REGROWING BONE NATURALLY

Bioengineers and surgeons have been making waves in bone tissue engineering, allowing them to heal and regrow broken bones without the need for bone grafts or metal plates. Early last year, 18-year-old Nikita (not her real name) was seriously injured in a car accident in India that killed both her parents. The Indian teenager’s skull was shattered in the crash and she had a large, palm-size hole in her skull. A desperate uncle took her to neurosurgeon Sharan Srinivasan in Bangalore. Dr Srinivasan took one look at the injury and called materials engineer Prof Teoh Swee Hin in Singapore, an expert in coaxing bone to grow back on biodegradable bone plugs and scaffolds. Prof Teoh, now at Nanyang Technological University, and his team put together a spider-web like titanium frame, which held in place sheets of flexible, biodegradable scaffolds infused with Nikita’s own bone marrow. Besides producing red blood cells and some white blood cells, bone marrow also contains the cells that are, or will turn into, the main component of bone. Now, a year and a half on, the hole in Nikita’s skull has healed. “I went to Bangalore in August, a year after the surgery, and I could not recognise her,” Prof Teoh said. Around the world, there have been about 10 such cases in the past three years, Prof Teoh said. Bone tissue engineering is used to help patients who have lost bone to cancer – in accidents, or in some types of brain surgery which involve drilling holes in the skull - to regrow and remodel damaged bone. The technology, which started a decade ago with producing tiny bone plugs the size of a five-cent coin, has now advanced to a stage where it could provide a safer, less painful treatment for people who have larger areas of bone damage. Experts from Singapore and around the world were in town for the sixth Bone Tissue Engineering Congress, or Bone-Tec, at Nanyang Technological University earlier this month. At the congress, Prof Teoh presented a surprising new finding: Bone grew back most where the curved titanium frame was exerting force on the surrounding area. It is not clear exactly why bone growth follows these lines of force, although doctors have long known that bone needs stresses such as weight-bearing exercise for bone health, Prof Teoh said. “In Nikita’s case, we won’t know till five years later whether the bone is hard enough; we hope that it will continue to remodel and in due time it’ll be almost perfect.” Regrown bone has other benefits, he added. When large titanium plates or pieces are used, the patient’s body may reject them, and there is a risk of infection about three to four years later. Dr Goh Bee Tin of the National Dental Centre has used Prof Teoh’s biodegradable plastic scaffolds to repair the jaws of about 20 patients. Currently, patients have their own bone grafted from a hip or leg, but this means extra surgery and pain, Dr Goh said. Other work in bone tissue engineering revolves around improving the biodegradable scaffolds. National University of Singapore doctoral student Wang Zuyong and colleagues from other universities and hospitals here found that stretching a thin plastic film created tiny grooves that aligns stem cells as they develop, helping nerves and vessels to grow true. The plastic film is made of the same polycaprolactone material as the fine-meshed scaffold sheets or pieces, and will also degrade as tissue grows. At the same time, Prof Teoh and his colleagues developed a bioreactor that spins on two axes, rather than the conventional reactors that spin on one axis like a roast on a spit. They found that bone grown using the bioreactor that spins on two axes is stronger and has fewer dead cells, as such bioreactors mimic the mechanical forces present in the body. Now, the two-axis bioreactor technology has been licensed to home-grown start-up QuinXell Technologies. Still, others work at the level of cells. Professor Charles James Kirkpatrick of the Johannes Gutenberg University in Germany, who presented at the congress, studies how bone cells “talk” to their surrounding environment when they are implanted, to encourage blood vessels to grow in and through the bone to feed it with nutrients and oxygen. And at the Agency for Science, Technology and Research’s Institute of Medical Biology, Dr Simon Cool and Dr Victor Nurcombe study how sugars called heparan sulfates control cell growth. Heparan sulfate-treated scaffolds could be used instead of putting large doses of growth factors straight into patients’ bodies, which some studies have shown to carry the risk of tumours. While simply implanting or transplanting bone is relatively straightforward, the challenge facing researchers is to remodel bone and get blood vessels and nerves to regrow accurately, Prof Teoh said.