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

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.

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.