Team:KCL UK/Entrepreneurship

Entrepreneurship

Introduction

The unique, inventive nature of our approach is strongly linked to the interdisciplinary and multi-faceted nature of our team. Our team sees the culmination of entrepreneurial students from the life sciences, with students studying subjects including Biomedical Science, Biochemistry, Molecular Genetics and Neuroscience working alongside Biomedical Engineers. The result of this interdisciplinary, therapeutics-focused team is the convergence of synthetic biology and 3D bioprinting, resulting in the creation of a novel approach for spinal cord injuries (SCI). We are passionate about entrepreneurship and this has led us to design a project aligned to the possibility of commercialisation and the potential for it to become a start-up. We have spent time researching the steps we would need to take to achieve this and we have detailed this below as part of our approach to explore excellence in entrepreneurship. We have designed our approach to highlight the necessary steps we would need to take in order to turn our project into a start-up company. In addition to entrepreneurship related to Renervate, we are passionate about sharing our knowledge and interest in entrepreneurship. We have designed a competition that shares our passion for Synthetic biology and has placed an emphasis on exploring entrepreneurship and business skills. We have also contributed a summary of the steps needed to commercial an iGEM project, for future iGEM teams to utilise.

Identification of Market Gaps, Key Players and Stakeholders

Identifying a gap in the Market

In the UK approximately 2,500-3,500 people are diagnosed with SCI every year, with a total of 50,000 people living with it ( Spinal cord injury and how it affects people | Back Up , n.d.). As a consequence of SCI, over 2.5 million people worldwide live with paralysis ( The Research , n.d.). Beyond its physical symptoms, SCI affects one’s mental and financial wellbeing, the impacts of which may extend to the patient’s family and friends. Due to the complexity of the CNS and the little knowledge of its regenerative abilities, much remains unknown about SCI and how to treat it. Although there are a few successful treatments that are currently being used to treat SCI (such as surgical decompression and immobilisation of the spinal cord), there are presently no licensed treatments that serve to reverse the damage to the spinal cord created by the injury. This is precisely the gap which we aim to fill. We plan on precisely filling this gap by providing a treatment that reverses the damage created by SCI. Following extensive research on the pathophysiology of SCI and axonal regeneration, we have designed a scaffold that physically bridges the gap between the severed axonal pathways thus potentially restoring motor and somatosensory function. More detail on our design process can be found on our Project Design page .

Identifying our Stakeholders

In order for our project to become a successful start-up, we had to do an analysis of who our potential stakeholders were. Stakeholders are anyone who will have an interest in our project/start-up and it’s affairs. Firstly, when designing our lean business plan, we had a brainstorming session and identified two potential stakeholders: the SCI patients and the surgeons who would be implanting our device. Following this meeting, we arranged a meeting with the Spinal Injury Society where we were able to talk to patients about their struggle in an ethical way. This meeting helped us to identify the patient’s carer as another potential stakeholder as our device would indirectly affect them. Furthermore, we also identified insurance companies, private hospitals and public health bodies (such as the NHS) as stakeholders as they would be the organisations paying for our product. Finally, we also identified neurosurgeons who treated SCI as another stakeholder as they would be the ones implanting our device into patients.

Identifying our Customers

We have identified our customers as individuals presenting with cervical chronic spinal cord injuries. These patients present with the formation of a syringomyelia (fluid filled cavity) in the cervical-thoracic spine (a region of the spine that is likely to cause devastating paralysis upon injury (Krebs, J., et al.). This patient subset requires immediate attention due to the current lack of treatments on the marker aimed at treating post-traumatic syringomyelia. Our product aims at providing a bridge across this cavity which supports axonal regeneration across the lesion.

