Jan Hall

Publications of Jan Hall

• Evaluation of implants coated with recombinant human bone morphogenetic protein-2 and vacuum-dried using the critical-size supraalveolar peri-implant defect model in dogs.

  Authors: John F Decker, Jaebum Lee, Carlo Alberto Cortella, Giuseppe Polimeni, Michael D Rohrer, John M Wozney, Jan Hall, Cristiano Susin, Ulf M E Wikesjö

  Journal of periodontology. 12/2010; 81(12):1839-49.

  Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling.Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling. Twelve male adult Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load, six animals), or by immersion of the entire implant in a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation. Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P >0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P >0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P <0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P <0.05). Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

• Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations.

  Authors: Giuseppe Polimeni, Ulf M E Wikesjö, Cristiano Susin, Mohammed Qahash, Richard H Shanaman, Hari S Prasad, Michael D Rohrer, Jan Hall

  Journal of clinical periodontology. 08/2010; 37(8):759-68.

  In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinantIn vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 microg rhGDF-5, and six animals received implants coated with 120 microg rhGDF-5 or left uncoated (control). Treatments were alternated between jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7, and 8 post-surgery when they were euthanized for histologic evaluation. The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (+/-SD) 1.6+/-0.6 mm for implants coated with 120 microg rhGDF-5 versus 1.2+/-0.5, 1.2+/-0.6, and 0.6+/-0.2 mm for implants coated with 60 microg rhGDF-5, 30 microg rhGDF-5, or left uncoated, respectively (p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3-4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 microg dose exhibiting more advanced remodelling than the 60 and 30 microg doses. All treatment groups exhibited clinically relevant osseointegration. rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects.

• Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs.

  Authors: Jaebum Lee, John F Decker, Giuseppe Polimeni, Carlo Alberto Cortella, Michael D Rohrer, John M Wozney, Jan Hall, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 03/2010; 37(6):582-90.

  Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partiallyImplants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Materials and Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05). Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

• Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations.

  Authors: Cristiano Susin, Mohammed Qahash, Giuseppe Polimeni, Ping Hung Lu, Hari S Prasad, Michael D Rohrer, Jan Hall, Ulf M E Wikesjö

  Journal of clinical periodontology. 03/2010; 37(6):574-81.

  Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bonePre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1+/-1.0 versus 3.6+/-1.7 mm and 3.6+/-1.9 versus 3.1+/-1.8 mm(2); and bone density 56%versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone-implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects.

• Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observations.

  Authors: Ulf M E Wikesjö, Mohammed Qahash, Giuseppe Polimeni, Cristiano Susin, Richard H Shanaman, Michael D Rohrer, John M Wozney, Jan Hall

  Journal of clinical periodontology. 11/2008; 35(11):1001-10.

  BACKGROUND: Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. TheBACKGROUND: Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. MATERIAL AND METHODS: Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation. RESULTS: Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (+/-SD) 4.4+/-0.4, 4.2+/-0.7 and 4.2+/-1.2 versus 0.8+/-0.3 mm; and 5.0+/-2.2, 5.6+/-2.2 and 7.4+/-3.5 versus 0.7+/-0.3 mm(2), respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration. CONCLUSIONS: rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects.

• Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior mandible (Type II bone) in dogs.

  Authors: Ulf M E Wikesjö, Andreas V Xiropaidis, Mohammed Qahash, Won Hee Lim, Rachel G Sorensen, Michael D Rohrer, John M Wozney, Jan Hall

  Journal of clinical periodontology. 11/2008; 35(11):985-91.

  BACKGROUND: Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was toBACKGROUND: Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was to determine if adsorbing recombinant human bone morphogenetic protein-2 (rhBMP-2) onto a titanium porous oxide (TPO) implant surface might enhance or accelerate local bone formation and support osseointegration in a large animal oral/maxillofacial orthotopic model. MATERIAL AND METHODS: Endosseous implants with a TPO surface were installed into the edentulated posterior mandible in eight adult Hound Labrador mongrel dogs. The implant surface had been adsorbed with rhBMP-2 at 0.2 or 4.0 mg/ml. TPO implants without rhBMP-2 served as control. Treatments were randomized between jaw quadrants. Mucosal flaps were advanced and sutured leaving the implants submerged. Clinical and radiographic evaluations were made immediately post-surgery, at day 10 (suture removal), and week 4 and 8 post-surgery. The animals received fluorescent bone markers at week 3, 4, and at week 8 post-surgery, when they were euthanized for histologic analysis. RESULTS: TPO implants coated with rhBMP-2 exhibited dose-dependent bone remodelling including immediate resorption and formation of implant adjacent bone, and early establishment of clinically relevant osseointegration. The resulting bone-implant contact, although clinically respectable, appeared significantly lower for rhBMP-2-coated implants compared with the control [rhBMP-2 (0.2 mg/ml) 43.3+/-10.8%versus 71.7+/-7.8%, p<0.02; rhBMP-2 (4.0 mg/ml) 35.4+/-10.6%versus 68.2+/-11.0%, p<0.03]. CONCLUSIONS: rhBMP-2 adsorbed onto TPO implant surfaces initiates dose-dependent peri-implant bone re-modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.

• Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates.

  Authors: Ulf M E Wikesjö, Yi-Hao Huang, Andreas V Xiropaidis, Rachel G Sorensen, Michael D Rohrer, Hari S Prasad, John M Wozney, Jan Hall

  Journal of clinical periodontology. 11/2008; 35(11):992-1000.

  BACKGROUND: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogeneticBACKGROUND: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. MATERIAL AND METHODS: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. RESULTS: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone-implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone-implant contact ( approximately 75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. CONCLUSION: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval.

• Histological and biomechanical evaluation of phosphorylcholine-coated titanium implants.

  Authors: Cristiano Susin, Mohammed Qahash, Jan Hall, Lars Sennerby, Ulf M E Wikesjö

  Journal of clinical periodontology. 03/2008; 35(3):270-5.

  OBJECTIVE: Compounds considered for drug delivery from oral implant surfaces in support of local bone formation might themselves influence osseointegration. Phosphorylcholine (PC) polymers have beenOBJECTIVE: Compounds considered for drug delivery from oral implant surfaces in support of local bone formation might themselves influence osseointegration. Phosphorylcholine (PC) polymers have been shown to enhance the biocompatibility of medical devices and to serve as drug delivery systems. The objective of this study was to evaluate local bone formation and osseointegration at PC and positively charged PC (PC+)-coated endosseous implants in an established rabbit model. MATERIAL AND METHODS: Sixteen adult female New Zealand White rabbits were used. Eight animals received PC-coated and control titanium porous oxide surface implants placed in the left and right distal femural condyle (trabecular bone) and proximal tibial metaphysis (cortical bone) using aseptic routines. The remaining eight animals similarly received PC+ and control implants. One implant was placed in each femural condyle and two implants in each tibial metaphysis. Experimental and control implants were alternated between the left and right hind legs. Fascia and skin were closed in layers. The animals were euthanized following a 6-week healing interval for biomechanical (removal torque) and histometric analyses. RESULTS: Peri-implant bone density was considerably greater at tibial compared with femoral sites within as well as immediately outside the implant threads. However, there were no significant differences in bone density among PC, PC+, and control implants. Nevertheless, bone-implant contact was significantly lower at PC compared with PC+ and control implants in cortical bone (p<0.05). Numerical differences in trabecular bone did not reach statistical significance. The removal torque evaluation revealed significantly lower values for PC compared with PC+ and control sites (p<0.05). CONCLUSION: The histometric and biomechanical analyses suggest that PC coating may influence biological processes and ultimately osseointegration of endosseous implants. Apparently, incorporation of cationic charges may reverse or compensate for this scenario. Nevertheless, both PC coatings exhibited clinically acceptable osseointegration. In perspective, PC technology appears to be a viable candidate delivery system for agents in support of local bone formation at endosseous implant surfaces.

• Bone healing dynamics at buccal peri-implant sites.

  Authors: Mohammed Qahash, Cristiano Susin, Giuseppe Polimeni, Jan Hall, Ulf M E Wikesjö

  Clinical oral implants research. 02/2008; 19(2):166-72.

