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CRISPR FokI Dead Cas9 System: Principles and Applications in Genome Engineering.
Saifaldeen, M, Al-Ansari, DE, Ramotar, D, Aouida, M
Cells. 2020;(11)
Abstract
The identification of the robust clustered regularly interspersed short palindromic repeats (CRISPR) associated endonuclease (Cas9) system gene-editing tool has opened up a wide range of potential therapeutic applications that were restricted by more complex tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Nevertheless, the high frequency of CRISPR system off-target activity still limits its applications, and, thus, advanced strategies for highly specific CRISPR/Cas9-mediated genome editing are continuously under development including CRISPR-FokI dead Cas9 (fdCas9). fdCas9 system is derived from linking a FokI endonuclease catalytic domain to an inactive Cas9 protein and requires a pair of guide sgRNAs that bind to the sense and antisense strands of the DNA in a protospacer adjacent motif (PAM)-out orientation, with a defined spacer sequence range around the target site. The dimerization of FokI domains generates DNA double-strand breaks, which activates the DNA repair machinery and results in genomic edit. So far, all the engineered fdCas9 variants have shown promising gene-editing activities in human cells when compared to other platforms. Herein, we review the advantages of all published variants of fdCas9 and their current applications in genome engineering.
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Understanding and leveraging cell metabolism to enhance mesenchymal stem cell transplantation survival in tissue engineering and regenerative medicine applications.
Salazar-Noratto, GE, Luo, G, Denoeud, C, Padrona, M, Moya, A, Bensidhoum, M, Bizios, R, Potier, E, Logeart-Avramoglou, D, Petite, H
Stem cells (Dayton, Ohio). 2020;(1):22-33
Abstract
In tissue engineering and regenerative medicine, stem cell-specifically, mesenchymal stromal/stem cells (MSCs)-therapies have fallen short of their initial promise and hype. The observed marginal, to no benefit, success in several applications has been attributed primarily to poor cell survival and engraftment at transplantation sites. MSCs have a metabolism that is flexible enough to enable them to fulfill their various cellular functions and remarkably sensitive to different cellular and environmental cues. At the transplantation sites, MSCs experience hostile environments devoid or, at the very least, severely depleted of oxygen and nutrients. The impact of this particular setting on MSC metabolism ultimately affects their survival and function. In order to develop the next generation of cell-delivery materials and methods, scientists must have a better understanding of the metabolic switches MSCs experience upon transplantation. By designing treatment strategies with cell metabolism in mind, scientists may improve survival and the overall therapeutic potential of MSCs. Here, we provide a comprehensive review of plausible metabolic switches in response to implantation and of the various strategies currently used to leverage MSC metabolism to improve stem cell-based therapeutics.
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Herbal Remedies as Potential in Cartilage Tissue Engineering: An Overview of New Therapeutic Approaches and Strategies.
Buhrmann, C, Honarvar, A, Setayeshmehr, M, Karbasi, S, Shakibaei, M, Valiani, A
Molecules (Basel, Switzerland). 2020;(13)
Abstract
It is estimated that by 2023, approximately 20% of the population of Western Europe and North America will suffer from a degenerative joint disease commonly known as osteoarthritis (OA). During the development of OA, pro-inflammatory cytokines are one of the major causes that drive the production of inflammatory mediators and thus of matrix-degrading enzymes. OA is a challenging disease for doctors due to the limitation of the joint cartilage's capacity to repair itself. Though new treatment approaches, in particular with mesenchymal stem cells (MSCs) that integrate the tissue engineering (TE) of cartilage tissue, are promising, they are not only expensive but more often do not lead to the regeneration of joint cartilage. Therefore, there is an increasing need for novel, safe, and more effective alternatives to promote cartilage joint regeneration and TE. Indeed, naturally occurring phytochemical compounds (herbal remedies) have a great anti-inflammatory, anti-oxidant, and anabolic potential, and they have received much attention for the development of new therapeutic strategies for the treatment of inflammatory diseases, including the prevention of age-related OA and cartilage TE. This paper summarizes recent research on herbal remedies and their chondroinductive and chondroprotective effects on cartilage and progenitor cells, and it also emphasizes the possibilities that exist in this research area, especially with regard to the nutritional support of cartilage regeneration and TE, which may not benefit from non-steroidal anti-inflammatory drugs (NSAIDs).
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4.
Natural Medicinal Compounds in Bone Tissue Engineering.
Bose, S, Sarkar, N
Trends in biotechnology. 2020;(4):404-417
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Abstract
Recent advances in 3D printing have provided unprecedented opportunities in bone tissue engineering applications for producing a variety of complex patient-specific implants for the treatment of critical-sized bone defects. Natural medicinal compounds (NMCs) with osteogenic potential can be incorporated into these 3D-printed parts to improve bone formation and therefore enhance implant performance. Using NMCs to treat bone-related disorders may prove to be a healthy preventive choice as they are considered safe, have lesser or no side effects, and are more suitable for prolonged use than synthetic drugs. In this review paper, the current challenges of bone tissue engineering are addressed briefly, highlighting the immense potential of NMCs integrated within tissue engineering scaffolds for orthopedic and dental applications.
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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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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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7.
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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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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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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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.