We also identified the NHS as a potential customer so we arranged a meeting with Dr Rachel Sparks where we discussed increasing accessibility of our product to the NHS. During the meeting, we concluded that it would be appropriate to set ourselves the target of getting our product listed in the National Institute for Health and Care Excellence ( NICE ) - an organisation that creates proof-based guides about many areas in the medical industry. In order to do so, we must ensure the type of assessment that is carried out for medical devices intended to aid SCI recovery is done in line with NICE guidelines. The NHS uses guides created by NICE when acquiring new devices and considering their coverage of offered treatments (NICE, n.d.).

Intellectual Property

Patents are a type of Intellectual Property (IP) which is described by the European Patent Office as ”Patents protect technical inventions in all fields of technology. They are valid in individual countries, for a specified period. Patents give holders the right to prevent third parties from commercially exploiting their invention. In return, applicants must fully disclose their invention. Patent applications and granted patents are published, which makes them a prime source of technical information.”( EPO - Home , n.d.). However, obtaining a patent for a product is a time-consuming process which tends to involve an elevated cost. Another important consideration is that to obtain a European Patent, it must not be known to the public in any form (EPO - Home, n.d.), therefore, after the first public disclosure, you can no longer file a patent.

We carried out a patent search to find any similar products and to ensure our product was patentable. We used the search engine Espacenet to search for the existing patents by using keywords which included “spinal cord”, “spinal cord injury”, “spinal injury”, “cervical chronic” “scaffold”, “axonal regeneration”, “PCL”, “polycaprolactone”, “mussel foot protein”, “bioadhesive”, “synthetic protein”.

Landscaping Analysis

We have conducted landscape analysis to assess the risk of patent infringement - Two similar patents were identified:

  • This first patent “Nerve conduit capable of improving axonal regeneration orderliness and preparation method thereof ( CN108187148A )” describes a bio-architecture consisting of a porous channel which stimulates axon regeneration. Request for examination was entered 17/07/2018 and is still under assessment. It has the aim of reducing mismatch between regrowing axons and their targets by using inhibitory molecules. Although this patent uses a channel like structure, the macro architecture differs greatly from ours in that we are using a scaffold with an open path and core structure, whereas they have implemented a continuous porous tube. Moreover, we will be coating our scaffold in a synthetically modified variant of Pvfp-5 Beta after performing mutagenesis on it to increase favourable physicochemical properties. This patent does not describe any bioadhesive element and therefore is unlikely to pose any infringement issues.

  • The second patent that we identified to have similarities to our project was “ Preparation and application of nano-magnesium hydroxide regionally polylactic acid-caprolactone coated stent for repairing spinal injuries ( CN110585481A )" which describes a porous stent, filled with nano particles, to encourage bone and axon regrowth. Request for examination was entered 17/07/2018 and is still under assessment. This patent seems to have more similarities to our invention than the first, however is still able to be distinguished. The stent is coated and saturated with nano particles which act to treat spinal cord injury in particular. Both our inventions share the same niche in terms of the targeted disease, as well as both coating a PCL scaffold to be inserted. Although we are using PCL to make our scaffold, this is a very popular bioengineering material and is certainly not the feature defining the novelty of our invention. With regards to the coating of the scaffold, their focus is in bone and nerve regeneration by using nanoparticles. We are therefore certain in the uniqueness of our scaffold as we will have created a synthetic protein polymer to coat the PCL with the aim of providing mechanical strength as well as a substrate for growing axons to adhere to.

Overall, this patent search confirms there are no obvious similar patents since even the two found above are different enough from our invention.

Our Potential Patent

As a consequence of our scaffold having been already produced by other investigators, we will not be able to patent the scaffold. Since our product contains two components, the scaffold and bioadhesive layer, we will have to patent our product as “a mussel foot protein based bioadhesive covered scaffold”. Since we intend to design the parts for the thermostable version of the protein that will cover the scaffold during phase 2, there will have been no public disclosure yet and therefore the parts of the thermostable protein will be patentable. We aim to file the patent next year before handing in our project to iGEM and we plan on starting discussions with the King’s College London Intellectual Property Department to ask them if they will aid us through this process. Strategically we would like King’s College London to file the patent with us and list us as inventors because that way the project will have the backing of a University with a strong focus on therapeutics.

