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Polycaprolactone (PCL) is a biodegradable polymer that is widely utilized for biomedical applications, as well as for environmentally sustainable packaging. The mechanisms driving PCL ...degradation appear to be overall variably documented and investigated, despite the potentially significant influence that aspects such as synthesis, end-group chemistry, molecular weight, and crystallinity, both before and after melt processing, may have on the behavior of the polymer over time. In this review, we identify mechanisms of PCL degradation across a range of mainly biomedical applications, exploring the role of the polymer structure and form, radical interactions, temperature, pH, enzymatic activity, and cellular phagocytosis. We examine how polymer chemistry has been used to alter PCL degradation rates and mechanisms, and present cases where such manipulations may affect the applications of PCL. We also comprehensively discuss the literature assessing the degradation of PCL in vitro and in vivo, and present a summary of the correlations and trends between the data. Significantly, our analysis identifies currently undescribed trends in PCL degradation. Namely, we observe that molecular weight decreases at a consistent rate regardless of the initial value, and does so at a linear rate in vitro and an exponential rate in vivo. Both mechanical properties and mass loss are strongly influenced by construct geometry and environmental conditions.
We further assess the current biomedical literature on the degradation of PCL copolymers and its composites. The formation of novel PCL copolymers or composites is often used to broaden the versatility and applicability of the polymer, although this approach is rarely explored beyond initial research. Novel biomaterials overall rarely emerge from research, with inherent issues such as the reproducibility of synthesis, manufacturing, or characterization methods and outcomes further impeding their translation. We conclude the review with a summary of the current state of the tailorability of PCL-based polymers and composites, and offer recommendations for the future research direction of the field.
To deepen understanding and hasten the development of treatments, cancer needs to be modelled more accurately in vitro; applying tissue-engineering concepts and approaches in this field could bridge ...the gap between two-dimensional studies and in vivo animal models.
Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of ...standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.
Lumbar fusion often remains the last treatment option for various acute and chronic spinal conditions, including infectious and degenerative diseases. Placement of a cage in the intervertebral space ...has become a routine clinical treatment for spinal fusion surgery to provide sufficient biomechanical stability, which is required to achieve bony ingrowth of the implant. Routinely used cages for clinical application are made of titanium (Ti) or polyetheretherketone (PEEK). Ti has been used since the 1980s; however, its shortcomings, such as impaired radiographical opacity and higher elastic modulus compared to bone, have led to the development of PEEK cages, which are associated with reduced stress shielding as well as no radiographical artefacts. Since PEEK is bioinert, its osteointegration capacity is limited, which in turn enhances fibrotic tissue formation and peri-implant infections. To address shortcomings of both of these biomaterials, interdisciplinary teams have developed biodegradable cages. Rooted in promising preclinical large animal studies, a hollow cylindrical cage (Hydrosorb™) made of 70:30 poly-l-lactide-co-d, l-lactide acid (PLDLLA) was clinically studied. However, reduced bony integration and unfavourable long-term clinical outcomes prohibited its routine clinical application. More recently, scaffold-guided bone regeneration (SGBR) with application of highly porous biodegradable constructs is emerging. Advancements in additive manufacturing technology now allow the cage designs that match requirements, such as stiffness of surrounding tissues, while providing long-term biomechanical stability. A favourable clinical outcome has been observed in the treatment of various bone defects, particularly for 3D-printed composite scaffolds made of medical-grade polycaprolactone (mPCL) in combination with a ceramic filler material. Therefore, advanced cage design made of mPCL and ceramic may also carry initial high spinal forces up to the time of bony fusion and subsequently resorb without clinical side effects. Furthermore, surface modification of implants is an effective approach to simultaneously reduce microbial infection and improve tissue integration. We present a design concept for a scaffold surface which result in osteoconductive and antimicrobial properties that have the potential to achieve higher rates of fusion and less clinical complications. In this review, we explore the preclinical and clinical studies which used bioresorbable cages. Furthermore, we critically discuss the need for a cutting-edge research program that includes comprehensive preclinical in vitro and in vivo studies to enable successful translation from bench to bedside. We develop such a conceptual framework by examining the state-of-the-art literature and posing the questions that will guide this field in the coming years.
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Direct Writing By Way of Melt Electrospinning Brown, Toby D.; Dalton, Paul D.; Hutmacher, Dietmar W.
