Smart Biomaterials, Smarter Medicine?

“End of fillings in sight”was The Telegraph's headline in a recent article reporting the promotion of natural tooth repair from a team at King's College London (UK). The study found thatwhen a biodegradable collagen sponge soaked in the drug tideglusib (a glycogen synthase kinase-3 inhibitor) was implanted into a tooth cavity, it mobilized resident stem cells in the dental pulp to stimulate the production of dentine. As the sponge degraded, it was replaced by reparative dentine until the toothwas completely fixed. Although an exciting development, dentists should not worry...yet. The repaired teeth in this study belonged to mice. Whether or not this process can be used to repair larger holes of the size typically found in humans remains to be seen. However, what this research illustrates is the use of a novel biomaterial that might one day replace the need for metal amalgam or ceramic fillings by coopting the body's natural regenerative process. Usingmaterials to address a biological problem is not a new concept. As with dental fillings, artificial hips, heart stents and orthopedic implants are all examples of non-biological materials being deployed in the human body to fulfil a health requirement. What these materials have in common is that they provide functional or structural support, but remain relatively inert. What if materials could be designed that responded to physical, chemical and/or biological cues? Advances in manufacturing processes combined with cross-talk between scientific and engineering disciplines have resulted in a rapidly emerging area within bioengineering to develop smart biomaterials. Next-generation biomaterials are rationally designed to better serve a desired function by actively or adaptively responding to dynamic stimuli. One of the pioneers of smart biomaterial development is Robert Langer, distinguishedMIT professor and 2016 recipient of the Benjamin Franklin Medal in Life Sciences. His multidisciplinary team has the expertise to tweak the macromolecular characteristics of a material so that it performs in novel and sometimes unexpectedways. One example of this approach is their creation of an alginate hydrogel that mitigates an inflammatory response when applied in vivo. Using a combinatorial approach to chemically modify alginate, a large library of variants was established. Variants with triazole derivatives were shown to inhibit the activation of macrophages in mice and non-human primates. By alleviating the foreign body response, this class of hydrogels was used to encapsulate human stem cell-derived β-cells and, when implanted in vivo, correct long-term glycemic control in diabetic mice. Such a smart material could be applied to a variety of biomedical indications, for example by coating implantable medical devices that often result in fibrosis and device failure. As well as immuno-engineering a desired response, smart biomaterials have been developed that can improve drug delivery (e.g., liposomes, nanomaterials, and polymeric controlled release systems that respond to pH, temperature or light), adapt cell