The thermostable MFP we will develop next year will be a brand new protein therefore there will be no patents for it. However, we will need to check again next year for patents of PCL scaffolds to treat SCI with a layer of bioadhesive. This could conflict with our patent request.

Competitor Analysis

We carried out a market research to find if there were any similar businesses already existing. We found a two with similar products:

NeuroStimSpinal is an ongoing project that began in 2019. Their project focuses on spinal cord injury patients and they attempt to treat them using a graphene based material scaffold provided with an electrical stimulator and combined with adipose derived decellularized tissue. The structure of the scaffold along with the electrical stimulation is intended to promote the growth of damaged tissues (NeuroStimSpinal, n.d.). Similarities of this project with Renervate include the aim to treat spinal cord injuries and that the scaffold is partially 3D printed.

INVIVO Therapeutics has developed a custom made 3D printed scaffold made of PLGA. They have already completed clinical trials for their INSPIRE 1.0 scaffold and are already conducting clinical trials on the INSPIRE 2.0 scaffold. They are investigating the possibility to combine their scaffold with therapeutics, stem cells and electrical stimulation (InVivo Therapeutics – Redefining the treatment of spinal cord injury, n.d.) ( InVivo may use 46 3D printers to make spinal scaffolds , 2020).This product is the most similar by far to Renervate’s scaffold and the major difference lies in our use of the MFP.

During phase 2 we will continue to look for companies which develop between now and next year and construct a more in depth competitor analysis to learn from these companies.

CE Certification Strategy

The Johner Institute 6-step guide to place medical devices into the European market provides a simple explanation of the steps to follow that we have placed in the diagram below (Johner Institute, n.d.). We were able to partially work through the two first steps:

Definition of Intended Product

Annually, between 250,000 and 500,000 individuals worldwide suffer from a spinal cord injury (SCI) ( Spinal cord injury , 2013). SCI is characterised by damage to the spinal cord followed by a complex pathophysiological response and loss of neuronal function below the site of injury. The limited regenerative abilities of the CNS combined with the inhibitory environment created by the glial scar at the affected area pose numerous challenges to restoring function. Working towards a therapy for cervical chronic SCI, we have designed and modelled a biodegradable scaffold composed of polycaprolactone, that incorporates a synthetic mussel-foot protein based bioadhesive coating, to encourage axonal attachment, and can be produced using 3D-bioprinting methods. Our scaffold is customisable so that its size can be modified depending on the patient’s injury and contains the necessary micro- and macro-architectures predicted to topographically encourage axonal regrowth and withstand the mechanical forces in the spine. Further modifications can be made to the scaffold to better adapt to a patient’s need such as using stem cells from the patient or by creating a drug regime within the scaffold. More information about the possible use of stem cells or drug delivery systems can be found on the Engineering page .

Relevant European Regulations

Below outlines how our product will be classified by and conform to the Medical Device Regulations (MDR) legislation as published by the European parliament in 2017.

General Defining Terms from the MDR

  • Subsection 1, Article 2: Our device is an implant to be used in human beings for treatment, alleviation of or compensation for an injury.
  • Subsection 3, Article 2: Our device might be considered as a custom made device in later stages but since we intend to initially mass produce it, with the exception that its size will be adapted to the patient’s injury, it would not be considered a custom piece currently. During the meeting with Dr Rachel Sparks, she suggested that strategy in which we’d argue against our scaffold being a custom made device, since custom made devices cannot bear the CE marking. UK hospitals can only buy medical devices with the CE marking or for devices without the CE marking, they must apply for use as part of a research study which must be approved by MHRA, which would limit its use in hospitals.
  • Subsection 5 of Article 2: Our device falls within the definition of implantable device and it is to remain in the patient after the procedure.

