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Tissue engineering advancements have seen a multitude of findings in several disciplines, including cell biology, imaging, characterization of cell–material and cell–cell interactions, and also novel biomaterial research. The main aim of tissue engineering, however, remains as a tool to restore, maintain, or improve defective tissue functions. The paradigm of this concept is threefold: (1) Isolation of cells, (2) Seeding of cells into the appropriate 3D scaffolds, and (3) Providing the appropriate growth factors and physical and mechanical conditions in-vitro thereby mimicking the native conditions conducive for cell and tissue growth. The development of the 3D scaffold or matrix is by far the most challenging aspect wherein the choice of the scaffold material, its biocompatibility, cell–material interactions, its biodegradation and bioresorption properties, all play a major role. Polymers have been a mainstay as scaffold material for such applications. Both synthetic and natural polymers have been used as matrices for cell and tissue growth. The main aim in development of polymeric scaffold for tissue engineering is that it should resemble the properties of the tissues native extracellular matrix. A lot of advancements have been made in the last 10 years in the area of polymers used for tissue engineering applications and this chapter aims to provide a comprehensive coverage of the field.

The field of additive manufacturing is rapidly growing that aims in the development of sophisticated construct for in vitro modeling and tissue regeneration, offering hope of bridging the gap between organ shortage and transplantation need. The recent advances in this field is the ability of printing biocompatible material and the most importantly to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues and organs. The field of bioprinting has laid a milestone in various disciplines such as tissue engineering, regenerative medicine and pharmaceutics. In particular, the creation of vascularized tissue remained a principle challenge in the field of tissue engineering. Compared to the non-biological printing such as the polymeric scaffold printing, the process of bioprinting involves a lot of complexities. Some of the critical challenges involve the type of material, cell, growth factor, cell viability and many more. These entanglements are being addressed by the amalgamation of different technologies like engineering, material science, cell biology, physics and medicine. Here we review on the advancement in the 3D bioprinting process and the commonly used material for bioprinting. We focus on the properties of an ideal bioink and the cell response to the printed scaffold. Finally, we conclude with the current challenges and the future perspective of 3D organ printing.

Molecularly imprinted polymers (MIPs) are biomimetic recognition elements developed for affinity chromatography, sensorics, and potential substitutes of antibodies in therapy. They are prepared by polymerizing one to six monomers in the presence of the target analyte followed by the formation of “paratope-analog” binding sites by the removal of the template from the polymeric scaffold. Electrochemical methods allow for the straightforward synthesis by electropolymerization, template removal by electro-elution, and readout of molecularly imprinted polymers. A wide range of MIP-based electrochemical sensors for low-molecular weight substances, biopolymers as well as cells and viruses have been developed within the past 20 years. All types of nanomaterials have been successfully integrated into the MIP-layer, to enhance the sensitivity. Quantum dots are mostly used in electrochemical sensing to increase the electroactive surface and found limited application as “active” components in (photo) electrochemical MIP-sensors. Integration of quantum dots requires sophisticated preparation procedures, and it is seldom justified by the analytical performance in real samples.

Fibrinogen is a large glycoprotein, synthesized primarily in the liver. With a normal plasma concentration of 1.5-3.5 g/L, fibrinogen is the most abundant blood coagulation factor. The final stage of blood clot formation is the conversion of soluble fibrinogen to insoluble fibrin, the polymeric scaffold for blood clots that stop bleeding (a protective reaction called hemostasis) or obstruct blood vessels (pathological thrombosis). Fibrin is a viscoelastic polymer and the structural and mechanical properties of the fibrin scaffold determine its effectiveness in hemostasis and the development and outcome of thrombotic complications. Fibrin polymerization comprises a number of consecutive reactions, each affecting the ultimate 3D porous network structure. The physical properties of fibrin clots are determined by structural features at the individual fibrin molecule, fibrin fiber, network, and whole clot levels and are among the most important functional characteristics, enabling the blood clot to withstand arterial blood flow, platelet-driven clot contraction, and other dynamic forces. This chapter describes the molecular structure of fibrinogen, the conversion of fibrinogen to fibrin, the mechanical properties of fibrin as well as its structural origins and lastly provides evidence for the role of altered fibrin clot properties in both thrombosis and bleeding.

