also providing the necessary cues to promote appropriate tissue regeneration. With 3D printing technology, novel drug delivery constructs were fabricated and tested to appraise functionality such as the ability to control drug delivery and the ability to function as a non-toxic medium for cellular attachment, proliferation, and forced differentiation.

Trotz hochmoderner Technologien und ausgefeilter therapeutischer und rekonstruktiver chirurgischer Heilungsmethoden beträgt die 5-Jahres Überlebensrate bei der Diagnose PECA der Mundhöhle im Durchschnitt auch im Jahre 2017 nur 55 % und die Heilungsmethoden haben sich in den letzten drei Jahrzehnten kaum verbessert. Umso wichtiger ist es deshalb, die Forschung voranzutreiben und ein aussagekräftiges Tumormodell zu etablieren, das bei der Entwicklung neuer Therapieansätze schnell und sicher gute Ergebnisse liefert. In dieser Studie soll mit Hilfe des Tissue Engineering (TE) ein in gesunder Mundschleimhaut (MSH) integriertes 3D-Tumormodell generiert werden, welches bestmöglich die Analyse pathologischer Mechanismen im Tumorzentrum, sowie im Randbereich von gesundem und erkranktem Gewebe, und auch die Analyse der Auswirkungen neuartiger Chemotherapeutika auf gesunde und maligne Zellen in direkter Nachbarschaft ermöglicht – ohne Tierversuche. In der Konsequenz könnte ein erheblicher Fortschritt mit höheren Erfolgsaussichten der Therapieansätze erzielt werden. Es wird ein Tumormodell generiert, in dem auf Basis eines gesunden MSH-Modells Tumorzellen eingebracht werden, um - genauso, wie die Tumorentstehung in vivo von statten gehen würde – Tumorentstehung und Tumorwachstum in der Umgebung von gesunder MSH analysieren zu können. Das Modell basiert dabei auf einer Matrix aus dezellularisierter, porciner, small-intestinal-submucosa (SIS/MUC), die mit primären Fibroblasten, primären Keratinozyten und Tumorzellen der Tumorzelllinie FaDu besiedelt wird. Eine Besonderheit der FaDu-Zellen ist die vorangegangene Transduktion mit dem Lentivirus RFP – um die eingewanderten Zellen von gesunden Zellen unterscheiden zu können. Der Vorgang der Transduktion war gelungen und es konnte eine Fluoreszenz der noch in Zellkulturschalen kultivierten Zellen erzielt werden. Allerdings waren die fluoreszierenden Zellen in den fixierten Schnitten nicht mehr nachweisbar. Zur Generierung eines Tumormodelles wurden auf Basis eines OMÄ drei unterschiedliche Applikationsformen zur Integration von Tumorzellen getestet. Die Integration von Tumorzellen fand in Form von Spots, Sphäroiden oder Tumorzellgemischen (prim. Keratinozyten/FaDu-Zellen) in zuvor kultivierte gesunde OMÄ statt. Dabei sollte das Applizieren von Spots oder Sphäroiden das Tumorzellwachstum auch in der Umgebung von gesundem Gewebe initiieren. Dies würde die Möglichkeit schaffen, auch in vitro, gesundes neben pathologischem Gewebe und den Übergang dazu genau analysieren zu können. Es sollen sowohl die optimale Konzentration der Tumorzellen, welche für die Entstehung von Tumoren nötig ist, als auch die geeignetste Applikationsmethode eruiert werden, um optimale Tumormodelle zuverlässig reproduzierbar ansetzen zu können. Die Modelle wurden histologisch und immunhistochemisch analysiert und die Ergebnisse mit ermittelten TEER-Werte in Korrelation gesetzt. In dieser Arbeit konnte mit der Applikation von Spots oder Sphäroiden kein suffizientes Tumorwachstum in Umgebung von gesunder MSH erzielt werden. Die Zellen lagen ohne Reaktion des angrenzenden Stratum corneums auf der zu stark ausgeprägten Hornschicht der OMÄ auf und es war keine Einwanderung in das darunterliegende Gewebe möglich. Allerdings ist es gelungen, durch Applikation eines Zellgemisches variierender Mischungsverhältnisse von primären Keratinozyten und Tumorzellen der Zelllinie FaDu ein 3D-Tumorwachstum unterschiedlicher Malignitätsstufen zu initiieren. Je kleiner das Mischungsverhältnis und je höher in der Konsequenz die Anzahl der FaDu-Tumorzellen, desto ausgeprägter waren die morphologischen Anzeichen einer Tumorbildung. Abhängig vom Mischungsverhältnis war dabei die Ausprägung des Tumors. Auch wenn dadurch keine Kombination von gesundem und pathologischem Gewebe in einem Modell mehr imitiert werden konnte, so konnten zumindest nach histologischen und immunhistochemischen Untersuchungen eindeutige pathologische, maligne