Periodic Reporting for period 3 - SYNTISU (Remotely-controlled functional synthetic tissues)
Reporting period: 2022-08-01 to 2024-01-31
We are making synthetic tissues with potential applications in medicine. In the short-term, synthetic tissues will be used to deliver therapeutics. Delivery will be controlled in time and space, i.e. it might be confined to a particular part of the body or turned on-and-off at will. Ultimately, synthetic tissues will be used for sophisticated applications. For example, they will act as components of surgical implants to repair traumatic injuries or restore damaged organs. Synthetic tissues will be safe, because they do not contain a genome and therefore cannot grow like implants that contain living cells capable of replication. Our synthetic tissues are formed from patterned 3D-printed picoliter droplet networks. The droplets form compartments that mimic cells. Indeed, a picoliter is approximately the same volume as a human cell.
In time, we will form synthetic tissues that are functionally active and can be controlled by external inputs, such as light, heat or magnetism. Our recent work has produced significant progress towards this goal. First, we have made advances in the construction of synthetic tissues, which have included perfecting the way in which droplets pack during 3D printing and developing the ability to assemble centimeter-sized structures from printed millimeter building blocks. Second, synthetic tissues have also been built from water-containing gels. These structures have the extraordinary ability to change shape in response to heat and light, and might ultimately be able to navigate through the human body. Third, functional properties built into the synthetic tissues have included the ability to process several small-molecule inputs signals in parallel, which would allow a response only if say two inputs were present; these inputs could be symptomatic of disease. Further, the release of small molecules from synthetic tissues in a controlled manner has been demonstrated, heralding controlled drug release. The printing of living cells based on the technology for synthetic tissues has also been explored and is proving to be a major spin-off. For example, brain tissues, potentially for implantation, have been constructed in this manner and bacteria have been patterned at the sub-millimeter scale for studies of the microbiome.
At this early stage, we have published eleven papers detailing out endeavours in the scientific literature. Our work has not yet been exploited in the sphere of medicine, but we continue to progress towards this ambition.
In time, we will form synthetic tissues that are functionally active and can be controlled by external inputs, such as light, heat or magnetism. Our recent work has produced significant progress towards this goal. First, we have made advances in the construction of synthetic tissues, which have included perfecting the way in which droplets pack during 3D printing and developing the ability to assemble centimeter-sized structures from printed millimeter building blocks. Second, synthetic tissues have also been built from water-containing gels. These structures have the extraordinary ability to change shape in response to heat and light, and might ultimately be able to navigate through the human body. Third, functional properties built into the synthetic tissues have included the ability to process several small-molecule inputs signals in parallel, which would allow a response only if say two inputs were present; these inputs could be symptomatic of disease. Further, the release of small molecules from synthetic tissues in a controlled manner has been demonstrated, heralding controlled drug release. The printing of living cells based on the technology for synthetic tissues has also been explored and is proving to be a major spin-off. For example, brain tissues, potentially for implantation, have been constructed in this manner and bacteria have been patterned at the sub-millimeter scale for studies of the microbiome.
At this early stage, we have published eleven papers detailing out endeavours in the scientific literature. Our work has not yet been exploited in the sphere of medicine, but we continue to progress towards this ambition.
The work performed so far is summarized in the eleven Publications listed in this Scientific Report. Advances in the construction of synthetic tissues have included improvements in droplet packing, the assembly of enlarged structures from printed building blocks and the transfer of materials from the printing substrate (oil) to water. Synthetic tissues built from responsive hydrogels were also explored during the funding period. Functional properties introduced into the synthetic tissues have included the ability to process parallel input signals and the release of small molecules in a controlled. The printing of living cells based on the technology for synthetic tissues has also been explored and is proving to be a major spin-off from SYNTISU. For example, brain tissues have been constructed in this manner and bacteria have been patterned at the sub-millimetre scale for studies of the microbiome.
All of our research is original work and therefore goes beyond the state-of-the-art as outlined above and as described in detail in our publications. We are on course to fulfil the objectives of SYNTISU, which were described in the proposal and represent goals that exceed the state-of-the-art:
OBJECTIVE 1. Engineering optimized 3D-printed droplet networks: 3D-printed droplet networks will be perfected. Strong and stable synthetic tissues will be produced with complex patterning at high fidelity and high resolution. They will be transferred to and function in aqueous media. Larger structures (cm-scale) will be built by the hierarchical assembly of mm-scale networks.
OBJECTIVE 2. Building function into synthetic tissues: Synthetic tissues will be functionalized to: undergo reversible shape change; take up, transform and release small molecules; and generate and use energy.
OBJECTIVE 3. Remote control of synthetic tissues: Spatiotemporal control of synthetic tissues by light, temperature and magnetism will be demonstrated. Outputs will include protein expression, ATP generation and shape change. Additional aspects of control will include small-molecule interactions with riboswitches, simple computation with multiple input stimuli, and the internal transmission of signals. Remote control of synthetic tissues will be useful in many applications.
OBJECTIVE 4. Illustrative applications of synthetic tissues. The synthesis and release of peptide and protein therapeutics and the spatial control of living cells in culture will be demonstrated.
We have in several cases already gone beyond these objectives. For example, the printing of living cells based on the technology for synthetic tissues has been explored and is proving to be a major spin-off from SYNTISU.
OBJECTIVE 1. Engineering optimized 3D-printed droplet networks: 3D-printed droplet networks will be perfected. Strong and stable synthetic tissues will be produced with complex patterning at high fidelity and high resolution. They will be transferred to and function in aqueous media. Larger structures (cm-scale) will be built by the hierarchical assembly of mm-scale networks.
OBJECTIVE 2. Building function into synthetic tissues: Synthetic tissues will be functionalized to: undergo reversible shape change; take up, transform and release small molecules; and generate and use energy.
OBJECTIVE 3. Remote control of synthetic tissues: Spatiotemporal control of synthetic tissues by light, temperature and magnetism will be demonstrated. Outputs will include protein expression, ATP generation and shape change. Additional aspects of control will include small-molecule interactions with riboswitches, simple computation with multiple input stimuli, and the internal transmission of signals. Remote control of synthetic tissues will be useful in many applications.
OBJECTIVE 4. Illustrative applications of synthetic tissues. The synthesis and release of peptide and protein therapeutics and the spatial control of living cells in culture will be demonstrated.
We have in several cases already gone beyond these objectives. For example, the printing of living cells based on the technology for synthetic tissues has been explored and is proving to be a major spin-off from SYNTISU.