Computer-aided wet-spinning (CAWS) has emerged in the past few years as a hybrid fabrication technique coupling the advantages of additive manufacturing in controlling the external shape and macroporous structure of biomedical polymeric scaffold with those of wet-spinning in endowing the polymeric matrix with a spread microporosity. This book chapter is aimed at providing a detailed description of the experimental methods developed to fabricate by CAWS polymeric scaffolds with a predefined external shape and size as well as a controlled internal porous structure. The protocol for the preparation of poly(e-caprolactone)-based scaffolds with a predefined pore size and geometry will be reported in detail as a reference example that can be followed and simply adapted to fabricate other kinds of scaffold, with a different porous structure or based on different biodegradable polymers, by applying the processing parameters reported in relevant tables included in the text.

Bone tissue is the structural component of the body, which allows locomotion, protects vital internal organs, and provides the maintenance of mineral homeostasis. Several bone-related pathologies generate critical-size bone defects that our organism is not able to heal spontaneously and require a therapeutic action. Conventional therapies span from pharmacological to interventional methodologies, all of them characterized by several drawbacks. To circumvent these effects, tissue engineering and regenerative medicine are innovative and promising approaches that exploit the capability of bone progenitors, especially mesenchymal stem cells, to differentiate into functional bone cells. So far, several materials have been tested in order to guarantee the specific requirements for bone tissue regeneration, ranging from the material biocompatibility to the ideal 3D bone-like architectural structure. In this review, we analyse the state-of-the-art of the most widespread polymeric scaffold materials and their application in in vitro and in vivo models, in order to evaluate their usability in the field of bone tissue engineering. Here, we will present several adopted strategies in scaffold production, from the different combination of materials, to chemical factor inclusion, embedding of cells, and manufacturing technology improvement.

Pancreatic-islet transplantation is a safe and noninvasive therapy for type 1 diabetes. However, the currently applied site for transplantation, ie, the liver, is not the optimal site for islet survival. Because the human body has shortcomings in providing an optimal site, artificial transplantation sites have been proposed. Such an artificial site could consist of a polymeric scaffold that mimics the pancreatic microenvironment and supports islet function. Recently, remarkable progress has been made in the technology of engineering scaffolds. The polymer-islet interactions, the site of implantation, and scaffold prevascularization are critical factors for success or failure of the scaffolds. This article critically reviews these factors while also discussing translation of experimental studies to human application as well as the steps required to create a clinically applicable prevascularized, retrievable scaffold for implantation of insulin-producing cells for treatment of type 1 diabetes mellitus. Important advances have been made in the design and testing of polymeric scaffolds for pancreatic islet transplantation, but some challenges remain to be solved before human application.

Reconstruction of large bone defects resulting from trauma, neoplasm, or infection is a challenging problem in reconstructive surgery. The need for bone grafting has been increasing steadily partly because of our enhanced capability to salvage limbs after major bone loss. Engineered bone graft substitutes can have advantages such as lack of antigenicity, high availability, and varying properties depending on the applications chosen for use. These favorable attributes have contributed to the rise of scaffold-based polymeric tissue regeneration. Critical components in the scaffold-based polymeric regenerative engineering approach often include 1. The existence of biodegradable polymeric porous structures with properties selected to promote tissue regeneration and while providing appropriate mechanical support during tissue regeneration. 2. Cellular populations that can influence and enhance regeneration. 3. The use of growth and morphogenetic factors which can influence cellular migration, differentiation and tissue regeneration in vivo. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and their ability to produce biocompatible degradation products. This paper presents an overview of polymeric scaffold-based bone tissue regeneration and reviews approaches as well as the particular roles of biodegradable polymers currently in use.

The limitations of newly synthesized biodegradable stents are low mechanical strength, fracture stiffness, and fast degradability of the polymers. A cylindrical polymeric scaffold was proposed in c...

Biodegradable polymeric scaffolds have received much attention in tissue engineering as they provide a spatial and temporal environment for cell regeneration. The scaffold can be defined as “any material, natural or artificial that comprises of entire or portion of a living structure or biomedical device which performs, extends or substitutes a natural function”. Biomaterials based scaffolds are projected to interact with living systems and to treat, augment, assess and substitute any function, tissue, and organ of the body. Tissue engineering aims to facilitate the growth and replace the diseased or damaged tissue by using the combination of bioactive molecules, cells, and biomaterials. Many clinical studies were carried out to repair or replace tissue in the human body such as damaged or diseased tissue using autografts, xenografts or allografts (i.e. donor graft tissue). But a major drawback of these treatments is a shortage of donor site or donor rejection of grafts, morbidity, donor site pain, the transmission of disease, the possibility of harmful immune responses and the volume of donor tissue. In the last two decades, rapid progress has been seen in the emerging field of tissue regeneration and tissue engineering.

