Current research - Mr H A Mann & Professor Alex Seifalian
The Novel Use of Stem Cells & UCL Nano-Composite Material for Construction and Enhancement of Tendon, Ligament and Cartilage Repair
The non-biodegradable nanocomposite materials, based on poly(carbonate-urea)urethane (PCU), demonstrate hydrolytic and oxidative stability in vitro15 and viscoelasticity characteristics to biological vessels in vivo16,17possess similar This is combined with Polyhedral oligomeric silsesquioxanes (POSS, (RSiO3/2)n). POSS has a unique cage like structure with nanoscale dimensions (1.5 nm core) to create nanostructured hybrid materials. This has ben patented by Prof Alex Seifalian - Co Researcher.
Current Clinical Apllication & Use
This nanocomposite material has been used by Professor Seifalian to create the worlds first completely synthetic windpipe at the Royal Free Hospital. The nanocomposite material and stem cells harvested from the patient’s bone marrow were placed into a bio-reactor allowing the polymer to be seeded by the patient's tissue and creating an synthetic trachea. The trachea was transplanted into a patient whose own windpipe was invaded by cancer. The operation was done in Sweden at the Karolinska University Hospital in conjunction with the Karolinska Institute.
Since then the polymer has been implanted as nasocilllary lacrimal duct conduits, vascular implants and heart valve material. The material is also undergoing clinical trials for its use as a coronary artery bypass graft at the UCL Heart Hospital, and as a vascular access graft at Royal Free Hospital in August 2013 funded by the Wellcome Trust. In addition, it is also undergoing pre-clinical trials as a transcatheter heart valve. See pictures below
Aim and Hypothesis:
Our aim is to determine whether Mesenchymal Stem cell and UCL Nanocomposite material (POSS-PCU) can be used to (a) create ligament & tendon, augment and (b) enhance the repair of tendon, ligament and cartilage.
To date, to the best of our knowledge, no literature exists on the use of nanocomposite material composites in tendon / ligament repair and augmentation, nor as a biological extracellular matrix scaffold in orthopaedics and musculoskeletal medicine.
We aim to
1. Undertake Laboratory biomechanical testing to assess the mechanical properties
2. Animal Studies
3. Creation of ligament / tendon / cartilage
4. Human Clinical Trials
There are two phases to this project. The initial phase involves an array of animal studies with various arms and controls. We aim to apply Mesenchymal stem cells directly to the site of injury with our scaffold material POSS-PCU. Mesenchymal stem cells are able to differentiate into a variety of specialised mesenchymal tissues, including bone, tendon, cartilage, muscle, ligament, fat, and bone marrow stroma. They will be harvested from bone marrow. The stem cell and POSS-PCU biomaterial will provide both immediate mechanical strength as well as biological assistance through differentiation of the stem cells. Such tissue will heal tendon loss or replace severely degenerated regions.
Ultimately whole body tissues will be constructed in the laboratory and subsequently implanted into patients.
This will require the appointment of an experienced Masters student to undertake various projects designed by Professor Alex Seifalian and myself. The second phase of study would be clinical trials in patients recruited from my practice and other consultants.
Tissue engineering is an extremely promising technique that aims to solve the problem of safe and viable biomaterials in orthopaedics, by producing viable artificial ligament, tendon substitutes or augments in the laboratory conditions with the potential of transplantation to the patients with a high success rate. The key strategy is Bio-mimicry. To mimic the structure as well as function of the native tissue eg Achilles tendon augmented repair, Anterior Talo-Fibular ligament repair, the interface is a great challenge and multiphased scaffolds constitute a promising option to fulfill this need. The applications of this material in musculoskeletal medicine are therefore vast and potentially revoloutionary.