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1.
Revisiting the insights and applications of protein engineered hydrogels.
J, B, Chanda, K, M M, B
Materials science & engineering. C, Materials for biological applications. 2019;:312-327
Abstract
Utilization of protein-protein interactions or protein-peptide interactions has led to new crosslinking chemistries, resulting into protein hydrogels. Enzyme catalyzed crosslinking of specific amino acids has also been used to generate crosslinked protein hydrogels. Weak, temporary, reversible or non-covalently crosslinked protein gels as well as strong, permanent, irreversible or covalently crosslinked protein gels with mechanical strengths of varying degrees are generated by means of various crosslinking strategies. These protein hydrogels are tailored by means of protein engineering and recombinant DNA technology, depending on its end use as scaffolds for specific tissue engineering, drug delivery, wound dressings etc. This review aims to cover the advancements in the use of protein engineering along with different crosslinking techniques to create novel protein hydrogels that finds various applications in biomedical industries.
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2.
Dynamic in vitro models for tumor tissue engineering.
Karami, D, Richbourg, N, Sikavitsas, V
Cancer letters. 2019;:178-185
Abstract
Cancer research uses in vitro studies for controllable analysis of tumor behavior and preclinical testing of therapeutics. Shortcomings of basic cell culture systems in recreating in vivo interactions have driven the development of more efficient and biomimetic in vitro environments for cancer research. Assimilation of certain developments in tissue engineering will accelerate and improve the design of these environments. With the continual improvement of the tumor engineering field, the next step is towards macroscopic systems such as scaffold-supported, flow-perfused macroscale tumor bioreactors. Surface modifications of synthetic scaffolds allow for targeted cell adhesion and improved ECM development. Flow perfusion has emerged as means to expose cancerous tissues to critical biomechanical forces for tumor progression while simultaneously improving nutrient and waste transport. Macroscale perfusable systems allow for non-destructive real-time monitoring using biosensors capable of improving understanding of in vitro tumor development at reduced cost and waste. The combination of macroscale perfusable systems, surface-modified synthetic scaffolds, and non-destructive real-time monitoring will provide advanced platforms for in vitro modeling of tumor development, with broad applications in basic tumor research and preclinical drug development.
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3.
Enamel biomimetics-fiction or future of dentistry.
Pandya, M, Diekwisch, TGH
International journal of oral science. 2019;(1):8
Abstract
Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods. In recent years, multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility. In the present review, we discuss five pathways toward enamel tissue engineering, (i) enamel synthesis using physico-chemical means, (ii) protein matrix-guided enamel crystal growth, (iii) enamel surface remineralization, (iv) cell-based enamel engineering, and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis. So far, physical synthesis approaches using extreme environmental conditions such as pH, heat and pressure have resulted in the formation of enamel-like crystal assemblies. Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals. To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix. Other studies reviewed here have employed amelogenin-derived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces. So far, cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines. Going forward, these limitations may be overcome by new cell culture technologies. Finally, whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration. In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.
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4.
Bioprinting Approaches to Engineering Vascularized 3D Cardiac Tissues.
Puluca, N, Lee, S, Doppler, S, Münsterer, A, Dreßen, M, Krane, M, Wu, SM
Current cardiology reports. 2019;(9):90
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Abstract
PURPOSE OF REVIEW 3D bioprinting technologies hold significant promise for the generation of engineered cardiac tissue and translational applications in medicine. To generate a clinically relevant sized tissue, the provisioning of a perfusable vascular network that provides nutrients to cells in the tissue is a major challenge. This review summarizes the recent vascularization strategies for engineering 3D cardiac tissues. RECENT FINDINGS Considerable steps towards the generation of macroscopic sizes for engineered cardiac tissue with efficient vascular networks have been made within the past few years. Achieving a compact tissue with enough cardiomyocytes to provide functionality remains a challenging task. Achieving perfusion in engineered constructs with media that contain oxygen and nutrients at a clinically relevant tissue sizes remains the next frontier in tissue engineering. The provisioning of a functional vasculature is necessary for maintaining a high cell viability and functionality in engineered cardiac tissues. Several recent studies have shown the ability to generate tissues up to a centimeter scale with a perfusable vascular network. Future challenges include improving cell density and tissue size. This requires the close collaboration of a multidisciplinary teams of investigators to overcome complex challenges in order to achieve success.
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5.
Fabrication of biocomposite scaffolds made with modified hydroxyapatite inclusion of chitosan-grafted-poly(methyl methacrylate) for bone tissue engineering.