Tumormodelle generiert werden. Die Tumormodelle zeigten durchgehend Zell- und Kernpleomorphismen, atypische und vermehrte suprabasale Mitosen, eine Störung der normalen Gewebearchitektur, die Ausbildung von Interzellularbrücken, Einzelzelldyskeratosen und Verhornungsknospen, sowie Stellen der Durchbrechung der Basalmembran und Invasion von Tumorzellen in die darunterliegende Lamina propria. All das sind eindeutige Kennzeichen malignen Wachstums Auch die Ergebnisse der TEER-Wert Messung stimmten mit den morphologischen Entwicklungen der Modelle überein. So stiegen die TEER-Werte der Kontrollmodelle konsequent an, was für eine deutliche Entwicklung von kontinuierlichem Gewebe spricht und im Gegensatz dazu fielen die TEER-Werte im zeitlichen Verlauf der Tumormodelle, bei denen die Basalmembran und somit die Kontinuität des Gewebes durchbrochen wurde rapide ab, bzw. lagen im konstant niedrigen Bereich. Der Erfolg der Etablierung dieses zuverlässig rekonstruierbaren 3D, in vitro generierten Tumormodells, das der in vivo Situation eines Plattenepithelkarzinoms sehr nahekommt, bietet der Wissenschaft eine sehr gute Möglichkeit, weitere Studien zum Tumorwachstum durchzuführen. Außerdem kann die Weiterentwicklung und Verbesserung vielversprechender, neuartiger chemotherapeutischer und radiologischer Therapieverfahren erheblich voran¬getrieben und dadurch die Heilungschancen mit geringeren Nebenwirkungen für den Patienten verbessert und eine erhöhte Lebensqualität erzielt werden. / Despite state-of-the-art technologies and sophisticated therapeutic and reconstructive surgical methods, the average 5-year survival rate of patients diagnosed with oral squamous cell carcinoma (OSCC) is still only 55% in 2017. Healing methods have barely improved over the last three decades. Therefore, it is important to establish a meaningful tumour model that delivers fast and reliable results in the development of new therapeutic approaches. In this study, Tissue Engineering is used to generate a three-dimensional tumour model integrated into healthy oral mucosa. This enables an ideal analysis of pathological mechanisms in the tumour center, as well as in the margins of healthy and diseased tissue. It also allows the analysis of the effects of novel chemotherapeutic agents on healthy and malignant cells in proximity - without animal testing. Consequently, a considerable progress could be achieved with a higher chance of success of therapeutic approaches. A tumour model, based on a healthy oral mucosa equivalent (OME), is generated in which tumour cells are integrated in order to be able to analyse tumourigenesis and tumour growth in the environment of healthy oral mucosa just as the tumour development would take place in vivo. For this primary fibroblasts, primary keratinocytes and tumour cells were cultured on a matrix of decellularized, porcine, small intestinal submucosa (SIS/MUC). For this FaDu cells were transduced with the lentivirus RFP to be able to distinguish the immigrated cells from healthy cells. The transduction was successful. It was possible to achieve a fluorescence of the cells still cultivated in cell culture dishes. However, the fluorescent cells could no longer be detected in the fixed tissue sections. For the tumour model three different forms of application of the tumour cells on the OMEs have been tested. The application of cell-spots, spheroids or cell mixtures of primary keratinocytes and FaDu tumour cells in previously cultivated OME. The application of spots or spheroids should initiate tumour cell growth even in the environment of healthy tissue. This would enable the in vitro analysation of the area of healthy and pathological tissue in one model. Therefore, the optimal concentration of tumour cells, which is necessary for the tumour development, and the most suitable application method are to be determined to be able to apply a suitable reproducible tumour model. The models were analysed histologically and immunohistochemically, and the results were correlated with determined TEER values. In this work, the application of spots or spheroids did not achieve tumour growth in the environment of healthy oral mucosa. The cells were not responsive to the adjacent stratum corneum on the highly pronounced horn layer of the OME and no migration into the