The fabrication of a dual-functional drug-containing porous polymeric scaffold by layer-by-layer surface modification involving citrate-stabilized gold nanoparticles and cisplatin molecules is being reported. These scaffolds were characterized by electron microscopy and X-ray photoelectron spectroscopy. The capability of the scaffolds to release hydrated cisplatin in a slow and sustained manner over two days is established. Most importantly, the scaffolds turn nontoxic and cell-friendly after drug release, thus allowing the noncancerous fibroblast cells to adhere and proliferate (from 5000 cells to 16,000 cells in 6 days), becoming a potential solution toward an effective drug-carrying scaffold for volume-filling applications. The scaffold-mediated cancer cell killing and fibroblast cell proliferation were confirmed by fluorescence microscopy imaging, flow cytometry, and cell proliferation assays. We surmise that such a dual-purpose (drug-delivery and volume-filler) scaffold could help avoid the multiple surgical interventions needed for tumor surgery and cosmetic corrections. To the best of our knowledge, this is the first example of scaffolds with such a dual functionality which gets manifested in a sequential manner.

152 p. A degradable multi-functional scaffold was developed to provide mechanical support for tissue regeneration and to deliver various genes/ proteins/ drugs with respective release profile at different stages of implantation. An indirect binding approach with three-dimensional printing (3DP) was accomplished in this study to solve the limitation of solvent printing for polymeric scaffold. This method enables the printing of different polymers with water and the fabrication of highly versatile scaffold for either soft or hard tissue implantation. MASTER OF ENGINEERING (SCBE)

Tissue-engineered vascular grafts hold great promise in many clinical applications, especially in pediatrics wherein growth potential is critical. A continuing challenge, however, is identification of optimal scaffold parameters for promoting favorable neovessel development. In particular, given the countless design parameters available, including those related to polymeric microstructure, material behavior, and degradation kinetics, the number of possible scaffold designs is almost limitless. Advances in computationally modeling the growth and remodeling of native blood vessels suggest that similar simulations could help reduce the search space for candidate scaffold designs in tissue engineering. In this study, we meld a computational model of in vivo neovessel formation with a surrogate management framework to identify optimal scaffold designs for use in the extracardiac Fontan circulation while comparing the utility of different objective functions. We show that evolving luminal radius and graft compliance can be matched to that of the native vein by the end of the simulation period with judicious combinations of scaffold parameters, although the inability to match these metrics at all times reveals constraints engendered by current materials. We emphasize further that there is yet a need to examine additional metrics, and combinations thereof, when seeking to optimize functionality and reduce the potential for adverse outcomes. IMPACT STATEMENT: Tissue-engineered vascular grafts have considerable promise for treating myriad conditions, and multiple designs are now in FDA-approved trials. Nevertheless, the search continues for the optimal design of the underlying polymeric scaffold. We present a novel melding of a computational model of vascular adaptation and a formal method of optimization that can aid in identifying optimal design parameters, with potential to save development time and costs while improving clinical outcomes.

Current neural tissue engineering strategies involve the development and application of neural tissue constructs produced by using an anisotropic polymeric scaffold. This study reports a scaffold-free method of tissue engineering to create a tubular neural tissue construct containing unidirectional neuron bundles. The surface patterning of a thermoresponsive culture substrate and a coculture system of neurons with patterned astrocytes can provide an anisotropic structure and easy handling of the neural tissue construct without the use of a scaffold. Furthermore, using a gelatin gel-coated plunger, the neuron bundles can be laid out in the same direction at regulated intervals within multilayered astrocyte sheets. Since the 3D tissue construct is composed only by neurons and astrocytes, they can communicate physiologically without obstruction of a scaffold. The medical benefits of scaffold-free tissue generation provide new opportunities for the development of human cell-based tissue models required to better understand the mechanisms of neurodegenerative diseases. Therefore, this new tissue engineering approach may be useful to establish a technology for regenerative medicine and drug discovery using the patient's own neurons.

