Tissue-Responsive Robotic Implants for In Vivo Mechanostimulation-Based Tissue Regeneration (Tissue-RIMOTE)

Lead Research Organisation: University of Sheffield
Department Name: Automatic Control and Systems Eng

Abstract

Conditions such as long-gap oesophageal atresia (LGOA) and short bowel syndrome (SBS) are two examples of chronic paediatric cases of gastrointestinal tissue reconstruction where up to two thirds of the oesophagus and bowel, respectively, may be missing. These are among the most complex and devastating paediatric anomalies that have a life-long debilitating effect on patients. Their current treatments are not widely available, are complex, primitive, long-term, and have disputed outcome quality. Families and surgeons have long sought an effective treatment to improve these patients' quality of life.

The proposed project aims to initiate an ambitious research agenda for a novel technology for the repair and reconstruction of soft tubular tissues inside the body using robotic and tissue regeneration principles. The underlying technology unifies the fields of tissue engineering, surgery and medical implants into a new concept of 'robotic implants'. The proposed robotic implants are one-size-fits-all linings for tubular tissues that enable autonomous tissue-responsive mechanical interaction with tissues to induce their growth.

Based on evidence from cell biology studies and clinical practice showing how tissues respond to mechanical stimulation in vivo, the proposed robotic implant applies gentle force directly to tissues to induce growth through cell proliferation. Thus, these robotic implants deliver controlled, long-term, customisable and optimal reconstructive therapy for tissues in an unprecedented way. The proposed technology has the potential to restore patients' mobility and social activity, as well as reduce hospitalisation and post-surgery complications, treatment and costs.

This proposal has a pioneering focus: to develop the design, fabrication and control of robotic implants that can physically and physiologically adapt to the changing properties of tissues and stimulate their growth. These robotic implants will consist of fundamental, compact and functional elastomeric strands that can be assembled into an architecture that can elongate with the growing tissue and apply controlled, directional mechanical stimulation to the tissue.

This project is the basis of an exciting interdisciplinary research framework that will allow communities of surgeons, biologists, tissue engineers and tissue mechanics researchers to investigate basic mechanisms of tissue growth and understand the relationships among tissue strain, tissue regeneration and inflammatory responses. In particular, the technology to be developed in this project will be a precursor clinical device for LGOA and SBS. This project also launches an investigation into soft robots that physically adapt and perform inside the body, which is imperative for tissue regeneration and growth as well as for wearable technologies that need to adapt to children's developmental stages.

Planned Impact

Society. The incidence of paediatric chronic gastrointestinal conditions in Western Europe has been increasing, e.g., incidence of inflammatory bowel disease (IBD) in the UK is 10 in 100,000 live birth (2018), the highest in Europe. In most of these cases, surgery is needed to remove the diseased tissue. The therapies to improve digestion after significant loss of tissue are complex and heroic, yet suboptimal. Two therapies, used in long-gap oesophageal atresia (LGOA) and short bowel syndrome (SBS) conditions, are exemplified. LGOA: is a disease characterised by an incomplete oesophagus, with an incidence of 5 in 10,000 live births in the UK. The most successful surgical technique (Foker technique) consists of attaching sutures to the oesophageal stub ends, to pull them for weeks to elongate them. The baby is sedated in the Intensive Care Unit (ICU) for a month, and hospitalised for more than 6 months. It is the most morbid paediatric surgery, only performed by highly trained surgeons. SBS: is a condition associated with partial loss of the bowel. It has an incidence of 9 out of 100,000 live births in the UK, with a high mortality rate (30%). The treatments often target the dilation of the organ. The child is dependent on parenteral nutrition (PN, i.e. intravenous feeding) for a lifetime, leading to impaired growth and severe diseases.
This project promises an optimal, controlled-at-all-times tissue growth. It will improve patients' and caregivers' quality of life by eliminating the morbidities of these conditions and enabling at-home therapy. The technology can be used by more surgeons as the surgical complexity is reduced. It also promises to remove patients' dependency on PN.

Economy. This project yields the precursor of a medical device for the treatment of LGOA and SBS, and equipment for tissue engineering. The care of patients with chronic conditions is expensive and requires a long-term commitment by trained individuals. The Foker technique costs £900,000 per patient and it is only available in the US. It costs the NHS an estimated £70m per year for alternative treatments, e.g., jejunum grafts. The proposed technology can drastically reduce this cost by 80% overall and the stay in the ICU and hospital by > 60%. The cost for SBS patients exceeds £23m yearly; most costs are in-hospital and home-care charges. By reconstructing the short bowel, these costs are reduced by >65% for a year. Later, they can be fully cut. Considering similar paediatric conditions, e.g., IBD, volvulus (cancer not included), the proposed technology could save the NHS about £160m yearly. The device could also serve as an adaptive scaffold in bioreactors for in vitro tissue engineering. It could also act as an active sensing sleeve on surgical robotic manipulators. Such technology can be licensed and sold on a growing market of bioreactors and surgical robotics to produce a significant impact on a 5- to10-year time scale.