  BACKGROUND: It is common belief that immediate implant placement into extraction sites may act to preserve the alveolar process. The objective of this study was to evaluate healing dynamics at buccalBACKGROUND: It is common belief that immediate implant placement into extraction sites may act to preserve the alveolar process. The objective of this study was to evaluate healing dynamics at buccal peri-implant sites in relation to the dimensions of the alveolar ridge. METHODS: Bilateral, critical-size, supraalveolar, peri-implant defects were created in 12 male Hound Labrador mongrel dogs following surgical horizontal cut-down of the alveolar ridge. Each jaw quadrant received three 10-mm titanium implants placed 5 mm into extraction sites of the third and fourth premolar teeth leaving 5 mm in a supraalveolar position. The mucoperiosteal flaps were advanced, adapted, and sutured for primary intention healing. Bone fluorescent markers were administered at weeks 3 and 4 postsurgery, and pre-euthanasia. Incandescent, polarized, and fluorescent light microscopies were used to assess the width of the buccal wall of the alveolar ridge and local bone remodeling over the 8-week healing interval. RESULTS: There was a significant association between the width of the buccal alveolar ridge and extent of bone resorption evaluated by incandescent and fluorescent light microscopy. A non-linear association was observed between the buccal ridge width and resorption of the alveolar ridge. A 2-mm threshold was established to account for this non-linearity. The strength of this association was two times greater in specimens with a buccal ridge width <2 mm compared with a wider ridge (beta=1.62 vs. 0.80) observed by fluorescent light microscopy. Accordingly, mean buccal resorption was significantly greater when the ridge width was <2 mm. Fluorescent light microscopy consistently showed greater buccal resorption compared with incandescent light microscopy (P<0.05). Agreement between the examination techniques was low (concordance correlation coefficient=0.49), especially for higher values of buccal resorption. CONCLUSION: When implants are placed into extraction sites, proximity to the buccal alveolar crest appears a major consideration. The observations herein suggest that the width of the buccal alveolar ridge should be at least 2 mm to maintain the alveolar bone level. These observations likely have general implications for implant placement using most surgical protocols.

• Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model.

  Authors: Jan Hall, Rachel G Sorensen, John M Wozney, Ulf M E Wikesjö

  Journal of clinical periodontology. 06/2007; 34(5):444-51.

  BACKGROUND: The objective of this study was to evaluate local bone formation at titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2).BACKGROUND: The objective of this study was to evaluate local bone formation at titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: In vitro studies were used to estimate the kinetics of I125-labeled rhBMP-2 released from TPO surfaces with narrow (N) or open (O) pores. Machined/turned titanium (MT) surfaces served as control. The rat ectopic model was used to assess local bone formation. Briefly, TPO-N, TPO-O, and MT disc implants adsorbed with 5, 10, or 20 microg rhBMP-2, respectively, were implanted subcutaneously into the ventral thoracic region in 5-week-old male Long Evans rats. The animals were euthanized at day 14 postsurgery when implants with surrounding tissues were removed, radiographed, and gross observations recorded. The specimens were processed for histologic evaluation using conventional cut-and-grind techniques. TPO implants without rhBMP-2 included in a preliminary evaluation revealed no evidence of bone formation, tissue encapsulation, or vascularity, thus such controls were not further used. RESULTS: TPO and MT implant surfaces adsorbed with 5 microg rhBMP-2 retained 2.3-5.4% rhBMP-2 following immersion and rinse in buffer, and 1.1-2.2% rhBMP-2 following repeated immersions and rinses over 27 days. TPO implants retained the most rhBMP-2 and MT implants retained the least. Explants revealed increased hard tissue formation, tissue encapsulation, and vascularity at TPO compared with MT implants. Radiographic observations were consistent with the explant observations. The histologic analysis showed greater amounts of bone formation, osteoblastic cells, osteoid, marrow, tissue encapsulation, vascularity, and bone voids for implants adsorbed with 10 and 20 microg rhBMP-2, and for TPO implants at the 5-microg rhBMP-2 dose. The histometric analysis revealed significantly greater bone formation at TPO-O than at MT implants at the 5-microg rhBMP-2 dose. All surfaces showed significant bone formation at the 10- and 20-microg dose. CONCLUSIONS: rhBMP-2 adsorbed onto TPO implant surfaces executes an osteoinductive effect including bone contacting the implant surface. This effect is surface- and dose-dependent; the TPO-O surface yielding the most bone at the low discriminating rhBMP-2 dose.

• The critical-size supraalveolar peri-implant defect model: characteristics and use.

  Authors: Ulf M E Wikesjö, Cristiano Susin, Mohammed Qahash, Giuseppe Polimeni, Knut N Leknes, Richard H Shanaman, Hari S Prasad, Michael D Rohrer, Jan Hall

  Journal of clinical periodontology. 12/2006; 33(11):846-54.