This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed.

Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro-dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal "polyzymes," is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media. The therapeutic potential of these polyzymes is demonstrated by the transformation of a nontoxic prodrug to an anticancer drug (mitoxantrone), leading to the cancer cell death in vitro.

Presently available long-acting reversible female contraceptive implants are said to be an effective way of preventing unintended pregnancy. Unacceptable side effects attributed by these contraceptive implants act as a major drawback for the practitioners. These problems pave the way for the development of a new form of long-acting non-hormonal female contraceptive implant, especially in the developing countries. PCL-DA: PEG-DA polymeric scaffold is grafted with Styrene Maleic Anhydride (SMA) based hydrogel, and their physicochemical, thermal and biological parameters are being explored for developing a bio-degradable form of the non-hormonal intrauterine contraceptive implant. With the fixed ratio of PEG-DA: PCL-DA polymer, SMA hydrogel was added at four different concentrations to determine the optimum concentration of SMA hydrogel for the development of a promising long-acting biodegradable intrauterine contraceptive implant. Structural elucidation of the polymers was confirmed using 1H and 13C NMR spectroscopic analyses. The physiochemical characterization report suggests that SMA hydrogel interacts with the PCL-DA: PEG-DA polymeric scaffold through intermolecular hydrogen bonding interaction. The in-vitro spermicidal activity of the polymeric scaffold increases when the concentration of SMA based hydrogel in the polymer samples is increased without showing any significant toxicological effects. From the study results, it may be concluded that SMA hydrogel grafted PCL-DA: PEG-DA scaffold can be developed as intra-uterine biodegradable non-hormonal female contraceptive implant due to its excellent bio-compatibility and spermicidal activity.

Myocardial remodeling, including ventricular dilation and wall thinning, is an important pathological process caused by myocardial infarction (MI). To intervene in this pathological process, a new type of cardiac scaffold composed of a thermoset (poly-[glycerol sebacate], PGS) and a thermoplastic (poly-[e-caprolactone], PCL) is directly printed by employing fused deposition modeling 3D-printing technology. The PGS-PCL scaffold possesses stacked construction with regular crisscrossed filaments and interconnected micropores and exhibits superior mechanical properties. In vitro studies demonstrate favorable biodegradability and biocompatibility of the PGS-PCL scaffold. When implanted onto the infarcted myocardium, this scaffold improves and preserves heart function. Furthermore, the scaffold improves several vital aspects of myocardial remodeling. On the morphological level, the scaffold reduces ventricular wall thinning and attenuated infarct size, and on the cellular level, it enhances vascular density and increases M2 macrophage infiltration, which might further contribute to the mitigated myocardial apoptosis rate. Moreover, the flexible PGS-PCL scaffold can be tailored to any desired shape, showing promise for annular-shaped restraint device application and meeting the demands for minimal invasive operation. Overall, this study demonstrates the therapeutic effects and versatile applications of a novel 3D-printed, biodegradable and biocompatible cardiac scaffold, which represents a promising strategy for improving myocardial remodeling after MI.

WOS: 000460303600005 PubMed ID: 29694659 AIM: To design a novel, polyvinyl alcohol (PVA)-based polymeric scaffold that permits the controlled release of insulin-like growth factor 1 (IGF-1) /bone morphogenetic protein (BMP)-2 following intervertebral disc administration. MATERIAL and METHODS: The drug delivery system was composed of two different solutions that formed a scaffold within seconds of coming into contact with each other. Swelling, pH, and temperature tests and analysis of the controlled release of growth factors (GFs) from this system were performed. The release kinetics of the GFs were determined through enzyme-linked immunosorbent assay (ELISA). Cell proliferation and viability were monitored with microscopy and analyzed using an MTT assay and acridine orange/propidium iodide (AO/PI) staining. Chondroadherin (CHAD), hypoxia inducible factor-1 alpha (HIF-1 alpha), and collagen type II (COL2A1) gene expressions were determined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis to show the effects of IGF-1/BMP-2 administration on annulus fibrosus cell (AFC)/nucleus pulposus cell (NPC) cultures. For the statistical evaluation of the obtained data, experimental groups were compared with a post hoc Tukey's test following an analysis of variance. RESULTS: The scaffold allowed for the controlled release of IGF-1 and BMP-2 in different time intervals. It was observed that as the application time increased, the number of cells and the degree of extracellular matrix development increased in AFC/NPC cultures. AO/PI staining and an MTT analysis showed that cells retained their specific morphology and continued to proliferate. It was observed that HIF-1 alpha and CHAD expression increased in a time-dependent manner, and no COL2A1 expression in the AFC/NPC cultures was observed. CONCLUSION: The designed scaffold may be used as an alternative method for intervertebral disc administration of GFs after further in vivo studies. Such prototype scaffolds may be an innovative technology in targeted drug therapies after reconstructive neurosurgical interventions.