Advanced materials (Weinheim),
December 15, 2011, Letnik:
23, Številka:
47
Journal Article
Recenzirano
Melt electrospun fibers of poly(ϵ‐caprolactone) are accurately deposited using an automated stage as the collector. Matching the translation speed of the collector to the speed of the melt ...electrospinning jet establishes control over the location of fiber deposition. In this sense, melt electrospinning writing can be seen to bridge the gap between solution electrospinning and direct writing additive manufacturing processes.
There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water ...content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0-2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising candidates for cartilage tissue-engineering applications.
There is a specialized niche for the electrohydrodynamic jetting of melts, from biomedical products to filtration and soft matter applications. The next frontier includes optics, microfluidics, ...flexible electronic devices, and soft network composites in biomaterial science and soft robotics. The recent emphasis on reproducibly direct‐writing continual molten jets has enabled a spectrum of contemporary microscale 3D objects to be fabricated. One strong suit of melt processing is the capacity for the jet to solidify rapidly into a fiber, thus fixing a particular structure into position. The ability to direct‐write complex and multiscaled architectures and structures has greatly contributed to a large number of recent studies, explicitly, toward fiber–hydrogel composites and fugitive inks, and has expanded into several biomedical applications such as cartilage, skin, periosteum, and cardiovascular tissue engineering. Following the footsteps of a publication that summarized melt electrowriting literature up to 2015, the most recent literature from then until now is reviewed to provide a continuous and comprehensive timeline that demonstrates the latest advances as well as new perspectives for this emerging technology.
The developments in melt electrospinning and melt electrowriting over the past 4 years are comprehensively reviewed to provide insight into this burgeoning field. The improvements in electrified jet control bring the technology to a stage where discrete structures can be designed to impart unique properties on such 3D‐printed products.
With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering – the ...combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue – is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three‐dimensional tissue‐like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell‐laden hydrogels are commonly used in biofabrication and are termed “bioinks”. Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three‐dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically‐relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico‐chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a “printable” hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.
Hydrogels are attractive cell carriers for regenerative medicine as they recapitulate several features of the natural extracellular matrix. However, biofabrication of three‐dimensional complex, tissue‐like structures with high shape fidelity dictates narrow boundaries for the physical properties of the hydrogels applied. This review focuses on strategies and new developments that address these physicochemical challenges.
Progress in advancing a system-level understanding of the complexity of human tissue development and regeneration is hampered by a lack of biological model systems that recapitulate key aspects of ...these processes in a physiological context. Hence, growing demand by cell biologists for organ-specific extracellular mimics has led to the development of a plethora of 3D cell culture assays based on natural and synthetic matrices. We developed a physiological microenvironment of semisynthetic origin, called gelatin methacryloyl (GelMA)-based hydrogels, which combine the biocompatibility of natural matrices with the reproducibility, stability and modularity of synthetic biomaterials. We describe here a step-by-step protocol for the preparation of the GelMA polymer, which takes 1-2 weeks to complete, and which can be used to prepare hydrogel-based 3D cell culture models for cancer and stem cell research, as well as for tissue engineering applications. We also describe quality control and validation procedures, including how to assess the degree of GelMA functionalization and mechanical properties, to ensure reproducibility in experimental and animal studies.
Biofilm research has grown exponentially over the last decades, arguably due to their contribution to hospital acquired infections when they form on foreign body surfaces such as catheters and ...implants. Yet, translation of the knowledge acquired in the laboratory to the clinic has been slow and/or often it is not attempted by research teams to walk the talk of what is defined as ‘bench to bedside’. We therefore reviewed the biofilm literature to better understand this gap. Our search revealed substantial development with respect to adapting surfaces and media used in models to mimic the clinical settings, however many of the in vitro models were too simplistic, often discounting the composition and properties of the host microenvironment and overlooking the biofilm-implant-host interactions. Failure to capture the physiological growth conditions of biofilms in vivo results in major differences between lab-grown- and clinically-relevant biofilms, particularly with respect to phenotypic profiles, virulence, and antimicrobial resistance, and they essentially impede bench-to-bedside translatability. In this review, we describe the complexity of the biological processes at the biofilm-implant-host interfaces, discuss the prerequisite for the development and characterization of biofilm models that better mimic the clinical scenario, and propose an interdisciplinary outlook of how to bioengineer biofilms in vitro by converging tissue engineering concepts and tools.
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