-
Science China. Life Sciences Aug 2023Synthetic biology provides a new paradigm for life science research ("build to learn") and opens the future journey of biotechnology ("build to use"). Here, we discuss... (Review)
Review
Synthetic biology provides a new paradigm for life science research ("build to learn") and opens the future journey of biotechnology ("build to use"). Here, we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology, including synthesis and assembly of a genome, DNA storage, gene editing, molecular evolution and de novo design of function proteins, cell and gene circuit engineering, cell-free synthetic biology, artificial intelligence (AI)-aided synthetic biology, as well as biofoundries. We also introduce the concept of quantitative synthetic biology, which is guiding synthetic biology towards increased accuracy and predictability or the real rational design. We conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.
Topics: Synthetic Biology; Artificial Intelligence; Biotechnology; Gene Editing; Genome
PubMed: 36753021
DOI: 10.1007/s11427-022-2214-2 -
Journal of Hepatology Jun 2023With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic... (Review)
Review
With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion - one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
Topics: Animals; Liver Transplantation; Organ Preservation; Liver; Perfusion; Bioengineering
PubMed: 37208105
DOI: 10.1016/j.jhep.2023.02.009 -
Nature Communications Oct 2023Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we...
Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.
Topics: Humans; Animals; Rabbits; Hydrogels; Cartilage; Collagen; Wound Healing; Cells, Cultured; Chondrogenesis; Tissue Engineering; Tissue Scaffolds; Cartilage, Articular
PubMed: 37802985
DOI: 10.1038/s41467-023-41594-y -
Plant Biotechnology Journal Aug 2023The fungal bioluminescence pathway (FBP) was identified from glowing fungi, which releases self-sustained visible green luminescence. However, weak bioluminescence...
The fungal bioluminescence pathway (FBP) was identified from glowing fungi, which releases self-sustained visible green luminescence. However, weak bioluminescence limits the potential application of the bioluminescence system. Here, we screened and characterized a C3'H1 (4-coumaroyl shikimate/quinate 3'-hydroxylase) gene from Brassica napus, which efficiently converts p-coumaroyl shikimate to caffeic acid and hispidin. Simultaneous expression of BnC3'H1 and NPGA (null-pigment mutant in A. nidulans) produces more caffeic acid and hispidin as the natural precursor of luciferin and significantly intensifies the original fungal bioluminescence pathway (oFBP). Thus, we successfully created enhanced FBP (eFBP) plants emitting 3 × 10 photons/min/cm , sufficient to illuminate its surroundings and visualize words clearly in the dark. The glowing plants provide sustainable and bio-renewable illumination for the naked eyes, and manifest distinct responses to diverse environmental conditions via caffeic acid biosynthesis pathway. Importantly, we revealed that the biosynthesis of caffeic acid and hispidin in eFBP plants derived from the sugar pathway, and the inhibitors of the energy production system significantly reduced the luminescence signal rapidly from eFBP plants, suggesting that the FBP system coupled with the luciferin metabolic flux functions in an energy-driven way. These findings lay the groundwork for genetically creating stronger eFBP plants and developing more powerful biological tools with the FBP system.
Topics: Metabolic Engineering; Plants; Luciferins
PubMed: 37155328
DOI: 10.1111/pbi.14068 -
Marine Drugs Jul 2023The marine-derived hyaluronic acid and other natural biopolymers offer exciting possibilities in the field of biomaterials, providing sustainable and biocompatible... (Review)
Review
The marine-derived hyaluronic acid and other natural biopolymers offer exciting possibilities in the field of biomaterials, providing sustainable and biocompatible alternatives to synthetic materials. Their unique properties and abundance in marine sources make them valuable resources for various biomedical and industrial applications. Due to high biocompatible features and participation in biological processes related to tissue healing, hyaluronic acid has become widely used in tissue engineering applications, especially in the wound healing process. The present review enlightens marine hyaluronan biomaterial providing its sources, extraction process, structures, chemical modifications, biological properties, and biocidal applications, especially for wound healing/dressing purposes. Meanwhile, we point out the future development of wound healing/dressing based on hyaluronan and its composites and potential challenges.
