Bioglass: the story of Larry Hench
Larry Hench revolutionised the field of biomedical materials through his discovery of Bioglass. Now Professor Julian Jones tells the story of the man behind the material.
Bioglass was the first synthetic material found to form a bond with living tissue, changing the way clinicians and medical device companies thought about biomaterials, which have been used to heal the damaged bones of more than one million patients worldwide. Bone can heal itself when there is a small or thin fracture but, when a defect is large, clinicians take bone from other parts of the body to help its repair. The problem is two fold – this damages the donor site, which can get infected, and there is little spare bone available. Before Larry Hench discovered Bioglass, biomaterials were selected for their corrosion resistance, for example, stainless steels or cobalt chrome alloys. The problem is that no material is truly bioinert – everything stimulates a response. In the case of nearly inert materials, they are encapsulated with fibrous tissue and sealed off from the rest of the body. Eventually, the material is pushed out or rejected. Bioglass changed that.
The initial studies
It all started with a bus ride. Larry Hench was a young Faculty member at the University of Florida, USA. He had recently set up his ceramics research group, working on radioactivity-resistant conductive ceramics, having obtained his PhD and undergraduate degree from Ohio State University. On the bus to a conference dinner, Larry sat next to a military officer, who he thought might hold some of the US Army research budget – he seized the opportunity talk to the officer about his research.
At the European Society for Biomaterials meeting in 2014, after receiving the prestigious Acta Biomaterialia Gold Medal, Professor Hench recounted how that chance meeting changed his life as well as the field of biomaterials and medicine. It wasn't that the officer liked Hench's research – quite the opposite. The officer told him that he had returned from Vietnam, where he had seen horrific field injuries. He said that medical teams were able to save lives but not limbs. He challenged Hench – if he could develop materials that could withstand extreme environments, couldn’t he make materials that could withstand the aggressive environment of the body? Hench returned to his laboratory and began reading biology and medical text books, to understand what bone was, which lead him to design a glass composition that would release calcium ions as it dissolved.
Earlier studies in 1969 led Hench to give samples of a promising glass composition to a clinical colleague to carry out the first animal tests. The surgeon called him, saying that he had a problem with the samples. Hench told him he would get back to the drawing board and design a new composition, but the surgeon said, "No, you don’t understand, I can’t get them out of the bone defect." He explained that the materials were stuck fast on the bone, something that had never been seen before. Even now, the first composition, termed 45S5 and containing 45wt% silica (window glass has upwards of 70wt% silica), has not been bettered in terms of stimulating a beneficial bioactive response in bone defects.
A novel innovation
The first Bioglass device was used in patients in 1984, when Hench teamed up with Ellis Douek, a leading clinician at Guy’s Hospital, London. A profoundly deaf patient, who had lost his hearing from an infection that caused degradation of the bones of her middle ear, was able to hear again. The Bioglass implant, later known as Douek-MED, replaced the bones and transmitted sound from the eardrum to the inner ear. The second commercial device arrived in 1988, an Endosseous Ridge Maintenance Implant (ERMI), which were cones of Bioglass that could be inserted into tooth extraction sites to restore tooth roots, providing stable platforms for dentures.
Monolithic Bioglass implants are no longer in widespread clinical use, as surgeons prefer to be able to mould granular materials or putties during surgery. In 2004, Hench’s former student, Dr Ian Thompson, co-founded OSspray Ltd and developed the product Sylc, which can be used by dental healthcare professionals as a Bioglass spray to clean and mineralise exposed dentine. The most commercially successful use of Bioglass, is the toothpaste ingredient NovaMin, a fine particulate using the same Bioglass composition. It has been proved to provoke mineralisation of dentine, which seals the tubules. Sensodyne Repair and Protect, which contains NovaMin, is now available in more than 20 countries (see also The search for a new amalgam).
Bioglass has improved the lives of many patients worldwide and Larry Hench’s contribution has been recognised by many prestigious international awards, such as the MRS Von Hippel in 1998, and the IOM3 Chapman Award in 2004. His review Bioglass: from concept to clinic, is the most cited paper in the history of the American Ceramic Society journal, with around 3,000 citations to date.
Preclinical studies often directly compared the performance of Bioglass particulates with that of other bioactive ceramics and Bioglass usually outperformed its competitors, such as synthetic hydroxyapatite, in terms of speed and quality of bone regeneration. The reason for this was only discovered in 2000, following Hench's move to Imperial College London, UK, when he teamed up with Professor Dame Julia Polak. With the help of their PhD student Ioannis Xynos and Dr Lee Buttery, they found that the dissolution productions of the glasses, soluble silica and calcium ions, provided the signals to bone cells tell them to produce more bone. This enabled them to obtain approval for using the claim ‘osteostimulation’ for the product NovaBone. Clinicians could now relate to the concept of biomaterials guiding bone regeneration, rather than replacing the tissue.
Orthopaedic surgeons would like a Bioglass device that can act as a 3D template for bone regeneration by mimicking the structure of porous bone, with pore channels wide enough for cells, blood vessels and new bone tissue to grow. The original Bioglass composition cannot be made porous while maintaining its glassy amorphous structure, because the 45S5 composition crystallises during sintering. The sol-gel foaming process was developed in Hench’s laboratory, by Dr Pilar Sepulveda and myself, to overcome this problem. Sol-gel glass networks assemble at room temperature and a foaming step can be introduced to produce the pore network. Strengths matched porous bone while providing a bioactive and biodegradable template. Bioactive glass scaffolds can now be 3D printed, allowing specific pore architectures to be built.
Not just biomaterials and bone
In addition to Bioglass and sol-gel bioactive glasses, Hench contributed to related fields, such as ceramics, glass-ceramics – glass corrosion, nuclear waste immobilisation – nanotherapeutics (nanoceria), optical glasses and batteries. His work on cellular responses to biomaterials led him to work with Dr Ioan Notingher on the use of Raman spectroscopy to monitor the behaviour of live cells non-invasively, in a technique they named NovaTest.
Hench retired from Imperial College London in 2005, moving back to Florida, USA, to pursue other interests, including the founding of a new Biomedical Engineering undergraduate programme at Florida Institute of Technology and filming a distance learning course in partnership with the American Ceramic Society. During the last decade, a host of materials have been developed that have their heritage in Bioglass. Researchers have found that the delivery of other ions from glasses have other therapeutic benefits, such as strontium for osteoporosis, lithium for osteoarthritis and cobalt for wound healing. Softer, more flexible hybrid biomaterials, are less brittle than Bioglass but maintain many of its benefits.
Hench, who died in December 2015 continues to support R&D posthumously, leaving funds to encourage study, and a series of science-themed children’s fiction books he authored to pass his passion on to the next generation.
Larry Hench (1938-2015) was University Professor of Biomedical Engineering in the Florida Institute of Technology and Professor Emeritus at Imperial College, London, UK and University of Florida, USA. He was elected to the US National Academy of Engineering and the World Academy of Ceramics and was a Distinguished Life Member of the American Ceramic Society.
Professor Julian Jones FIMMM is a Professor of Biomaterials at Imperial College London and a Fellow of The American Ceramics Society. His research interests include biomaterials for regenerative medicine. In 2004, he was awarded the Silver Medal by IOM3 for Outstanding Achievement in Materials Science.