underlying tissue was possible. However, by applying a cell mixture of varying mixing ratios of primary keratinocytes and tumour cells of the FaDu cell line, it has been possible to initiate 3D tumour growth of different malignant stages. The smaller the mixing ratio and the higher the number of FaDu tumour cells, the more pronounced have been the morphological signs of tumour formation. Even if it was no longer possible to mimic a combination of healthy and pathological tissue in a model, clear pathological, malignant tumour models could be generated at least after histological and immunohistochemical investigations. The tumour models consistently showed cellular- and nuclearpleomorphisms, atypical and increased suprabasal mitoses, disruption of normal tissue architecture, the formation of intercellular bridges, single cell dyskeratosis and cornification buds, as well as sites of disruption of the basement membrane and invasion of tumour cells into the underlying lamina propria. All these are clear signs of malignant growth. The results of the TEER value measurement were also consistent with the morphological developments of the models. Thus, the TEER values of the control models rose consistently, which indicates a significant development of continuous tissue. In contrast, the TEER values over the course of time of the tumour models, in which the basal membrane and thus the continuity of the tissue was broken, fell rapidly or were in a constantly low range. The success of the establishment of this reliably reconstructable 3D, in vitro generated tumour model, which is very close to the in vivo situation of a squamous cell carcinoma, offers the science a very good opportunity to carry out further studies on tumour growth. In addition, the further development and improvement of promising, novel chemotherapeutic and radiological therapy methods can be considerably advanced, thereby improving the chances of recovery with fewer side effects for the patient and achieving an increased quality of life.

Orientador: Gustavo Franco Barbosa / Resumo: Há décadas, a engenharia de tecidos passou a ser considerada em diversas aplicações, um tratamento médico adequado, devido suas excelentes vantagens, além da escassez de órgãos e disponibilidade de tecidos para serem transplantados. Conhecida como regeneração de novos tecidos, esse ramo da engenharia biomédica fundamentada nos conhecimentos de Biologia, Química e Física, torna-se uma grande alternativa quando tratamentos farmacêuticos convencionais não são mais aplicáveis, utilizando-se de três tipos básicos de ferramentas: célula, scaffolds e fator de crescimento. Dessa forma, esse trabalho tem como propósito principal a manufatura de scaffolds, utilizando a tecnologia de impressão 3D a partir de polímeros termoplásticos biodegradáveis e fosfatos de cálcio (em escala micrométrica), com o objetivo de se obter estruturas 3D complexas e porosas que apresentem propriedades mecânicas adequadas (em relação a ossos) e interconectividade estruturada entre os poros. Com os modelos 3D dos scaffolds projetados, e a seleção e preparação dos materiais envolvidos, foram realizados ajustes de parâmetros para o processamento dos scaffolds e posterior fabricação dos mesmos, mediante o uso da tecnologia de manufatura aditiva com bioimpressora de microextrusão que utiliza sistema de distribuição pneumático para extrusão contínua do material. Por fim os scaffolds foram caracterizados por técnica de análise de propriedade mecânica por ensaio de compressão e as amostras avaliadas pelo método de M... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: For decades, tissue engineering has come to be considered in several applications, an adequate medical treatment, due to its excellent advantages, in addition to the scarcity of organs and the availability of tissues to be transplanted. Known as regenerating of new tissues, this branch of biomedical engineering grounded in the knowledge of biology, chemistry and physics, becomes a great alternative when conventional pharmaceutical treatments are no longer applicable, using three basic types of tools: cell, scaffolds and growth factor. Thus, the main purpose of this work is the manufacture of scaffolds, using the technology of 3D printing from biodegradable thermoplastic polymers and calcium