In vivo development of a neovessel from an implanted biodegradable polymeric scaffold depends on a delicate balance between polymer degradation and native matrix deposition. Studies in mice suggest that this balance is dictated by immuno-driven and mechanotransduction-mediated processes, with neotissue increasingly balancing the hemodynamically induced loads as the polymer degrades. Computational models of neovessel development can help delineate relative time-dependent contributions of the immunobiological and mechanobiological processes that determine graft success or failure. In this paper, we compare computational results informed by long-term studies of neovessel development in immuno-compromised and immuno-competent mice. Simulations suggest that an early exuberant inflammatory response can limit subsequent mechano-sensing by synthetic intramural cells and thereby attenuate the desired long-term mechano-mediated production of matrix. Simulations also highlight key inflammatory differences in the two mouse models, which allow grafts in the immuno-compromised mouse to better match the biomechanical properties of the native vessel. Finally, the predicted inflammatory time courses revealed critical periods of graft remodeling. We submit that computational modeling can help uncover mechanisms of observed neovessel development and improve the design of the scaffold or its clinical use.

The advent of fully bioresorbable stent technology and specifically the ABSORB™, a bioresorbable vascular scaffold (BVS) stent, is heralded as breakthrough technology in the current era of percutaneous coronary interventions. This article reviews the current understanding of this technology along with the clinical evidence from trials and registries of ABSORB BVS that included patients with both simple as well as more complex "real-world" coronary lesions. In addition, considering the current limitations of this device-mostly associated with the mechanical properties of the polymeric scaffold structure-a review of guidelines on successful implantation of the ABSORB BVS is presented. Although expert feedback suggests extensive use of this device in routine clinical practice outside the United States despite a paucity of data on long-term safety in this setting, attention to procedural details and implantation technique is obligatory to achieve optimal clinical outcomes.

Oligoanilines1 are an interesting class of compounds, attractive as a means to impart electroactivity and stimuli responsiveness into a wide array of polymeric scaffolds. As model compounds of polyaniline (PANI), oligoaniline containing copolymers feature superior solubility, processability, and tunability when compared to their parent homopolymer, while retaining much of PANI?s functional capabilities. The absorption peak of the exciton-type transition increased in intensity until reaching a maximum, indicating the oligoaniline segment was in the emeraldine base (EB), with the AT segment containing one quinoid ring. With further oxidation, both absorption peaks decreased in intensity. The peak at 580 nm proceeded to redshift to a maximum of 645 nm, after which it remained unchanged indicating full oxidation to the pernigraniline base (PNB) with the AT segment containing two quinoid rings.

Controlling biological growth within a cell-laden polymeric scaffold is a critical challenge in the tissue engineering community. Indeed, construct growth must often be balanced with scaffold degradation and is often coupled to varying degrees of deformation that originate from swelling, external forces and the effects of confinement. These factors have been shown to affect growth in many ways, but to date, our understanding is mostly qualitative. While cell sensing, molecular transport and scaffold/tissue interactions are believed to be important players, it will be critical to quantify, predict and control these effects in order to eventually optimize tissue growth in the laboratory. The aim of this paper was thus to provide a theoretical framework to better understand how the scaffold-mediated mechanisms of transport, deposition (and possibly degradation) and elasticity affect the overall growth of a tissue subjected to finite deformations. We propose a formulation in which the macroscopic evolutions in tissue size, density as well as the appearance of residual stresses can be directly related to changes in internal composition by considering three fundamental principles: mechanical equilibrium, chemical equilibrium and molecular incompressibility. The resulting model allows us to pay particular attention to features that are critical to the interaction between growth and deformation: osmotic pressure and swelling, the strain mismatch between old and newly deposited material as well as the mechano-sensitive cell-mediated production. We show that all of these phenomena may indeed strongly affect the overall growth of a construct under finite deformations.

