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REGENERATING LARGE BONE DEFECTS

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A versatile biomimetic film for coating bone implants

Currently, the gold standard for repairing critical-size bone defects that will not heal by themselves is to use the patient’s own tissue (autograft). Since this process is associated with prolonged pain and high infection risks, European scientists have developed a biomimetic solution that can be adapted to individual patient needs.

Fundamental Research
Health

In the field of orthopaedics and maxillofacial surgery, synthetic bone grafts have emerged as an alternative solution in hip replacement, face or jaw reconstructive surgeries and following curettage of tumours. Apart from mechanical properties, synthetic grafts nowadays demonstrate an osteoconductive capacity: molecules such as growth factors are incorporated in their design to trigger the bone regeneration after surgery. However, the grafts cannot control the delivery of these bioactive molecules, causing inflammation, infection, abnormal bone healing or are structurally insufficient to correct large-size defects.

A biomimetic film with bone-regenerating properties

Ideally, synthetic grafts should be designed to mimic the bone environment in vivo, allowing the spatial and temporal release of bioactive molecules at physiological doses. To address this, the EU-funded REGENERBONE project worked towards innovative medical implants with osteoinductive properties. The project built on technology developed during the EU-funded BIOMIM project consisting of biomimetic films that can be deposited on any material. Built using a layer-by-layer assembly technique, the biomimetic films contain two biopolymers that are widely present in cartilage and bone tissues: hyaluronic acid and a polymer of lysine. In addition, they contain the bone morphogenetic protein 2 (BMP-2) responsible for the activation of bone progenitor cells and their differentiation into bone cells. BMP-2–has already received approval for bone repair in the clinic. “By controlling the conditions for BMP-2 loading in the films, we can precisely control the dose of BMP-2 that we will deliver in vivo,” emphasises principal investigator Catherine Picart. Moreover, the biomimetic films have a nanoscale porosity that endows them with controlled stiffness and enables to fine-tune the release of BMP-2 close to the implant surface. The biomimetic films can be deposited onto practically any implantable material irrespective of chemical composition, geometry, shape and size including ceramics, polymers and metals. “This is a great advantage, as it renders our films suitable for all types of synthetic grafts currently used in bone replacement strategies,” highlights Picart.

Bone-regeneration efficacy

Film-coated implants demonstrated an osteoinductive capacity in vivo when tested in preclinical models. Moreover, scientists used hollow polymeric cylinders coated with the osteoinductive films to repair a bone defect of critical size in rat femurs. The extent of the repair was dependent on the BMP-2 dose and the newly formed tissue resembled the physiology of native bone. REGENERBONE scientists were also able to repair mandibular defects in a large animal model. This type of defect resembles in size those that surgeons have to repair in the clinic. For this purpose, they engineered an innovative implant to fill the bone defect. Coating with the biomimetic film delivered efficient bone repair in a BMP-2-dependent manner without adverse effects.

Future directions

Overall, the promising results have urged REGENERBONE scientists to obtain regulatory approval for testing the biomimetic products in human trials. This will take place in collaboration with the Clinical Investigation Centre for Innovation Technology Network CIC-IT in Bordeaux, specialised in the translation of innovative medical devices. Importantly, the versatility of the technology will enable the construction of tailored implants adapted to the needs of each particular bone defect. The use of biomimetic films extends beyond bone implants and can be employed to coat cell culture microplates for studying cellular signalling and controlling stem cell differentiation. This application was explored under the BIOACTIVECOATINGS project, funded by the EU’s European Research Council, and can be used for drug screening, tissue engineering and toxicology purposes.

Keywords

REGENERBONE, biomimetic, BMP-2, bone defect, synthetic graft, bone implant, osteoinductive, bone regeneration, BIOMIM, BIOACTIVECOATINGS

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