Translational approaches for bone construct
Short-term preclinical research should focus on cell growth, cell carriers, scaffolds and other biomaterials, growth factors that enhances bone growth in experimental settings, development 3D printable osteogenic or osteoconductive constructs, or assessing relevant bio-physiological aspects for cell maintenance in bio material, e.g. vascular components, stem cell properties,mechanics, magnets/ easy electricity, and bioreactors. The results should be applicable for clinical studies.
The mid-term aim is to start bone defect repair studies using bone substitute biomaterials in non-malignant diseases (non-irradiated tissues). Targets are mandibular defect repair using bone regeneration technology with scaffolds and/ or CAD – CAM reconstruction (plates and scaffolds).
The research topic needs to be either translational (nonclinical / preclinical) or clinical.The long-term goal is the intra operative reconstruction of facial bone defect using 3D printable bone substitute material. It includes areas like cell preparation techniques, intra operative reconstruction methods, TERM, custom-made scaffold printing and customized (tissue engineered) free flaps
The use of bone tissue engineering for facial bone defect repair with regards to the clinical outcome of orthopedic, oral and maxillofacial procedures is not well established. Despite clear development of CAD-CAM technology in medicine and regenerative medicine in surgery, modern facial reconstructive surgery will not be possible without focused high quality, multispecialty research both on a translational and clinical level.
- What are optimal materials and/or bone substitute materials for additive manufacturing (CAD—CAM) for scaffolds, matrices and implants?
- What are the critical stages in CAD-CAM process in medicine?
- Are cells necessary in implantable bone substitute material?
- What are the relevant stages in bone defect repair and direct (digital) manufacturing technologies in clinical settings?
Open call for proposals
1st Consortium call on the subject: ’Translational approaches for bone constructs: their impact on facial bone reconstruction'
AO CMF Funded Research Projects
Have a look at the latest funded projects under the Translational approaches for bone construct research topic
Project title: Reconstructing a rat mandibular segmental defect with BMP-6, VEGF, and SAG tethered to a polysaccharide scaffoldThe contemporary mainstays for repair of craniofacial (CF) bony defects after trauma, osteonecrosis, and oncologic surgery are fixation, bone grafting and free tissue transfer. These work well in simple defects but are associated with morbidity and higher failure rates when used in complex reconstruction. Further, patients with medical comorbidities and elderly patients are often not eligible for these large procedures. Developing an osteogenic biosynthetic implant for CF reconstruction could alter standards of care in trauma management, osteonecrosis treatment, and oncologic surgical defects.FDA-approved rhBMP-2 is used to treat complex long bone fractures with good results and is frequently used in spinal fusion. Recent work, though, demonstrates this product provides little or no benefit compared with autologous tissue. Furthermore, rhBMP-2 has limited indications in CF reconstruction and is associated with poor outcomes when used off-label. While rhBMP-2 is the primary growth factor used clinically to support osteoinduction, PLGA scaffolds are the most common scaffolds used to support osteoconduction. However, concerns over inflammation secondary to PLGA’s acidic breakdown products have elucidated a need for natural polymer osteoconductive scaffolds. Our preliminary data shows that delivery of VEGF, BMP-6 and smoothened agonist (SAG) tethered to a novel polysaccharide scaffold (PS) significantly enhances bone regeneration in a critical-sized circular rat mandible defect in comparison with BMP-2 tethered to PS (PSBMP2). This PS scaffold developed in our laboratory not only overcomes the shortcomings of PLGA but also provides superior mechanical strength. We now want to investigate the bone regeneration potential of this novel treatment strategy using a clinically-relevant, critical-sized segmental rat mandibular defect model and compare its efficiency with Infuse bone graft (Medtronic), the only FDA-approved product available for CF bone regeneration.
Our central hypothesis is that treatment with PSVEGF+BMP6+SAG is superior to Infuse bone graft with regard to CF bone regeneration. To test this we will create 5 mm critical-sized segmental defects in rat mandibles and treat them with: rigid fixation only; fixation with Infuse bone graft; fixation with nude PS scaffold; fixation with PSSAG; fixation with PSBMP6+SAG; and fixation with PSBMP6+VEGF+SAG. We will assess bony regeneration using radiography, micro-CT, histology and mechanical strength testing.