Stemming from the first pioneering works carried out in the late 1990s, a fast-growing body of scientific literature has been focused on the investigation of various additive manufacturing techniques (e.g., fused deposition modeling and stereolithography) for the development of customized polymeric devices for different biomedical applications, such as tissue engineering scaffolds and permanent endoprostheses. In addition, the combination of additive manufacturing with other polymer processing techniques has been investigated as a powerful tool for the enhancement of polymeric scaffold structural and functional features including resolution, surface topography, local porosity, and multiscale architectural design. This chapter is aimed at providing a comprehensive overview of the current progress integrating additive manufacturing and electrofluidodynamic techniques. The main technological aspects of additive manufacturing as a biofabrication approach to developing tissue-engineered constructs are first outlined by presenting and discussing different strategies involving the processing of cell-laden materials or the fabrication of scaffolds able to steer cell behavior through structural stimuli. The different technological solutions developed to integrate additive manufacturing and electrofluidodynamics are then analyzed through an overview of significant literature aimed at imparting nanoscale features to microarchitectures or patterning nanostructures (i.e., nanofibers or nanoparticles) into 3D-layered architectures.

Tissue engineering creates biological tissues that aim to improve the function of diseased or damaged tissues such as the cornea (the main refractive component of the eye). Traditional tissue engineering strategies employ a “top-down” approach, in which cells are seeded on a polymeric scaffold that they then populate and create the appropriate extracellular matrix (ECM) often with the aid of perfusion, growth factors and/or mechanical stimulation. However, in highly organised tissues, such as the cornea, top-down approaches have difficulty recreating intricate but necessary microstructural features. With the desire to create more complex corneal tissues with features such as anisotropic hierarchical molecular assemblies, appropriate mechanical properties, cell binding motifs and corneal specific morphology, we are developing tissue engineering techniques that are moving away from the traditional top-down approach and instead focusing on building modular micro-tissues with repeated functional units which facilitate a bottom-up approach. Here we report on the success and shortcomings of both top-down and bottom-up approaches to creating engineered corneal tissues. Specifically, we will discuss recent work demonstrating the importance of engineering corneal ECM with appropriate levels of tissue compliance using a top-down approach. We will then highlight a bottom-up approach, which focuses on fabricating discreet bio-prosthetic ECM building blocks (corneal lamellae) with specific micro-architectural features derived solely from human corneal keratocytes under serum free conditions using enzyme responsive templates. These building blocks will then be used to generate a whole cornea whilst maintaining the intricate architecture and complexity of native corneal ECM.

International audience; Increasing numbers of requests for transplantable organs and their scarcity has led to a pressing need to find alternative solutions to standard transplantation. An appealing but challenging proposal came from the fields of tissue engineering and regenerative medicine, the purpose of which is to build tissues/organs from scratch in the laboratory and use them as either permanent substitutes for direct implantation into the patient's body, or as temporary substitutes to bridge patients until organ regeneration or transplantation. Using bioartificial constructs requires administration of immunosuppressant therapies to prevent rejection by the recipient. Microencapsulation has been identified as promising technology for immunoisolating biological materials from immune system attacks by the patient. It is based on entrapping cellular material within a spherical semipermeable polymeric scaffold. This latter defines the boundary between the internal native-like environment and the external "aggressive" one. The scaffold thus acts like a selective filter that makes possible an appropriate supply of nutrients and oxygen to the cellular constructs, while blocking the passage for adverse molecules. Alginate, which is a natural polymer, is the main biomaterial used in this context. Its excellent properties and mild gelation ability provide suitable conditions for supporting viability and preserving the functionalities of the cellular-engineered constructs over long periods. Although much remains to be done before bringing microencapsulated constructs into clinical practice, an increasing number of applications for alginate-based microencapsulation in numerous medical areas confirm the considerable potential for this technology in providing a cure for transplant in patients that excludes immunosuppressive therapies.

