One liner: Theranautilus are developing dental stem cells with internalised magnetic bioglass nanobots for remote-controlled targeted bone growth, to tackle: bone loss, fracture and root canal failure.
Longevity Dealflow WG team
Shepherd: Rhys Anderson
Other squad members: Tovah Wolf
Simple Summary
Bone loss and tooth fracture are common in geriatric patients (osteoporosis/osteopenia affect around 18% of the global population), which if untreated can lead to other complications. Theranautilus are a lab spinoff working to commercialize biohybrid stem cells with internalized magnetic nanobots, to allow for remote control of the stem cells inside a living body to direct them to a target location. Coating the nanobots with calcium silicate bioglass induces an osteogenic phenotype in the stem cells, allowing for targeted bone formation.
The final product will be cryopreserved biohybrid stem cells to enable easy shipment and easy storage at the hospital level along with the control device to manoeuver them.
The biohybrid nanobot technology can also be applied to root canal failure, which is extremely common due to bacterial infections being inaccessible to treatment and also traumatic injuries where a fracture or crack occurs during the root canal procedure leading to infection. The nanobots can be remotely guided through dentine tubules to penetrate deep into the dentine to the site of bacterial infection where magnetic fields can be applied to induce hyperthermia death.
Whilst maintaining dental health is important for healthy ageing, the long term plan is that their innovative technology for targeted delivery of stem cells could be used as a regenerative therapy for many age-related conditions, such as skeletal bone regeneration for osteoporosis/osteopenia, hearing loss and neural regeneration in stroke patients etc. However, teeth are ideal for testing this new cell-based therapy for several reasons including the availability/accessibility of stem cells in the dental pulp.
Problem
Treatment options for dental bone loss and fracture are inefficient and have high failure rates, excessive treatment times, and excessive schedule delays.
Root canal treatment failure is very common, occuring in around 10% of cases (up to 5 million per year in the US alone). The main cause of endodontic failure is the persistence of microorganisms that cause an intraradicular or extraradicular infection and become resistant to disinfection measures.
Opportunity
The Theranautilus team has been working on nanorobotics for over a decade. Their recent publication using nanorobots to prevent root-canal treatment failure has been very well-received by the dental science community.
Stem cells are already used in many therapeutic applications and hold immense potential in regenerative medicine. The team are building stem cells that can be magnetically manoeuvred to the target site due to the presence of magnetic nanostructures inside the cells. These nanostructures (called CALBOTs) are coated with calcium silicate bioglass to induce an osteogenic phenotype and trigger bone growth.
Theranautilus are seeking funding to translate their proof-of-concept by generating data over a larger sample and undergoing good laboratory practice (GLP) documentation for biohybrid stem cell production.
They have successfully developed the first working prototype: THERADRIVE - which has a miniature coil suitable for use in an adult human jaw. This coil system is a unique medical device that can generate up to 60 Gauss rotating fields in any direction to drive stem cells inside the teeth.
Theradrive prototype
Cell toxicity tests:
The team have cell toxicity data and know the exact concentration to make the dental stem cells bioactive to trigger bone growth whilst simultaneously keeping them viable for over a month. This has been confirmed by the team on mouse preosteoblasts (MC3T3 E1 subclone 4 mouse calvarial pre-osteoblasts (ATCC, USA) ).
Bone growth tests:
After establishing cell cytotoxicity and confirming the magnetic bioglass is not cytotoxic, they established the bone growth potential of their nanomaterials.
Representative images of bone growth localized to the regions where CALBOTS are present
Workflow
Dental Pulp Stem Cells (DPSCs) will be extracted from wisdom teeth and chilled in HBSS for up to 12 hours. The laboratory will perform quality control on the DPSCs followed by cryopreservation. When required for therapy, the cells will be thawed and expanded, incubated with CALBOTs, before returning to the patient.
Theranautilus workflow
N.B for root canal failure, the nanobots alone can be guided down the dentinal tubules, followed by application of rapidly varying magnetic fields to heat the nanobots and cause hyperthermia-induced death in bacteria.
Root canal failure update: the team have further optimised the procedure for root canal in a rat, including miniaturisation of root canal instruments to custom fit the rat’s oral cavity. They have performed successful root canal procedures on the rats and have developed a protocol which will be followed for the upcoming randomised controlled trials in association with a research hospital. *Data requested.