Topics: Hyaluronic Acid; Bandages; Biocompatible Materials; Tissue Engineering; Wound Healing
PubMed: 37623707
DOI: 10.3390/md21080426 -
Cell Nov 2023Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the...
Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the ∼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs.
Topics: Gene Expression Profiling; Genome, Fungal; Proteomics; Saccharomyces cerevisiae; Synthetic Biology; RNA, Transfer; Chromosomes, Artificial, Yeast
PubMed: 37944512
DOI: 10.1016/j.cell.2023.10.015 -
SLAS Technology Jun 2023
Topics: Bioprinting; Biocompatible Materials; Tissue Engineering
PubMed: 37257562
DOI: 10.1016/j.slast.2023.05.003 -
Nature Communications Feb 2024The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids,...
The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.
Topics: Microfluidics; Organoids; Tissue Engineering; Endothelium; Islets of Langerhans
PubMed: 38365780
DOI: 10.1038/s41467-024-45710-4 -
ACS Biomaterials Science & Engineering Jun 2023Bioprinting as an extension of 3D printing offers capabilities for printing tissues and organs for application in biomedical engineering. Conducting bioprinting in... (Review)
Review
Bioprinting as an extension of 3D printing offers capabilities for printing tissues and organs for application in biomedical engineering. Conducting bioprinting in space, where the gravity is zero, can enable new frontiers in tissue engineering. Fabrication of soft tissues, which usually collapse under their own weight, can be accelerated in microgravity conditions as the external forces are eliminated. Furthermore, human colonization in space can be supported by providing critical needs of life and ecosystems by 3D bioprinting without relying on cargos from Earth, e.g., by development and long-term employment of living engineered filters (such as sea sponges-known as critical for initiating and maintaining an ecosystem). This review covers bioprinting methods in microgravity along with providing an analysis on the process of shipping bioprinters to space and presenting a perspective on the prospects of zero-gravity bioprinting.
Topics: Humans; Regenerative Medicine; Ecosystem; Bioprinting; Weightlessness; Tissue Engineering; Printing, Three-Dimensional
PubMed: 37155968
DOI: 10.1021/acsbiomaterials.3c00195 -
Molecular Plant Dec 2023The diterpenoid paclitaxel (Taxol) is a chemotherapy medication widely used as a first-line treatment against several types of solid cancers. The supply of paclitaxel...
The diterpenoid paclitaxel (Taxol) is a chemotherapy medication widely used as a first-line treatment against several types of solid cancers. The supply of paclitaxel from natural sources is limited. However, missing knowledge about the genes involved in several specific metabolic steps of paclitaxel biosynthesis has rendered it difficult to engineer the full pathway. In this study, we used a combination of transcriptomics, cell biology, metabolomics, and pathway reconstitution to identify the complete gene set required for the heterologous production of paclitaxel. We identified the missing steps from the current model of paclitaxel biosynthesis and confirmed the activity of most of the missing enzymes via heterologous expression in Nicotiana benthamiana. Notably, we identified a new C4β-C20 epoxidase that could overcome the first bottleneck of metabolic engineering. We used both previously characterized and newly identified oxomutases/epoxidases, taxane 1β-hydroxylase, taxane 9α-hydroxylase, taxane 9α-dioxygenase, and phenylalanine-CoA ligase, to successfully biosynthesize the key intermediate baccatin III and to convert baccatin III into paclitaxel in N. benthamiana. In combination, these approaches establish a metabolic route to taxoid biosynthesis and provide insights into the unique chemistry that plants use to generate complex bioactive metabolites.
Topics: Synthetic Biology; Taxoids; Paclitaxel; Mixed Function Oxygenases
PubMed: 37897038
DOI: 10.1016/j.molp.2023.10.016