Classification from Annex VIII MDR

  • Long term (Chapter I, Subsection 1.3)
  • Surgically invasive (Chapter I, Subsection 2.2b)
  • Class III (Chapter III, Subsection 5.2 - Rule 6)

Quality management system considerations

Since we are using a 3D printer to produce the scaffold before coating, we have examined the criteria which require medical applications to apply the IEC 62304. As the 3D printer is not itself a medical device, nor does it constitute an integral or embedded part of the final medical device, it will not be necessary to apply the IEC 62304 (Bellairs, 2019).

Dr Prashant Jha

We organised a meeting with Dr Prashant Jha where he explained several aspects of the process to obtain a CE certification. He also advised us in the following strategy to place the medical device on the market. Since we are aiming to place our device onto the EU market as soon as possible, we will submit an application for a CE certificate of a (3D printed structure / chemical / experimental structure) which would take less time to obtain and have a lot less requirements instead of an application for an investigational device. Going through the investigational device pathway would also imply that we would have to notify and pay a fee to the Medicines and Healthcare products Regulatory Agency (MHRA) ( Notify MHRA about a clinical investigation for a medical device , 2014) as well as complete a set of documents required for the application though the Integrated Research Application System IRAS before we are able to begin any clinical investigations. Once we have obtained the CE certification, we would begin clinical investigation. Following the completion of this, we would then have to resubmit the application, but this time for a medical device.

Clinical Investigation

Clinical investigation needs to be carried out to ensure the proper functioning of the device and to identify and mitigate risks associated with the device. The requirements for clinical investigations are found in annex XV of the MDR. We had arranged a meeting with Dr Prashant Jha, we went over the typical features of a clinical investigation and created a plan below, based on his input we received, to evaluate the functionality and safety of our device. This process is estimated to take between 5 to 10 years to be completed, assuming that there are no setbacks.

Due to the ongoing pandemic, we were unable to access the lab and thus are unable to produce any data for cell based in vitro studies this year. However, we did put a big emphasis on the modelling and mechanical testing of our product. So far, our bioprinting team has been able to successfully model the degradation of our PCL based scaffold and conducted a stress test of the scaffold. Their next steps would be to conduct stress accounting for factors such as walking, sitting up and everyday activities and movements of the spinal cord. Furthermore, the mussel foot protein team have done preliminary research for the modelling of our protein adherence and mutagenesis studies using iGAM (a modelling software developed by a previous iGEM team) and we plan on conducting these studies next summer.

Dr Prashant Jha suggested a set of clinical investigation milestones we should follow to reach human trials, starting by conducting in vitro studies to prove that the scaffold does not block neuronal membrane channels and the attachment of our protein to the scaffold (this would require access to a laboratory with equipment required to conduct electron microscopy). Following this meeting, we decided to generate several protocols for in vitro studies that will be conducted in phase II of our project. Firstly, we have already designed a co-expression vector system for the production and polymerisation of our Pvfb-5ß protein into a bioadhesive polymer. This polymer will then be used for surface adsorption and adhesion tests which would produce data to support the efficacy of our bioadhesive polymer. We had also arranged a meeting with Dr Jaimie Lauzen Alcón who has suggested we do in vitro studies to prove that our product is not immunogenic and toxic. He suggested that we should conduct in vitro studies to test the toxicity of our protein by incubating the protein at the same concentration used to coat the scaffold with fibroblasts (HeLa), lymphocytes (P/3/88) and macrophages (RAW) at physiological conditions. We will then check the cell samples to test for any degree of cell death. We are in the process of creating protocols for in vitro studies such as “Testing axonal/neurite outgrowth” and “Testing the immune response”. For more details about our selected Protocols have a look at our Engineering page. The data collected will be used to demonstrate that our scaffold is not cytotoxic or immunogenic and provide optimal conditions for the neurons to grow on.

