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Building on recent advances in cell-therapy research, the EU-funded BIOCAPAN project marks an important first step toward clinical trials, potential regulatory approval and the subsequent commercialisation of a novel system using tiny bioengineered microcapsules to restore the body’s ability to self-regulate blood sugar.
‘We have opened the door to future research on the path to a commercial product. Although there is still a long way to go to reach the final objective, the outcomes of BIOCAPAN prove that the technologies we have chosen are very promising,’ says project coordinator Frédéric Bottausci at CEA, the French Alternative Energies and Atomic Energy Commission.
‘The quality of life of patients will be tremendously improved since they will not have to think about or manage their disease on a daily basis: their blood glucose will be naturally adjusted by the transplanted microcapsules, and healthcare costs will be reduced,’ Bottausci continues.
The project results hold promise for a long-lasting solution to the therapeutic challenges of managing type 1 diabetes, a chronic condition characterised by high blood sugar that affects around 45 million people worldwide, including millions of children. If not controlled with frequent blood-sugar measurements, a carefully managed diet and injections of blood-sugar regulating insulin, the disease can damage the eyes, kidneys, heart and nerve endings and may even lead to premature death.
No more insulin injections
BIOCAPAN’s novel system would eliminate the need for daily management of the disease and regular insulin injections. Instead, the approach makes use of pancreatic cell clusters called islets of Langerhans containing β cells which, in healthy individuals, produce insulin in response to changes in blood glucose levels. Obtained from donor pancreases, the Langerhans islets are encapsulated inside bioactive microcapsules implanted in the diabetic patient to restore their body’s ability to regulate blood sugar.
The bioactive microcapsules measure less than a millimetre and are designed to recreate the natural microenvironment of the islet cells to enhance their biocompatibility, functionality and survival to achieve at least two years of insulin-injection-free treatment. Coatings on the capsules mask them from the patient’s immune system, eliminating the need for immunosuppressive therapy.
‘Islet transplantation is now a validated therapy for unstable diabetic patients who have difficulties managing the disease. The weakness of this therapy, in addition to the scarcity of donor pancreases, remains the long-term loss of functionality of the transplanted islets which leads to the need for repeat islet transplantation and lifetime immunosuppression, which is often associated with serious adverse effects,’ Bottausci explains.
‘Our approach is designed to address those challenges, focusing on a long-term solution for the patient’s body to be able to efficiently regulate blood glucose without the need for immunosuppressant treatment.’
Using innovative biomaterials
The microcapsules are made of an innovative combination of biomaterials, including alginates, a naturally occurring anionic polymer typically obtained from brown seaweed, mesenchymal stem cells derived from skeletal tissues, peptides coupled with alginate, and a functional protective anti-fouling coating.
A novel extra cellular matrix (ECM) – a network of macromolecules such as proteins and enzymes that provides structural and biochemical support to surrounding cells – mimics the natural pancreatic environment of Langerhans islets.
‘BIOCAPAN focused on creating a microenvironment within the microcapsules, reducing the size of the capsules, increasing their mechanical strength and optimising their surface condition. The formulation of the microcapsule, which we have patented, will help the survival of the implanted islets and thus increase the time during which the patient is insulin-independent,’ Bottausci says.He points out that some of the biomaterials have other potential uses. The anti-fouling layer, for example, could be used for the protection of many kinds of implantable devices, while the ultra-pure ECM can be used in bio-ink for 3D bio-printing systems. Similarly, a patented solution to automate the production of standardised microcapsules, ranging in size from a few tens of micrometres to a millimetre, has other potential applications, such as for genetic screening systems or bio-printing, in addition to the efficient encapsulation of Langerhans islets for diabetes treatment.