phosphates (in micrometric scale), with the objective of obtaining complex and porous 3D structures that present properties mechanical (in relation to bones) and structured interconnectivity between the pores. With the 3D models of the scaffolds designed, and the selection and preparation of the materials involved, adjustments were made to the processing parameters of the scaffolds and their subsequent manufacture, using the technology of additive manufacturing with microextrusion bioprinter that uses pneumatic distribution system for continuous extrusion of the material. Finally, the scaffolds were characterized by technique of mechanical property analysis by compression test and the samples evaluated by Scanning Electron Microscopy (SEM) method. / Mestre

Thesis (M.S.) -- Mississippi State University. Department of Agricultural and Biological Engineering. / Title from title screen. Includes bibliographical references.

<p>A novel strategy for synthesising segmented poly(urethane urea) (PUU) without using a chain extender but nevertheless with the opportunity to vary the hard segment content has been developed. The strategy is based on amine formation from isocyanate upon reaction with water. By adding a dissolved soft segment to an excess of diisocyanate followed by the addition of water in the gas phase, amines are formed <i>in situ</i>. Urea linkages are then formed when these amines react with the excess of isocyanate groups. The gas phase addition facilitates addition in a slow and continuous manner. The hard segment content can easily altered by varying the diisocyanate/soft segment ratio. Even though the strategy is shown to be applicable to different diisocyanates, the focus has been on the potentially biodegradable methyl-2,6-diisocyanatehexanoate (LDI) and 1.4-butanediisocyanate (BDI) and various well known biodegradable polyesters and polycarbonates. </p><p>All the synthesised materials exhibited pronounced phase separation and hydrogen bonding within the hard domains. However, a major increase in hydrogen bonding strength was seen when a symmetric diisocyanate was used instead of an asymmetric. Based on FTIR measurements, PUUs with BDI and a polydisperse hard segment can exhibit the same degree of phase separation and hydrogen bonding as the monodisperse product.</p><p>The elastic properties of this new group of PUUs were exceptional with an elongation at break from 1600% to almost 5000% and the elastic modulus could be varied from a few MPa up to a couple of hundreds. </p><p>Hydrolytic degradation was greater in the polyester-based than in the polycarbonate-based PUUs due to the more reactive ester bonds. Low mass loss but a considerable loss in molecular weight was seen in the polyester PUUs. The tensile strength decreased dramatically due to the loss of strain hardening.</p><p>An MTT seeding assay using human fibroblasts and an in vivo biocompatibility study were performed and no signs of cytotoxicity were seen and the inflammatory response was comparable to other inert polymers.</p><p>A biodegradable PUU with properties that can be tailored through an easy synthesis is here presented. </p>

Peripheral nerve injuries are often associated with significant loss of nervous tissue leading to poor restoration of function following repair of injured nerves. Although the injury gap could be bridged by autologous nerve graft, the limited access to donor material and additional morbidity such as loss of sensation and scarring have prompted a search for biosynthetic nerve transplants. The present thesis investigates the effects of a synthetic matrix BD™ PuraMatrix™ peptide (BD)hydrogel, alginate/fibronectin gel and fibrin glue combined with cultured rat Schwann cells or human bone marrow derived mesenchymal stem cells (MSC) on neuronal regeneration and muscle recovery after peripheral nerve injury in adult rats. In a sciatic nerve injury model, after 3 weeks postoperatively, the regenerating axons grew significantly longer distances within the conduits filled with BD hydrogel if compared with the alginate/fibronectin gel. The addition of rat Schwann cells to the BD hydrogel drastically increased regeneration distance with axons crossing the injury gap and entering into the distal nerve stump. However, at 16 weeks the number of regenerating spinal