If our in vitro studies prove successful and the data collected proves the efficacy of our device, we will apply for animal trials. Our animal trials will test the efficacy and safety of our product in a lower mammalian model (eg. Mice) and then in a higher mammalian model (eg. Chimpanzees). If there are no setbacks during the animal trials, we will then need to test our product in human trials. Since it would be unethical to test our product in healthy human candidates or to give a placebo to SCI patients, we will have to test the safety and efficacy of our scaffold using public data about SCI patient recovery as our control group and consenting SCI patients as our trial group.

Timeline

We have created a 10 year forecast of the steps we would need to take in order to enter regulatory pathways. The timeframes are based on the estimations Dr Prashant Jha gave us; however, this chart is optimistic in the sense that it does not account for failure or setbacks in in vitro studies, animal trials and human trials. This Gantt chart also does not account for the period of time required for the necessary paperwork required to enter clinical animal and human trials.

Reports from MAUDE Database

After Dr Rachel Spark’s recommendation in the meeting we investigated the Manufacturer and User Device Experience ( MAUDE ) database which is a public database from the USA that is used to record any issues with medical devices. By using the MAUDE we intended to find issues from similar devices that we might have not thought of. We found many reports of electronic implants malfunction, but none of the reports described an implant like ours which would be absorbed over time within the spinal cord. Nonetheless, from the selected reports we were able to obtain a series of safety concerns that we should attempt to mitigate in our device. Below the reports are referenced by report number of the MAUDE database.

Medical Malpractice

  • Report “ MW5095987 ” describes medical malpractice when recommending the treatment to a patient, who not only did not require the treatment but also had to be declared disabled due to the treatment.
  • Report “ 1030489-2019-00799 ” describes medical malpractice due to a lack of concern of the patient’s symptoms in the follow up after the surgery to place the implant. The patient became disabled as a result.

Medical malpractice is a major concern for this project and to mitigate it as much as possible we would suggest to host seminars and trainings for new surgeons who would like to learn how to implant our scaffold. Before being allowed to carry out the implantation procedure, the trained surgeons will have to go through performance assessments on cadaveric specimens or phantoms. To further reduce this risk we want to produce a clear surgical implantation protocol that surgeons will be able to follow. Reflecting on the reports we should also consider hosting seminars for doctors who will prescribe our scaffold as a treatment so that they do not mistakenly prescribe it to patients who do not need it. Furthermore, Renervate highly encourages the use of non invasive therapies since the implantation of our device carries risks which might be higher than the benefits it brings in some situations. To mitigate risks relating to post operatory care we should ensure that a care protocol which dictates certain services the patient will have access to is put in place and that all hospitals we are associated with can follow it.

Nerve damage due to the device

  • Report “ MW5096383 ” describes a case of an electronic implant in the spinal cord which overheated causing permanent damage and severe pain. Patient had to file for disability.
  • Report “ 3006630150-2020-03699 ” describes a case of a permanent implant that after being implanted it caused a loss of sensation in the lower limbs of the patient. Patient was able to rehabilitate after removal of the implant.
  • Report “ MW5094407 ” describes a patient that after implantation of the device in the spine, felt discomfort through her body. She had to turn the device off. Even after removal, the patient still has permanent nerve damage in all limbs as well as discomfort in her abdomen.

There is always a risk of medical devices possibly causing adverse effects due to multiple reasons, including misplacement of the device and immunogenic response. To reduce the risk of surgeons misplacing the scaffold we discussed a series of methods in the previous section related to medical malpractice. As for reducing the possibility of an immunogenic response, literature reviews have confirmed the biocompatibility of PCL and therefore the most likely element to cause an immunogenic response is the MFP. We will undergo extensive in vitro studies in order to understand the immunogenicity and neurotoxicity of our protein before we plan on pursing clinical trials. Furthermore, we will also strictly adhere to the guidelines of regulatory bodies which ensures the safety of our product and prevention of adverse effects such as an immune response. After reflecting on the data from the reports we can confirm that due to the location of the injuries we are trying to tackle, the implantation of the scaffold does carry the risk of causing irreversible nerve damage which can manifest in a large range of conditions. Currently it is uncertain how to mitigate this risk aside from providing training to surgeons.

