Regenerating bone defects using stem cells: experimental and clinical studies
Regenerating bone defects using mesenchymal stem cells: experimental and clinical studies
- Successful treatment and outcome in phase I Clinical trial including 11 patients. - In preclinical models, MSC grown in culture medium supplemented with platelet lysates (PL) or AB serum + FGF2 showed their stemness. - Enhanced degradation on hydrophilic scaffolds than on hydrophobic one in a preclinical study.
Clinical and preclinical studies: The major goal of our observational trial is to develop a durable surgical approach for reconstruction without creating a second bone defect in a donor area. We have evaluated the safety and early efficacy of using a mixture of bone marrow stromal cells (MSC) with biphasic calcium phosphate matrix (BCP) scaffolds to induce functional bone augmentation of sufficient bone volume to install dental implants. Four to 6 months later, augmented alveolar ridges in 11 patients had the volume to facilitate dental implant installation. All 11 patients had uneventful dental implant healing and prosthetic restorations. The patients reported satisfaction with the aesthetic and functional outcomes and no adverse events were observed or reported. The application to prolong the maxillofacial trial and increase the number of patients to 30 has been accepted recently by the Regional Committees for Medical and Health Research Ethics (REK). Another application for an orthopaedic clinical trial (critical sized defects in long bones) has been submitted to REK by Dr. Yngvar Krukhaug, a consultant at the Department of Orthopaedic Surgery, Haukeland University Hospital. Further, a pre-clinical large animal study was designed to test the efficacy of the developed cell/biomaterial construct used in our pilot clinical trial and improve the surgical procedure. This improvement was done by comparing two resorbable membranes as well as comparing the use of pure BCP granules or BCP granules modified with nanodiamond particles. Bone marrow was harvested and MSC were expanded from 6 Göttingen mini pigs. Bilateral alveolar defects were created by extracting 2 premolars and removing buccal bone. MSC were implanted in combination with BCP (7500 cell /mg). The mandibles of 2 out of these minipigs were harvested after 1 and 2 months. The third minipig did not have sufficient MSC to be used. One minipig developed a disc hernia and was euthanized, so mandible samples were harvested at 6 months. The last two pigs were allowed to heal for longer and used for an orthopaedic pre-clinical trial in collaboration with Yngvar Krukhaug. Bone marrow samples were harvested and a critical-sized defect was created in the ulna and stabilized with titanium plates. Currently MSC are being expanded and prepared for implantation in combination with BCP granules. Furthermore, MSC grown in culture medium supplemented with platelet lysates (PL) or AB serum + FGF2 showed their stemness in experimental models. Development of a novel 3D printed resorbable composite scaffolds for large bone defects: It has been demonstrated that copolymer scaffolds of poly(L-lactide) and caprolactone are appropriate candidates for bone tissue engineering. The degradation rates and loss of mechanical integrity were greatly increased in the polymer scaffolds made with hydrophilic co-monomers as shown in our recent report. Further, innovation on fabrication of improved scaffolds for personalized medicine comes from the possibility to combine porous frameworks built through the 3D printing technology to generate specific complex architecture. Scaffolds having tailor-made mechanical and surface properties with enhanced regenerative qualities for cell affinity, and biocompatibility is currently under investigation using the nanotechnology-derived toolbox. This innovation part of the project was presented recently during the Årskonferansen and won the prize for Idea Competition.
A copolymer scaffold functionalized with nanodiamond particles enhances 1 osteogenic metabolic activity and bone regeneration
Accepted in Macromolecular Bioscience
Efficacy of humanized MSC cell cultures for bone tissue engineering: a systematic review with a focus on platelet-derivatives
Submitted to Biomaterials
Cytocompatibility of Wood-derived Cellulose nanofibril Hydrogels with Different Surface Chemistry
Submitted to Biomacromolecules
Stem cells in bone regeneration, a systematic approach and an observational first-in-human trial