motoneurons was decreased to 49% and 31% in the BD hydrogel and alginate/fibronectin groups respectively. The recovery of the gastrocnemius muscle was also inferior in both experimental groups if compared with the nerve graft. The addition of the cultured Schwann cells did not further improve the regeneration of motoneurons and muscle recovery. The growth-promoting effects of the tubular conduits prepared from fibrin glue were also studied following repair of short and long peripheral nerve gaps. Retrograde neuronal labeling demonstrated that fibrin glue conduit promoted regeneration of 60% of injured sensory neurons and 52% of motoneurons when compared with the autologous nerve graft. The total number of myelinated axons in the distal nerve stump in the fibrin conduit group reached 86% of the nerve graft control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89%, respectively. When a fibrin conduit was used to bridge a 20 mm sciatic nerve gap, the weight of gastrocnemius muscle reached only 43% of the nerve graft control. The morphology of the muscle showed a more atrophic appearance and the mean area and diameter of fast type fibres were significantly worse than those of the corresponding 10 mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. The combination of fibrin conduit with human MSC and daily injections of cyclosporine A enhanced the distance of regeneration by four fold and the area occupied by regenerating axons by three fold at 3 weeks after nerve injury and repair. In addition, the treatment also significantly reduced the ED1 macrophage reaction. At 12 weeks after nerve injury the treatment with cyclosporine A alone or cyclosporine A combined with hMSC induced recovery of the muscle weight and the size of fast type fibres to the control levels of the nerve graft group. In summary, these results show that a BD hydrogel supplemented with rat Schwann cells can support the initial phase of neuronal regeneration across the conduit. The data also demonstrate an advantage of tubular fibrin conduits combined with human MSC to promote axonal regeneration and muscle recovery after peripheral nerve injury.

A novel strategy for synthesising segmented poly(urethane urea) (PUU) without using a chain extender but nevertheless with the opportunity to vary the hard segment content has been developed. The strategy is based on amine formation from isocyanate upon reaction with water. By adding a dissolved soft segment to an excess of diisocyanate followed by the addition of water in the gas phase, amines are formed in situ. Urea linkages are then formed when these amines react with the excess of isocyanate groups. The gas phase addition facilitates addition in a slow and continuous manner. The hard segment content can easily altered by varying the diisocyanate/soft segment ratio. Even though the strategy is shown to be applicable to different diisocyanates, the focus has been on the potentially biodegradable methyl-2,6-diisocyanatehexanoate (LDI) and 1.4-butanediisocyanate (BDI) and various well known biodegradable polyesters and polycarbonates. All the synthesised materials exhibited pronounced phase separation and hydrogen bonding within the hard domains. However, a major increase in hydrogen bonding strength was seen when a symmetric diisocyanate was used instead of an asymmetric. Based on FTIR measurements, PUUs with BDI and a polydisperse hard segment can exhibit the same degree of phase separation and hydrogen bonding as the monodisperse product. The elastic properties of this new group of PUUs were exceptional with an elongation at break from 1600% to almost 5000% and the elastic modulus could be varied from a few MPa up to a couple of hundreds. Hydrolytic degradation was greater in the polyester-based than in the polycarbonate-based PUUs due to the more reactive ester bonds. Low mass loss but a considerable loss in molecular weight was seen in the polyester PUUs. The tensile strength decreased dramatically due to the loss of strain hardening. An MTT seeding assay using human fibroblasts and an in vivo biocompatibility study were performed and no signs of cytotoxicity were seen and the inflammatory response was comparable to other inert polymers. A biodegradable PUU with properties that can be tailored through an easy synthesis is here presented.