Detachment of site of injury

  • Report “ 3010676138-2020-00042 ” describes the case of a patient whose implant detached and moved out of the implantation site.

Our scaffold will not only be small in size (of about 1 cm) but it will also be very light due to the high porosity and choice of material therefore reducing the risk of detachment. Furthermore, the MFP coat on the scaffold should ensure the anchoring of the device to the site of implantation. Nonetheless we should consider the possibility of the scaffold becoming dislodged and moving as a whole or in sections (since after some time, the scaffold might have degraded into multiple pieces). However, methods to mitigate this risk will have to be developed after the clinical investigations, only if it is concluded that detachment of our scaffold is a possible risk and that it might cause adverse effects.

Infection

  • Report “ 3007566237-2018-02339 ” describes the case of a patient who developed an infection after the implantation of a device.
  • Report “ 3007566237-2018-01893 ” describes a patient who developed meningitis after the implantation of a pump. The device had to be removed.

Infection is a risk that has to be considered in every surgical procedure and it is usually dealt with by prescribing the patient with antibiotics before and after the surgery. The report from the first bullet point discusses the use of an absorbable antibacterial envelope, and even though its use could be investigated for our scaffold during the clinical investigations, the fact that it is a layer that covers the whole surface of the implant would defy the point of using the MFP in the scaffold. However other alternatives such as adding an antibacterial component to the scaffold should be considered.

Interaction with nearby tissues

  • Report “ 1030489-2012-01690 ” describes the case of a patient who got implanted a graft filler with human bone morphogenic protein. Caused the fusion of the lumbosacral spine.

Our scaffold is intended to only interact with the damaged area of tissue where it is implanted, however early detachment of the scaffold while its MFP is still adhering to new surfaces could cause the tearing of tissues it attaches to while it moves. This nonetheless should be highly unlikely since after the implantation of the scaffold, the patient will have to be on bed rest and therefore the possibility of it detaching until it is fully anchored is very low. Another possibility is that an excess of MFP would diffuse out of the scaffold and stick the scaffold to other surfaces or stick other surfaces together. Mitigating this issue should not be difficult if the protocols for coating the scaffold that will be designed in phase 2, are followed correctly. Another possible risk is the calcification of our scaffold. The risk with the deposition of calcium around the scaffold is that it might interfere with the axonal regrowth by blocking the channels to the scaffold, and once the scaffold has completely degraded, the calcium deposits will remain, which might cause further problems in the spinal cord such as growth of the calcium deposits. The extent of both of these issues will be further investigated in the clinical investigation.

Business Plans

Lean Business Plan

We have summarized our current strategy to place our scaffold in the market in a lean business plan.

Alternative Business Plan

Following our meeting with Dr Travis Schlappi, we realised that we could not scale up our project by using injection moulding (a technique currently used to mass manufacture 3D printed diagnostic devices) due to the personalisation of our device to the patient’s injury size. We therefore developed an alternative business model where we are still able to personalise the scaffold specific to the patient but instead of producing the personalised scaffold ourselves, the 3D model would be sent to the corresponding hospital and printed in place. We could collaborate with a company who builds sterile manufacturing facilities to create small spaces in the hospitals with fully automated (no need for humans to enter the facility for it to work) sterile manufacturing facilities where a 3D bioprinter would be installed. As a company, Renervate would produce and distribute the MFP to hospitals and could provide the material for the printer (PCL). Hospital staff would have to be trained to learn how to check if the scaffold has been correctly printed and to create the layer of MFP over the scaffold unless we can figure a way to automate these two processes. To further simplify the staff’s task, a multi material 3D printing technique could be implemented, where the support structure of the print would be made of a water soluble material, in such a way that it would only need to be placed in a water solution to remove the support structure. Furthermore, we have also considered branching into the world of veterinary sciences if our animal trails prove to be successful. We believe that there is a big market as two of the most common pets are dogs and cats, which tend to suffer from SCI due to traffic accidents. More research, however, will need to be conducted on the regulatory pathways for veterinary devices.