The analysis of bioresorbable scaffolds (BRSs) by optical coherence tomography (OCT) requires a dedicated methodology, as the polymeric scaffold has a distinct appearance and undergoes dynamic structural changes with time. The high resolution of OCT allows for the detailed assessment of scaffold implantation, rupture, discontinuity, and strut integration. OCT does not provide reliable information on the extent of scaffold degradation, as it cannot differentiate between polylactide polymer and the provisional matrix of proteoglycan formed by connective tissue. Three-dimensional OCT reconstruction can aid in the evaluation of BRS in special scenarios such as overlapping scaffold segments and bifurcations.

The occurrence of dysfunctional aortic valves is increasing every year, and current replacement heart valves, although having been shown to be clinically successful, are only short-term solutions and suffer from many agonizing long-term drawbacks. The tissue engineering of heart valves is recognized as one of the most promising answers for aortic valve disease therapy, but overcoming current shortcomings will require multidisciplinary efforts. The use of a polymeric scaffold to guide the growth of the tissue is the most common approach to generate a new tissue for an aortic heart valve. However, optimizing the design of the scaffold, in terms of biocompatibility, surface morphology for cell attachments and the correct rate of degradation is critical in creating a viable tissue-engineered aortic heart valve. This paper highlights the bioengineering strategies that need to be followed to construct a polymeric scaffold of sufficient mechanical integrity, with superior surface morphologies, that is capable of mimicking the valve dynamics in vivo. The current challenges and future directions of research for creating tissue-engineered aortic heart valves are also discussed.

BACKGROUND Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts.

The constantly expanding repository of novel polymers and stem cells has opened up new vistas in the field of cardiac tissue engineering. Successful regeneration of the complex cardiac tissue mainly centres on the appropriate scaffold material with topographical features that mimic the native environment. The integration of stem cells on these scaffolds is expected to enhance the regeneration potential. This review elaborates on the interplay of these vital factors in achieving the functional cardiac tissue. The recent advances in polymers, nanocomposites, and stem cells from different sources are highlighted. Special emphasis is laid on the clinical trials involving stem cells and the state-of-the-art materials to obtain a balanced perspective on the translational potential of this strategy.

