Bohner, Marc

Hofstetter, Willy

Saulacic, Nikola

Siegrist, Mark

Strunz, Franziska

English

Bern Open Repository and Information System (BORIS)

bUniversity of Turku, Institute of Dentistry- Department of BiomaterialsScience, Turku, FinlandBackground: Bioactive glasses enhance bone implant integration byincreased osteogenesis. Additionally, factors affecting cell migrationcould prove useful during healing, since successful implant integration isdependent on the cells arriving at the implantation site.Purpose: The aim was to assess the migration cues of bioglassesS53P4 and 45S5 to pre-osteoblastic cells (MC3T3-E1) when comparedto more common implant materials hydroxyapatite (HAP) andcarbonate hydroxyapatite (CAP) or alumina (Al2O3) control.Methods: The Boyden chambermigration assaywas used to test thechemotactic attraction ofmaterials towardsMC3T3-E1 cl.4 cells in vitro.After 6, 12, 24, and 48 hours the migrated cells were counted. Theexperiment was repeated in the presence of a calcium sensing receptor(CaSR) blocker (NPS2143) to assess the receptor’s role in migration.Gene expression in response to S53P4, alumina, and 10 mM CaCl2 wasstudied with quantitative PCR.Results: Both bioglasses (S53P4 and 45S5) significantly increasedcell migration compared to control at 12 hours (p=0.01 and p=0.03,respectively), and the positive effect continued after 48 hours. Theinitialmigratory effect of HAP at 24 hours (pb0.001) diminished after 48hours. Alumina had a minor effect on cell migration compared tocontrol. Interestingly, CAP had a negative effect on cell migration. Theblocking of CaSR had no uniform effect. The expression of osteopontinencoding gene Spp1was significantly increased by S53P4 (p=0.05) andCaCl2 (p=0.02) after 24 hours.Conclusions: We found that bioglasses induced a greaterchemotactic effect to pre-osteoblastic cells compared to moreconventional implant materials. Alumina had a minor effect on cellmigration even though it is considered chemically inert. The discoveredmigratory effects are unlikely conveyed through CaSR, but might beindirectly influenced by osteopontin. All these data provide newknowledge of the initial phases of implant integration,which is relevantfor the overall implant ossification.Keywords: Bioglass; Cell migration; Implant; Osteopontindoi:10.1016/j.bonr.2022.101321P020Anabolic effects of rhPTH and novel PTH analog on titaniumosseointegration and bone regeneration in ovariectomized beaglemodelJongbin Leea, Jeongoh Shinb, Sihoon Leec, Jin-Woo KimbaGangneung-wonju National University, Periodontology, Gangneung,Korea- SouthbEwha Womans University, Oral and Maxillofacial Surgery, Seoul,Korea- SouthcGachon University College of Medicine, Internal Medicine and Laboratoryof Genomics and Translational Medicine, Incheon, Korea- SouthIntroduction: Recently, there have been concerns in theosseointegration of titanium dental implants and the integrity ofbone grafts in osteoporotic patients. Little is known for the anaboliceffect of PTH on titanium osseointegration in large ovariectomizedanimals such as beagle.Purpose: To investigate the effect of rhPTH and PTH analog ontitanium osseointegration and bone regeneration.Methods: The beagles received ovariectomy to mimic post-menopausal osteoporosis. After teeth extraction (P1-P4) andtitanium implant, all the animals received three titanium implantsin the right lower jaw. Animals were divided into three groups (n=4for each group): Normal saline injected-control group, injected with40ug/day PTH (Forsteo) group, and 40ug/day PTH analog-injectedgroup. Each animal was injected subcutaneously for 10 weeks andwas sacrificed for evaluation of osseointegration and boneregeneration.Results: The values of bone volume, bone mineral density,trabecular number, thickness, and separation by morphometricanalysis with uCT were highest in the rhPTH-treated group. Eachparameter in the PTH analog-treated group was lower than that inthe rhPTH-treated group but increased than the control group. Basedon Goldner’s trichrome staining for histologic evaluation of boneformation, the bone area was the widest in the rhPTH-treated group,and extensive bone was observed on the titanium implant. Thestaining patterns in the PTH analog and control groups were similarto the uCT results. To determine bone turnover, TRAP staining isperformed, and the number of Trap-positive cells was counted. Themost TRAP-positive cells were detected in the rhPTH-treated group.There is a greater number of TRAP-positive cells in the PTH analog-treated group than control group.Conclusions: The rhPTH and PTH analog can enhanceosseointegrated implants in bone remodeling and increaseosteoanabolic effects. Also, Pharmacological intervention of PTHanalog to osteoporotic patients may provide a way to promoteosseointegration after dental implant placement.doi:10.1016/j.bonr.2022.101322P021Repair of a critical-size defect in estrogen-deficient mice treatedwith bisphosphonatesFranziska Strunza,b, Mark Siegrista, Nikola Saulacica, Marc Bohnerc,Willy HofstetteraaUniversity of Bern, Department for BioMedical Research, Bern,SwitzerlandbUniversity of Bern, Graduate School for Cellular and BiomedicalSciences, Bern, SwitzerlandcRMS Foundation, Bioceramics & Biocompatibility, Bettlach, SwitzerlandBackground/Introduction: Bisphosphonates (BP), a class of anti-resorptive drugs, are the therapy of choice to prevent bone loss inpost-menopausal osteoporosis. Since the inhibition of boneresorption by BP will cause, through coupling, a decrease in boneformation, extended treatment protocols may impair bone healing.Purpose: In this study, β-tri-calcium-phosphate (βTCP) ceramics,coated with the growth factor Bone Morphogenetic Protein-2(BMP2) and an engineered BMP2 analogue (L51P) that inactivatesBMP-antagonists, were inserted into critical-size long bone defects inestrogen-deficient mice to assess bone formation and implantturnover.Methods: Eleven-week-old mice were ovariectomized (OVX) orsham operated. Eight weeks later, bone mass was assessed in allanimals and BP therapy was started. After five weeks, a femoralcritical-size defect was generated, filled with βTCP cylinders loadedwith 0.25μg or 2.5μg BMP2, 2.5μg L51P, 0.25μg BMP2/2.5μg L51P orempty control cylinders and rigidly fixed. Femora were collected 12weeks post-op.Results: Micro-computed-tomography (MicroCT) revealed lowbone formation and osseointegration of implants that were eitherempty or loaded with 2.5μg L51P and 0.25μg BMP2 in sham and OVXmice +/- BP therapy. In contrast, insertion of cylinders loaded with0.25μg BMP2/2.5μg L51P and 2.5μg BMP2 induced bone formationand high biomaterial turnover in sham and OVX animals, this resultwas even more pronounced in BP treated animals. After 12 weeks, nosignificant differences in levels of transcripts encoding bone andcartilage markers were detected by PCR among the experimentalgroups. Relative expression levels of transcripts encoding collagen IAbstracts 7were 150 times higher than those for collagen II and around 5000times higher than those for collagen X.Conclusion(s): MicroCT results demonstrated the potential ofL51P to increase the osteogenic efficiency of BMP2 in the healing ofceramic filled critical size bone defects. The relative expressionprofile of the different collagens suggests intramembranous boneformation in the rigidly fixed defects.doi:10.1016/j.bonr.2022.101323P023Comparison of efficacy of rhBMP2 and rhBMP6 delivered withinautologous blood coagulum with synthetic ceramics in ratsubcutaneous assayNatalia Ivanjkoa, Nikola Stokovica, Marina Milesevica, SlobodanVukicevicaaSchool of Medicine University of Zagreb, Laboratory for MineralizedTissues, Zagreb, CroatiaIntroduction: Majority of bone morphogenetic proteins (BMPs)posess osteoinductive properties, but only rhBMP2 is commercialyavailable for bone regeneration in clinical practice. However, it hasbeen shown that BMP6 is more potent in promoting osteoblasts invitro as compared to the BMP2 and BMP7 due to BMP6 resistance tonoggin inhibition. Osteogrow C is a novel osteogenic deviceconsisting of rhBMP6 in autologous blood coagulum (ABC) withsynthetic calcium phosphate ceramic particles. The aim of this studywas to compare osteogenic potential of rhBMP2 and rhBMP6 in thisnovel device conducting rat subcutaneous assay.Materials and methods: Osteoinductive implants were preparedby mixing rhBMP2 or rhBMP6 in three different doses (5, 20 and 50μg) with 500 μL of blood and 100 mg of synthetic ceramics (500-1700μm, TCP/HA 80/20). Following blood coagulation, osteogenicdevice was implanted subcutaneously in the axillary region ofSprague Dawley rats. Animals were terminated 14 days afterimplantation and implants were analysed by microCT and onhistology sections stained by Goldner stain.Results: MicroCT analyses revealed that rhBMP2 and rhBMP6possess similar osteoinductive potential in low-dose range (5-20 μg,)while rhBMP6 was superior to rhBMP2 when higher dose (50 μg)was applied. Histological analyses demonstrated that all testedformulations induced formation of bone at the surfaces and betweenthe ceramic particles. However, the most extensive