Expanding our niche

We have explored how we could potentially grow Renervate as a company to tackle other types of spinal cord injury in addition to chronic, cervical spinal cord injury. Our scaffold treatment is only suitable for patients with chronic, cervical glial scar who suffer from paralysis, meaning patients with smaller glial scars, who do not suffer from paralysis as a result of their injury are unable to benefit from the scaffold treatment we have designed. We have researched alternative treatments for this subset of patients, as a prospect area we could move into in the future to grow our business. The most promising candidate for this additional subset of patients was proteases which promotes regeneration of the axons, even in the presence of the glial scar, which is less invasive and hence could provide a more optimal treatment for patients with smaller lesions. Our literature research has provided a foundation for the implementation of a non-surgical method of promoting axon regeneration post a spinal cord injury. Our current research suggests that ChABC will be the most effective in promoting axonal regeneration because it has already been administered as an intraspinal injection in animals, supporting it’s non-surgical implementation (Bartus et al. 2014). The leading alternative to ChABC is PP2A, which is less optimal as only activated with an agonist that is pumped. A pump is required to be placed over the cyst and pierces the dura, which is much more invasive (Cheng et al., 2015). We studied the different candidates for our proposed design of areas to expand into in the future, ensuring our final choice of prospective treatment did not further exacerbate the patient’s injury, always keeping our human practises in mind. The main current drawback with the ChABC is the thermal-instability (Day et al. 2020). Through identifying and mutating suitable residues, the thermo-stability could be improved. This would build on the mutagenesis studies we are undertaking in the phase two of our project when optimizing our MFP. Once the safety and validation testing has occurred successfully, the novel variant of ChABC could be utilized as a treatment to offer a non-invasive treatment for patients with smaller glial cells and symptoms which affect their lives, widening the market size and the subset of patients we would be working to assist.

Entering other markets

We considered scaling up our project into the US market by researching into the FDA system. Firstly, we arranged a meeting with Dr Jim Sterling where we discussed the fastest and cheapest way of obtaining an FDA approval for our scaffold via. The 5-10-K pathway. This pathway enables us to use a predicate device (an existing FDA / regulatory-board approved patent that is substantially similar to our project) to avoid going through the clinical investigation to prove the safety of our device, except for the part making our device different. If however, our device is completely new, we would have to see all trials from start to end and it would therefore be more expensive to obtain the approval. We also met with Dr Travis Schlappi about the possibility of going down the 510K pathway, however, he stated that this was not possible because our protein is synthetic and novel (and used for a class 3 medical device). Another reason for not being able to do so was because our mussel foot protein has only recently been identified and studied and there are no patents covering the protein.

Introduction to Entrepreneurial skills

As part of the inclusivity part of the project we developed a free biotechnology and synthetic biology entrepreneurial and innovation competition, called Biologix. With this program we hope we will be able to share our passion for entrepreneurship with students in their penultimate year of high school and encourage them to pursue a career in bioentrepreneurship. Biologix is a hands-on project where students will learn about the bases behind project development including entrepreneurship. More information about the Biologix competition can be found in the Biologix page.

Another resource we hope will help future iGEM teams to develop their entrepreneurship section or inform people interested in bioentrepreneurship is the guide we have created to place your product on the market. We created a generic guide to placing your product on the market based on the steps we planned out for our project. Due to the nature of our project being a therapeutic based project, we had to specialise certain steps to ensure the success of our project. Examples include looking at legislation surrounding development and release of medical devices into the market and also at regulatory bodies of medical devices such as MHRA and the FDA.