Orientador: Maria Isabel Felisberti Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química Resumo: Este trabalho tem como objetivo a síntese, a caracterização e a aplicação de copolímeros anfifílicos triblocos e pentablocos, baseados em poli(L-lactídeo) (PLLA) e em poliéteres de óxido de etileno e óxido de propileno, PEO, PEO-b-PPO-b-PEO, PPO-b-PEO-b-PPO e PEO-ran-PPO, como biomateriais na forma de nanocompósitos e de arcabouços carreadores de fármacos. Os copolímeros foram sintetizados via polimerização por abertura de anel do L,L-lactídeo, utilizando-se poliéteres com distintas composições e arquiteturas como macroiniciadores. Estes copolímeros combinam as características antagônicas de seus blocos, como hidrofilicidade/hidrofobicidade e flexibilidade/rigidez. Além disso, os blocos das pontas de cadeia dos copolímeros, constituídos por PLLA, cristalizam e impedem a cristalização dos blocos poliéteres centrais. A hidrofilicidade dos copolímeros, avaliada em ensaios de intumescimento e molhabilidade em água, apresenta uma estreita relação com o teor de PEO nos materiais, podendo ser modulada por ambos: arquitetura e composição dos copolímeros. Ensaios de citotoxicidade revelaram a adesão e a proliferação celular sobre a superfície de filmes dos copolímeros. Valendo-se da natureza anfifílica desses copolímeros, nanocompósitos foram preparados pela dispersão de nanohidroxiapatita, uma carga hidrofílica. A dispersão da carga foi realizada em suspensão de benzeno, seguida de liofilização e termomoldagem por injeção em corpos de prova cilíndricos e retangulares. A fase hidrofílica dos copolímeros contribuiu de forma efetiva para a dispersão uniforme e para a adesão da carga à matriz polimérica. As propriedades mecânicas dos nanocompósitos foram determinadas por dois efeitos antagônicos associados à introdução de uma carga rígida de reforço e à diminuição do grau de cristalinidade, resultando em ligeiro aumento do módulo e da dureza. Por fim, arcabouços poliméricos anfifílicos foram eletrofiados na presença e na ausência de fármacos modelos hidrofílico e hidrofóbico. A natureza anfifílica dos copolímeros capacitou-os a encapsular ambos os fármacos, porém a eficiência de encapsulamento e o mecanismo de liberação dos fármacos em meio aquoso e a pH 7,4 mostraram-se dependentes principalmente da afinidade copolímero/fármaco. Os copolímeros, assim como seus nanocompósitos com nanohidroxiapatita e arcabouços carreadores de fármaco, apresentam potencial para aplicação como biomateriais, cujas propriedades podem ser amplamente moduladas para uma determinada aplicação Abstract: The purpose of this work is the synthesis, characterization and application of triblock and pentablock amphiphilic copolymers, based on poly(L-lactide) (PLLA) and polyethers of ethylene oxide and propylene oxide: PEO, PEO-b-PPO-b-PEO, PPO-b-PEO-b-PPO and PEO-ran-PPO, as nanocomposites and drug carrier scaffolds biomaterials. The copolymers were synthesized by ring-opening polymerization of L-lactide applying polyethers with distinct compositions and architectures as macroinitiators. These copolymers combine the antagonistic characteristics of their blocks, such as hydrophilicity/hydrophobicity and flexibility/stiffness. In addition, the end blocks of the copolymers, composed of PLLA, crystallize and prevent the central polyether blocks crystallization. The hydrophilicity of the copolymers was evaluated by water swelling and wettability tests, and it is closely related to the PEO content in the materials and can be modulated by copolymers both architecture and composition. Cytotoxicity assays revealed cell adhesion and proliferation on the copolymers films surfaces. Making use of the amphiphilic nature of these copolymers, nanocomposites were prepared by the dispersion of the hydrophilic filler nanohydroxyapatite. The filler dispersion was carried out in benzene suspensions, followed by freeze-dry and injection molding process, and cylindrical and rectangular specimens of the nanocomposites were obtained. The copolymers hydrophilic phase effectively contributed to the filler both uniform dispersion and adhesion to the polymeric matrix. The mechanical properties of the nanocomposites were determined by two antagonistic effects associated with the introduction of a rigid reinforcing filler and with the decrease of the crystallinity degree, resulting in a slight increase in elastic modulus and hardness. Finally, amphiphilic polymeric scaffolds were electrospun with and without the hydrophilic and hydrophobic model drugs addition. The amphiphilic nature of the copolymers enabled them to encapsulate both drugs; however the drugs encapsulation efficiency and release profile in aqueous medium at pH 7.4 were mainly dependent on the copolymer/drug affinity. The copolymers, as well as their nanocomposites with nanohydroxyapatite and drug carrier scaffolds, present the potential to be applied as biomaterials, whose properties can be widely modulated for a specific application Doutorado Físico-Química Doutora em Ciências FAPESP 2012/24821-0; 2010/17804-7

Among the various scaffold fabrication techniques, thermally induced phase separation (TIPS) is one of the most versatile methods to produce porous polymeric scaffold and it has been largely used for its capability to produce highly porous and interconnected scaffolds. The scaffold architecture can be closely controlled by varying the process parameters, including polymer type and concentration, solvent/non-solvent ratio and thermal history. TIPS technique has been widely employed, also, to produce scaffolds with a hierarchical pore structure and composite polymeric matrix/inorganic filler foams.

The foundation of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells. Tissue engineering utilizes living cells as engineering materials implanted, seeded or bio-plotted into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called scaffolds, are critical, both ex vivo and in vivo, to influence their own microenvironments. Scaffolds can serve the following purposes: allow cell attachment and migration, deliver and retain cells and biochemical factors, enable diffusion of vital cell nutrients or expressed products, exert certain mechanical and biological influences to modify the behaviour of the cell phase. Traditional tissue engineering strategies typically employ a “top-down” approach, in which cells are seeded on a biodegradable three dimensional monolithic polymeric scaffold. More recently they have been updated by a “bottom-up” approach, also known as modular tissue engineering; it is aimed to address the challenge of recreating bio-mimetic structures by designing structural micro-features to build modular tissues, used as building blocks to re-create larger ones. These two different approaches will require scaffolds with given characteristics obtainable by choosing different fabrication technologies. Conventional and innovative supercritical technologies for monolithic scaffold production or biopolymer micro/nano devices will be discussed in this chapter. Some examples of bone and cartilage tissue engineering produced by using modular scaffold will be also discussed, as well as the fabrication of artificial extracellular matrix for spatio-temporally delivery of biological and mechanical signal to address cell fate.