amount of bonewas observed on histological sections of implants containing 50 μg ofrhBMP6 confirming the findings of microCT analysis.Discussion: We demonstrated herein that rhBMP6 is superior torhBMP2 when higher BMP doses are used. Higher efficacy of rhBMP6might arise from resistance to noggin inhibition and affinity acrossthe BMP type I receptors in comparison to BMP2 and BMP7.doi:10.1016/j.bonr.2022.101325P024rhBMP6 in autologous blood coagulum with ceramics inducesrapid spinal fusion in sheepNikola Štokovića, Natalia Ivanjkoa, Marko Pecinb, Ana Smajlovicb,Niko Ivkicb, Hrvoje Capakc, Zoran Vrbanacc, Drazen Vnukb, DrazenMaticicb, Slobodan VukicevicaaSchool Of Medicine University Of Zagreb, Laboratory for mineralizedtissues, Zagreb, CroatiabFaculty of Veterinary Medicine University of Zagreb, Clinics for Surgery-Orthopedics and Ophthalmology, Zagreb, CroatiacFaculty of Veterinary Medicine University of Zagreb, Department ofRadiology- Ultrasound Diagnostics and Physical Therapy, Zagreb, CroatiaIntroduction: Osteogrow, an autologous bone graft substitute(ABGS) containing recombinant human Bone Morphogenetic Protein6 (rhBMP6) within autologous blood coagulum (ABC) as a BMPcarrier is a novel therapeutic solution for bone regeneration. Calciumphosphate ceramic particles might be added to Osteogrow toimprove the biomechanical properties of implants.Purpose: This study aimed to evaluate Osteogrow with syntheticceramic particles (Osteogrow C) in the sheep posterolateral spinalfusion (PLF) model.Methods: Osteogrow C implants containing 74-420 μm (n=6) or500-1700 μm (n=6) ceramic particles were prepared as follow:lyophilized rhBMP6 (0,5 mg per implant) was dissolved in water andadded to 8 mL of autologous blood withdrawn from the jugular veinand mixed with ceramic particles. Osteoinductive implants wereplaced between L4-L5 transverse processes of sheep (Ovis Aries,Merinolaandschaf breed, aged 4-5 years). Spinal fusion was assessed9 weeks after surgery by in vivo CT scanning. Animals wereterminated 14 weeks following implantation to further evaluate thespinal fusion outcome by microCT, biomechanical testing, andhistology. The study was approved by the Institutional and NationalEthics CommitteesResults: Osteogrow C implants with both 74-420 and 500-1700μm ceramic particles induced formation of bone and fusion withtransverse processes 9 weeks following implantation as evidenced byin vivo CT scans. Ex vivo microCT, histological and biomechanicalanalyses confirmed these findings and revealed that newly formedbone was completely integrated with native transverse processesproviding biomechanically competent fusion.Conclusions: Osteogrow C implants induce rapid spinal fusion inthe sheep PLF model and provide a possible therapeutic solution forpatients with degenerative disease of the spine.doi:10.1016/j.bonr.2022.101326P029Risk factors for developing sacral insufficiency fracturesJulian Ramin Andresena, Sebastian Radmerb, Reimer Andresenc, AxelProkopd, Guido Schrödere, Hans-Christof SchoberfaSigmund Freud University, Medical School, Vienna, AustriabCentre for Orthopaedics, Specialist practice for orthopedics, Berlin,GermanycWestkuestenklinikum Heide- Academic Teaching Hospital of theUniversities of Kiel- Luebeck and Hamburg, Institute of Diagnostic andInterventional Radiology/Neuroradiology, Heide, GermanydKlinikverbund Suedwest- Sindelfingen- Academic Teaching Hospital ofthe University of Tübingen, Department of Trauma Surgery, Sindelfingen,GermanyeClinic for Surgery- Buetzow, Department of Orthopedics and TraumaSurgery, Buetzow, GermanyfMunicipal Hospital Suedstadt Rostock- Academic Teaching Hospital ofthe University of Rostock, Department of Internal Medicine IV, Rostock,GermanyBackground/Introduction: Fragility fractures of the pelvis havebeen detected with increasing frequency in recent times, wherebytheir incidence will increase further as a result of the increase in lifeexpectancy.Purpose: The objective of the present retrospective investigationon women suffering from sacral insufficiency fractures was todetermine the extent of a possible vitamin-D deficiency and existingosteoporosis.Methods: In 276 female patients aged from 58 - 99 (Ø 81.3) yearswith sacral insufficiency fractures, the fractures were classifiedAbstracts8

Repair of a critical-size defect in estrogen-deficient mice treated with bisphosphonates

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Repair of a critical-size defect in estrogen-deficient mice treated with bisphosphonates

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