Tithito, T, Suntornsaratoon, P, Charoenphandhu, N, Thongbunchoo, J, Krishnamra, N, Tang, IM, Pon-On, W
Biomedical materials (Bristol, England). 2019;(2):025013
Abstract
In the present study, composite scaffolds of chitosan-graft-poly(methyl methacrylate) (Chi-g-PMMA) and mineral ions-loaded hydroxyapatite (mHA) (obtained by the hydrothermal treatment of hydroxyapatite (HA) in a simulated body fluid (SBF) solution (mHA@Chi-g-PMMA)) were prepared by the blending method. The physical properties, bioactivity, biological properties and their capabilities for sustained drug and protein release were studied. Physicochemical analysis showed a successful incorporation of the mineral ions in the HA particles and a good distribution of the mHA within the Chi-g-PMMA polymer matrix. The compressive strength and the Young's modulus were 15.760 ± 0.718 and 658.452 ± 17.020 MPa, respectively. In bioactivity studies, more apatite formation on the surface were seen after immersion in the SBF solution. In vitro growth experiments using UMR-106 osteoblast-like cells on the mHA@Chi-g-PMMA scaffold case showed that the attachment, viability and proliferation of the cells on the scaffolds had improved after 7 d of immersion. The in vitro release of two compounds (the cancer drug, doxorubicin (DOX)) and bovine serum albumin (BSA)), which had been attached to separate mHA@Chi-g-PMMA scaffolds, were studied to determine their suitability as drug delivery vehicles. It was found that the sustained release of DOX was 73.95% and of BSA was 57.27% after 25 h of incubation. These experimental results demonstrated that the mHA@Chi-g-PMMA composite can be utilized as a scaffold for bone cells ingrowth and also be used for drug delivery during the bone repairing.
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6.
A Growth Factor-Free Co-Culture System of Osteoblasts and Peripheral Blood Mononuclear Cells for the Evaluation of the Osteogenesis Potential of Melt-Electrowritten Polycaprolactone Scaffolds.
Hammerl, A, Diaz Cano, CE, De-Juan-Pardo, EM, van Griensven, M, Poh, PSP
International journal of molecular sciences. 2019;(5)
Abstract
Scaffolds made of biodegradable biomaterials are widely used to guide bone regeneration. Commonly, in vitro assessment of scaffolds' osteogenesis potential has been performed predominantly in monoculture settings. Hence, this study evaluated the potential of an unstimulated, growth factor-free co-culture system comprised of osteoblasts (OB) and peripheral blood mononuclear cells (PBMC) over monoculture of OB as an in vitro platform for screening of bone regeneration potential of scaffolds. Particularly, this study focuses on the osteogenic differentiation and mineralized matrix formation aspects of cells. The study was performed using scaffolds fabricated by means of a melt electrowriting (MEW) technique made of medical-grade polycaprolactone (PCL), with or without a surface coating of calcium phosphate (CaP). Qualitative results, i.e., cell morphology by fluorescence imaging and matrix mineralization by von Kossa staining, indicated the differences in cell behaviours in response to scaffolds' biomaterial. However, no obvious differences were noted between OB and OB+PBMC groups. Hence, quantitative investigation, i.e., alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activities, and gene expression were quantitatively evaluated by reverse transcription-polymerase chain reaction (RT-qPCR), were evaluated only of PCL/CaP scaffolds cultured with OB+PBMC, while PCL/CaP scaffolds cultured with OB or PBMC acted as a control. Although this study showed no differences in terms of osteogenic differentiation and ECM mineralization, preliminary qualitative results indicate an obvious difference in the cell/non-mineralized ECM density between scaffolds cultured with OB or OB+PBMC that could be worth further investigation. Collectively, the unstimulated, growth factor-free co-culture (OB+PBMC) system presented in this study could be beneficial for the pre-screening of scaffolds' in vitro bone regeneration potential prior to validation in vivo.
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7.
X-ray physics-based CT-to-composition conversion applied to a tissue engineering scaffold, enabling multiscale simulation of its elastic behavior.