Estimated cost analysis of the treatments developed by Theranautilus for various ailments
| Current Treatment | Problem | Cost of treatment | Theranautilus’ treatment | Solution | Estimated Cost | |
|---|---|---|---|---|---|---|
| Fracture | Bioactive glass | Slow (Few months) | ~27000 USD * | Biohybrid stem cells | Targeted delivery of preconditioned stem cells. This reduces time to heal and overall hospital costs | ~18000 USD |
| Bone loss | Ionomer/ Bioactive glass grafts | Inefficient and high rate of failure | ~3000 USD ** | Biohybrid stem cells with magnetic graft | Targeted osteogenic stem cells with magnetic field to keep them in place | ~2500 – 3000 USD |
| Root canal failure | NIL | Traumatic dental injuries where a fracture or crack has occurred during the root canal procedure leading to infection | Failure leads to loss of tooth | Delivery of CALBOTs and Biohybrid stem cells*** | Deeper penetration of bioglass loaded CALBOTs and stem cells to the site of fracture to repair and prevent tooth loss | ~80 USD added to current root canal cost |
*Geurts J, van Vugt T, Thijssen E, Arts JJ. Cost-Effectiveness Study of One-Stage Treatment of Chronic Osteomyelitis with Bioactive Glass S53P4. Materials (Basel). 2019 Sep 30;12(19):3209. doi: 10.3390/ma12193209. PMID: 31574970; PMCID: PMC6804190.
** Zeitlin BD. Banking on teeth - Stem cells and the dental office. Biomed J. 2020 Apr;43(2):124-133. doi: 10.1016/j.bj.2020.02.003.
*** Mobile nanobots for prevention of root canal treatment failure. Dasgupta D, Peddi S, Saini DK, Ghosh A Advanced Healthcare Materials 2022 Apr 28 https://doi.org/10.1002/adhm.202200232
The above table shows the estimated cost a patient incurs for hospital stay, CT scan/ MRI etc (Figure 5). Theranaultilus’ technology can substantially reduce this by reducing hospital stay/visit by ~40%. Below is the core cost of the technology, focusing on engineering of the stem cells.
Current Cost of stem cell banking:
a) Initial Processing : $500 - $2000 (USD)
b) Annual Maintenance (Recurring): $99 - $264 (USD)
Breakdown of estimated cost for modifying stem cells:
a) Materials cost (consumables – One time cost per patient): $50 - $100 USD
b) Service Charge (Optional; In case Theranautilus provides lab support; cost per patient): $20 USD
Experimental plan and Budget
Pre-Clinical Studies 1a: Toxicity assays of magnetic bioglass on mesenchymal human stem cells (MSCs).
To perfect the protocol of incubating MSCs with magnetic bioglass and the optimum concentration of magnetic bioglass to be used. Cell viability assays at different day points – days 1, 4, and 7. Similar experimental data has been done on mouse pre-osteoblasts, and the same protocol will be followed with necessary adjustments.
Required Funding: $31,210
Duration: 3 Months
Pre-Clinical Studies 2a: Efficacy of magnetic bioglass in triggering bone growth in mesenchymal human stem cells.
To test if bone growth is happening with spatial control, by demonstrating the magnetic manoeuvrability of stem cells to target bone fracture and the possibility of patterned bone growth.
Required Funding: $71,465
Duration: 6 Months
Pre-Clinical Studies 1b: GLP certification for magnetic bioglass fabrication.
This is the next step before applying for clinical trials. The magnetic bioglass synthesized by Theranautilus’ protocol will undergo GLP certification before human trials, where the team plans to collaborate closely with a GLP certified lab to provide this certification.
Required Funding: $38,150
Duration: 6 Months
Pre-Clinical Studies 2b: Device design to deliver mesenchymal stem cells in the human teeth.
The device is protected by the patent application (US20220226073A1 - Controlling motion of magnetically-driven microscopic particles - Google Patents). The team will look at making minor modifications to their current control algorithm and machine to work with CBCT or x-ray data to drive magnetic maneuverable stem cells to the fracture site. An image processing component may be added to the device to make it more efficient.
Required Funding: $43,000
Duration: 6 Months
Total budget: $183,825
VitaDAO Funding Terms
$183,000 (USD) via a Sponsored Development Agreement in exchange for 15.25% of the Net Company Receipts (valued at US $1.2M based on an equity raise), encompassing the following indications for CALBOTs therapies: bone loss, tooth fracture and root canal failure.
IP Roadmap
Theranautilus owns the IP to manufacture the devices to control their nanostructures in human teeth. They filed the “composition of matter” patent in 2022 and we will go ahead with a PCT to protect it in the US/EU region. The patent protecting the method of creating biohybrid stem cells will be filed once the bone growth data and toxicity experiments are repeated.