Conclusion

We are hopeful that our project is successful in taking off as a start-up company. The long-term effects of the success of our scaffold would have a wide reach as it would be one of the first regenerative medical treatments aimed at reversing the damage caused by spinal cord injuries in the cervical-thoracic region; thus directly impacting a subset of the 2,500-3,500 people diagnosed with SCI every year in the UK ( Spinal cord injury and how it affects people | Back Up , n.d.). However, since this treatment will only be available to recently diagnosed patients, we would have to be very mindful to the individuals living with SCI as it may give them a false sense of hope. Furthermore, we also hope that the research we have conducted may inspire others to take a multifaceted approach to treating diseases.

References:

  • Back Up. n.d. Spinal Cord Injury And How It Affects People | Back Up. Available at: (https://www.backuptrust.org.uk/spinal-cord-injury/what-is-spinal-cord-injury) Accessed 24 September 2020.
  • GOV.UK. 2014. Notify MHRA About A Clinical Investigation For A Medical Device. Available at: (https://www.gov.uk/guidance/notify-mhra-about-a-clinical-investigation-for-a-medical-device) Accessed 17 August 2020.
  • Invivotherapeutics.com. n.d. Invivo Therapeutics – Redefining The Treatment Of Spinal Cord Injury. Available at: (https://www.invivotherapeutics.com/) Accessed 15 September 2020.
  • Neurostimspinal.eu. n.d. Neurostimspinal. Available at: (https://www.neurostimspinal.eu/home) Accessed 16 September 2020.
  • plasticstoday.com. 2020. Invivo May Use 46 3D Printers To Make Spinal Scaffolds. Available at: (https://www.plasticstoday.com/invivo-may-use-46-3d-printers-make-spinal-scaffolds) Accessed 15 September 2020.
  • Spinal Research. n.d. The Research. Available at: (https://www.spinal-research.org/research) Accessed 24 September 2020.
  • Who.int. 2013. Spinal Cord Injury. Available at: (https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury) Accessed 24 September 2020.

Legal

  • Bellairs, R., 2019. What Is IEC 62304? Compliance Tips For Medical Device Software Developers | Perforce Software. Perforce Software. Available at: (https://www.perforce.com/blog/qac/what-iec-62304) Accessed 22 October 2020.
  • European Patent Office (EPO) (https://www.epo.org/) Accessed 16 October 2020.
  • Johner Institute, “Starter-Kit: How To Quickly, Easily And Safely Master The Medical Device Approval Process” (https://www.johner-institute.com/starter-kit/) accessed October 2020.
  • National Institute for Health and Care Excellence (NICE) (https://www.nice.org.uk/) Accessed 12 October 2020.

Scientific

  • Bartus, K., James, N., Didangelos, A., Bosch, K., Verhaagen, J., Yáñez-Muñoz, R., Rogers, J., Schneider, B., Muir, E. and Bradbury, E., 2014. Large-Scale Chondroitin Sulfate Proteoglycan Digestion with Chondroitinase Gene Therapy Leads to Reduced Pathology and Modulates Macrophage Phenotype following Spinal Cord Contusion Injury. The Journal of Neuroscience, 34(14), pp.4822-4836.
  • Cheng, P., Chen, K., Yu, W., Gao, S., Hu, S., Sun, X., Huang, H., 2015. Protein phosphatase 2A (PP2A) activation promotes axonal growth and recovery in the CNS. Journal of the Neurological Sciences 359, 48–56.
  • Day, P., Alves, N., Daniell, E., Dasgupta, D., Ogborne, R., Steeper, A., Raza, M., Ellis, C., Fawcett, J., Keynes, R., Muir, E., 2020. Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting. PLoS ONE 15, e0221851.
  • Krebs, J., Koch, H.G., Frotzler, A., 2015. The characteristics of posttraumatic syringomyelia. Spinal Cord 54, 463-466.