Szlazak, K, Vass, V, Hasslinger, P, Jaroszewicz, J, Dejaco, A, Idaszek, J, Scheiner, S, Hellmich, C, Swieszkowski, W
Materials science & engineering. C, Materials for biological applications. 2019;:389-396
Abstract
Nowadays, the assessment of the mechanical competence of tissue engineering scaffolds based on computer simulations is a well-accepted technology. Typically, such simulations are performed by means of the Finite Element (FE) method, with the underlying structural model being created based on micro-computed tomography (microCT). Here, this analysis modality is applied to a new, ternary composite, consisting of PHBV, i.e. poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PLGA, i.e. poly(lactic-co-glycolide), as well as of TCP, i.e. tricalcium phosphate hydrate. The studied scaffold structure is made up by fibers of this new composite material, manufactured by means of the rapid prototyping method. The data collected from microCT is utilized for adequately defining the mechanical properties of the FE model. In particular, the three-dimensional field of grey values is interpreted in terms of the underlying field of attenuation coefficients, taking into account the photon energy employed in microCT imaging, eventually allowing for calculation of the three-dimensionally distributed, voxel-specific composition of the studied material. For the sake of keeping the FE simulations as efficient as possible, groups of voxels are combined into one finite element; the grey value of the latter is obtained by volume averaging. Employing a two-step micromechanical homogenization scheme, the experimentally accessible stiffness of the three constituents (PHBV, PLGA, and TCP) is then, finite element by finite element, upscaled to the composition-dependent stiffness of the composite material. The plausibility and adequacy of the FE model is demonstrated by simulating the effects of uniaxial compression on the scaffold structure, in terms of resulting stress and strain fields, highlighting the importance of the fiber junctions (as they are the mechanically most stressed regions), and that neglecting the material heterogeneity would lead to a potentially significant underestimation of stresses and strains. Finally, a comparison is made of the employed analysis modality of microCT data with a previously pursued, simplified analysis strategy, highlighting the conceptual superiority of the former, and pointing out the application limits of the latter.
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8.
Generating an Artificial Intestine for the Treatment of Short Bowel Syndrome.
Kovler, ML, Hackam, DJ
Gastroenterology clinics of North America. 2019;(4):585-605
Abstract
Intestinal failure is defined as the inability to maintain fluid, nutrition, energy, and micronutrient balance that leads to the inability to gain or maintain weight, resulting in malnutrition and dehydration. Causes of intestinal failure include short bowel syndrome (ie, the physical loss of intestinal surface area and severe intestinal dysmotility). For patients with intestinal failure who fail to achieve enteral autonomy through intestinal rehabilitation programs, the current treatment options are expensive and associated with severe complications. Therefore, the need persists for next-generation therapies, including cell-based therapy, to increase intestinal regeneration, and development of the tissue-engineered small intestine.
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9.
Integrated additive design and manufacturing approach for the bioengineering of bone scaffolds for favorable mechanical and biological properties.
Valainis, D, Dondl, P, Foehr, P, Burgkart, R, Kalkhof, S, Duda, GN, van Griensven, M, Poh, PSP
Biomedical materials (Bristol, England). 2019;(6):065002
Abstract
Additive manufacturing (AM) presents the possibility of personalized bone scaffolds with unprecedented structural and functional designs. In contrast to earlier conventional design concepts, e.g. raster-angle, a workflow was established to produce scaffolds with triply periodic minimal surface (TPMS) architecture. A core challenge is the realization of such structures using melt-extrusion based 3D printing. This study presents methods for generation of scaffold design files, finite element (FE) analysis of scaffold Young's moduli, AM of scaffolds with polycaprolactone (PCL), and a customized in vitro assay to evaluate cell migration. The reliability of FE analysis when using computer-aided designed models as input may be impeded by anomalies introduced during 3D printing. Using micro-computed tomography reconstructions of printed scaffolds as an input for numerical simulation in comparison to experimentally obtained scaffold Young's moduli showed a moderate trend (R 2 = 0.62). Interestingly, in a preliminary cell migration assay, adipose-derived mesenchymal stromal cells (AdMSC) migrated furthest on PCL scaffolds with Diamond, followed by Gyroid and Schwarz P architectures. A similar trend, but with an accelerated AdMSC migration rate, was observed for PCL scaffolds surface coated with calcium-phosphate-based apatite. We elaborate on the importance of start-to-finish integration of all steps of AM, i.e. design, engineering and manufacturing. Using such a workflow, specific biological and mechanical functionality, e.g. improved regeneration via enhanced cell migration and higher structural integrity, may be realized for scaffolds intended as temporary guiding structures for endogenous tissue regeneration.
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10.
The applications of regenerative medicine in sinus lift procedures: A systematic review.
Correia, F, Pozza, DH, Gouveia, S, Felino, A, Faria E Almeida, R
Clinical implant dentistry and related research. 2018;(2):229-242
Abstract
BACKGROUND Findings in regenerative medicine applied to the sinus lift procedures. PURPOSE Evaluate the effectiveness of regenerative medicine in sinus lift. MATERIALS AND METHODS An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. RESULTS Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. CONCLUSION Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results.