Team
Dr. Debayan Dasgupta - Co-founder, Director
Expert in electronics and optical engineering. Built several unique devices to image and control nanorobots in cancer physiology during PhD.
Dr. Shanmukh Srinivas - Co-founder, Director
Endodontic surgeon with extensive clinical experience and medical knowledge.
Prof. Ambarish Ghosh - Co-founder, Director
Built several unique devices to image and control nanorobots in cancer physiology during PhD. Co-inventor of the technique used to fabricate helical nanorobots.
Mentors
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Prof. Navakant Bhat - Cofounder and CEO, Pathsodh
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Dr. Bruce Lieberthal, DDS Chief Innovation Officer, Henry Schein
Additional information
Recently awarded a BIRAC grant from the Government of India which is analogous to the Small Business Innovation Research (or SBIR) program in USA. It’s highly competitive and open doors for larger government grants in future.
Press:
Featured on Board of Innovation’s Top 10 med-tech companies solving real health challenges
Proof-of-concept publications from the Theranautilus team:
Mobile nanobots for prevention of root canal treatment failure.
Dasgupta D, Peddi S, Saini DK, Ghosh A Advanced Healthcare Materials 2022 Apr 28
Nanomotors Sense Local Physicochemical Heterogeneities in Tumor Microenvironments
Dasgupta,D.,Pally,D.,Saini,D.,Bhat,R.,Ghosh,A. Angewandte Chemie International Edition.2020,
Maneuverability of Magnetic Nanomotors Inside Living Cells
Strengths
- The Theranautilus team are pioneers in implementing magnetic manoeuvrability of nanostructures in biological systems.
- Current medical procedures cannot reach the required depths to kill bacteria. Proof of concept: they have already demonstrated drug delivery using nanobots in the dentine tissue of human teeth.
- Successfully demonstrated drug delivery inside live Wistar rats using nanorobotics technology.
- Quick route to market.
- Teeth are ideal for testing new cell-based treatments. Dental pulp is one of the few areas where stem cells are still found in human adults. Could provide the proof-of-concept to expand into other regenerative medicine therapies.
Risks
- Risk associated with novel technology.
- Nanobots have been shown to be magnetically guided down dentinal tubules, but no evidence for stem cell hybrids being able to so far.
- Adoption of the technology to replace current therapies might prove difficult.
Senior Review Digest - Quantitative
Below are the average scores out of 5 per category from 4 reviewers.
Average Scores
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Novelty and impact: 4
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Feasibility and data: 2.75
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Relevance: 3.5
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Science team: 3.5
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Market advantage: 3
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IP Potential: 4.5
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Conviction: 1,4,4,2 = 2.75
Senior Review Digest - Qualitative
Each reviewer was asked whether they would endorse the project, below are their answers.
Reviewer 1
In sum, the idea of guiding cells with magnets in vivo is exciting. However, this team has not demonstrated an ability to move the biological aspects of the project forward in a meaningful way. I would suggest that they recruit collaborators with the established necessary experience.
Reviewer 2
Theranautilus’s answers to my open questions are satisfactory and acceptable. Although a detailed business plan and research expenditure plan (salaries, experiment costs, etc.) still need to be included, Nevertheless the project has made valuable progress in the past months with new wet-lab data and technical upgrades. They have also successfully obtained a highly competitive government grant for the project, which validates their approach and gives a good platform to the team to run the project successfully.
I suggest sending the proposal for community votes.
Reviewer 3
The applicant did a good job giving thorough and informative responses to the reviewer critiques. I now understand the logic of the business plan and therapeutic plan better than I did before. I really like the technology and therapeutic plan. My biggest concern is with the logistics that would be required by the business plan. At least in the USA, dentistry is completely decentralized. Effectively, dental records are barely even shared between offices. I can’t even imagine the logistical nightmare of collecting teeth sometime between age 5 and 20 and then saving cells until the patient is 60 and needs the stem cells for a root canal. But, the technology is one of the best autologous cell technologies that I have seen. So I hope that the inventors can find a way to make it work economically and logistically someday and creative business people have a long time to figure that out while they perfect the technology.
Reviewer 4
I would recommend a conservative funding model based on clear milestones for this technology. This is due to the novelty of technology, but there is not enough concrete evidence to support that this could/will work in DPSCs.
- Agree
- Revisions Requested (Detail in Comments)
- Disagree