People. This project will have a positive impact on the careers of the PI and PDRA. They will both gain additional experience in the translational aspects of in vivo mechatronics, soft physically-adaptive robots and autonomous tissue repair. The exposure to the clinic and medical industry will help the team build a larger network of collaborators for future funding proposals. The EPSRC grant is an important step in the PI's academic career, helping her consolidate her new lecturer position and raise her international profile in medical robotics.

Knowledge. This interdisciplinary project will advance the state-of-the-art research in surgical robotics, soft robotics and tissue regeneration, which are areas of great importance for the UK. The findings of this project will also affect closely related research fields, including in silico tissue medicine and prosthetics. The research impact includes scientific advances about physically-adaptive robots inside our bodies and novel techniques in tissue engineering and surgery.

Publications

10 25 50
publication icon
Atwya M (2020) Flexible and Expandable Robot for Tissue Therapies - Modeling and Design in IEEE Transactions on Biomedical Engineering

publication icon
Damian D (2020) Regenerative robotics in Birth Defects Research

publication icon
Perez Guagnelli E (2020) Characterization, Simulation and Control of a Soft Helical Pneumatic Implantable Robot for Tissue Regeneration in IEEE Transactions on Medical Robotics and Bionics

publication icon
Pontin M (2020) A physical soft tissue growth simulator for implantable robotic devices in IEEE Transactions on Medical Robotics and Bionics

 
Description There are a couple of significant achievements from this award:
- we produced a soft device featuring a 3D arrangement of ballooning membranes whose extension (more than 300%) at pressure inputs as low as 30kPa makes it one of the most effective soft actuators in the field
- we produced a conductive hydraulic system for soft robots, thus achieving sensing and actuation at the same time. The sensing capabilities can be adjusted and enhanced through a replenishable fluidic circuit.
Exploitation Route The current outcomes can be taken forward in a number of ways: (1) advancement to a clinical device for tissue regeneration using mechanical stimulation; (3) development of sensorized hydraulic soft robotic systems; (3) development of resilient mechanisms for soft robots.
Sectors Education,Electronics,Healthcare,Manufacturing, including Industrial Biotechology

URL https://sites.google.com/site/danadamian/
 
Description The findings have been used as follows: (1) Demonstrators for public and specialist audience engagement: We created demonstrators and showcased them in workshop as well as an open lab visits to our partners and stakeholders. We also demonstrated our technology in virtual innovation hub events, and published videos on our lab's youtube channel. (2) Involvement in outreach events, e.g., STEM 2020, Departmental Open Days, where results of the project have been shown. (3) Involvement in dissemination activities, e.g., clinical conferences (Child Health Tech Conference 2020), robotics conferences (IEEE ICRA, Embodied Intelligence Workshop), industrial networking (EPSRC Strategic Task on Soft Robotics).
Sector Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Policy & public services

 
Description University of Cambridge 
Organisation University of Cambridge
Department Department of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Meetings to write proposal and plan workshops
Collaborator Contribution Meetings to write proposal and plan workshops, invitations to help organise workshop, and participate in workshop
Impact Invitation to speak and chair forums at the Embodied Intelligence Workshop 2021 (multidisciplinary)
Start Year 2020
 
Description University of Firenze 
Organisation University of Florence
Country Italy 
Sector Academic/University 
PI Contribution Meetings for a collaboration and grant writing
Collaborator Contribution Meetings for a collaboration and grant writing Discussing design requirements for technology of this grant
Impact Project Proposal under review.
Start Year 2020
 
Description University of Oxford 
Organisation University of Oxford
Department Department of Engineering Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Meetings to write research proposal
Collaborator Contribution Meetings to write research proposal
Impact The collaboration is multi-disciplinary Grant proposal write-up leading to submission
Start Year 2020
 
Title HBMA 
Description A soft actuator that shows hyperelastic elongation (~300%) at as little as 30kPa. 
Type Of Technology Physical Model/Kit 
Year Produced 2020 
Impact Two journal publications that are conditionally accepted, and a conference paper in ICRA 2021. 
 
Title Physical simulator of tissue growth and stiffness 
Description A physical simulator of tissue growth and stiffness, to be used for benchtop tests to verify robotic implants and in vivo devices 
Type Of Technology Physical Model/Kit 
Year Produced 2020 
Impact A journal paper in IEEE Medical Robots and Bionics 
 
Title Robotic bioreactor 
Description A device that allows closed loop adjustments and measurement of traction force on the in vitro construct 
Type Of Technology Physical Model/Kit 
Year Produced 2020 
Impact A peer-review conference paper in the proceedings of ICRA 2021 
 
Description ACSE Taster Days 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The activity consisted of a talk about Dr Damian's group's research and Q&A
Year(s) Of Engagement Activity 2020
 
Description Project Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact max 10 professionals, e.g., veterinary staff, surgeons, attended a meeting where we present our project developments, and they provide input, further guidance about the next steps
Year(s) Of Engagement Activity 2020
 
Description STEM 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The activity consisted of a taster talk about my research and Q&A
Year(s) Of Engagement Activity 2020