  OBJECTIVE: Novel implant technologies and reconstructive therapies for alveolar augmentation require pre-clinical evaluation to estimate their biologic potential, efficacy, and safety before clinicalOBJECTIVE: Novel implant technologies and reconstructive therapies for alveolar augmentation require pre-clinical evaluation to estimate their biologic potential, efficacy, and safety before clinical application. The objective of this report is to present characteristics and use of the critical-size, supraalveolar, peri-implant defect model. METHODS: Bilateral extraction of the mandibular premolars was performed in 12 Hound Labrador mongrel dogs following horizontal surgical cut-down of the alveolar ridge approximating 6 mm. Each jaw quadrant received three custom-produced TiUnite, phi 4.0 x 10 mm threaded implants placed into osteotomies prepared into the extraction sites of the third and fourth premolars. The implants exhibited a reference notch 5 mm from the implant platform to facilitate surgical placement leaving 5 mm of the implant in a supraalveolar position, and to serve as a reference point in the radiographic, histologic and histometric analysis. The implants were submerged under the mucoperiosteal flaps for primary intention healing. Fluorescent bone markers were administered at weeks 3 and 4 post-surgery, and pre-euthanasia. The animals were euthanized following an 8-week healing interval when block biopsies were collected for analysis. RESULTS: Healing was generally uneventful. The radiographic and histometric evaluations demonstrate the limited osteogenic potential of this defect model. Whereas lingual peri-implant sites exhibited a mean (+/-SE) bone gain of 0.4+/-0.1 mm, resorption of the buccal crestal plate resulted in a mean bone loss of 0.4+/-0.2 mm for an overall osteogenic potential following sham-surgery averaging 0.0+/-0.1 mm. Overall bone density and bone-implant contact in the contiguous resident bone averaged 79.1+/-1.1% and 76.9+/-2.3%, respectively. CONCLUSION: The results suggest that the critical-size, supraalveolar, peri-implant defect model appears a rigorous tool in the evaluation of candidate technologies for alveolar reconstruction and osseointegration of endosseous oral implants. Limited innate osteogenic potential allows critical evaluation of osteogenic, osteoconductive, or osteoinductive technologies in a challenging clinical setting.

• Bone-implant contact at calcium phosphate-coated and porous titanium oxide (TiUnite)-modified oral implants.

  Authors: Andreas V Xiropaidis, Mohammed Qahash, Won Hee Lim, Richard H Shanaman, Michael D Rohrer, Ulf M E Wikesjö, Jan Hall

  Clinical oral implants research. 11/2005; 16(5):532-9.

  BACKGROUND: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered lessBACKGROUND: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone-implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnite)-modified surface. MATERIAL AND METHODS: Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. RESULTS: There were no remarkable differences in bone formation and apparent bone-implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone-implant contact was 71% and 57% (P=0.027) for TO-modified and CP-coated implants, respectively. CONCLUSIONS: We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important.

• Bone formation at titanium porous oxide (TiUnite) oral implants in type IV bone.

  Authors: Yi-Hao Huang, Andreas V Xiropaidis, Rachel G Sorensen, Jasim M Albandar, Jan Hall, Ulf M E Wikesjö

  Clinical oral implants research. 02/2005; 16(1):105-11.

  BACKGROUND: Several oral implant design advances have been suggested to overcome poor bone quality, an impediment for successful implant treatment. A novel titanium porous oxide (TPO) surface hasBACKGROUND: Several oral implant design advances have been suggested to overcome poor bone quality, an impediment for successful implant treatment. A novel titanium porous oxide (TPO) surface has been shown to offer favorable results in several settings. The objective of this study was to evaluate the local bone formation and osseointegration at TPO-modified implants in type IV bone. METHOD: Three TPO surface-modified implants (TiUnite) were installed into the edentulated posterior maxilla in each of 8 Cynomolgus monkeys. The animals were injected with fluorescent bone labels at 2, 3, 4 and 16 weeks post-surgery and were euthanized at week 16 when block biopsies were collected for histologic analysis. RESULTS: The predominant observation of the TPO implant surface was a thin layer of new bone covering most of the implant threads. Mean (+/-SE) bone-implant contact for the whole study group was 74.1 +/- 4.8%. There was a significant variability in bone-implant contact between animals (P = 0.0003) and between sites of the same animal (P < 0.0001). The variance in bone-implant contact was 30% larger among sites of the same animal than between different animals (187.5 vs. 144.8, respectively). There was a small but significant difference in bone density immediately outside, compared to within the threaded area of the implants (37.1 +/- 3.2% vs. 32.1 +/- 3.2%, P < 0.0001). Bone density outside the implant threads was significantly correlated (beta = 0.682, P < 0.0001) with the bone density within the threaded area. Bone density within the threaded area was significantly correlated (beta = 0.493, P = 0.0002) with bone-implant contact, whereas bone density outside the implant threads did not have a significant effect (beta = 0.232, P = 0.1). CONCLUSIONS: The results suggest that the TPO surface possesses a considerable osteoconductive potential promoting a high level of implant osseointegration in type IV bone in the posterior maxilla.

• Stimulation of directed bone growth at oxidized titanium implants by macroscopic grooves: an in vivo study.

  Authors: Jan Hall, Patricia Miranda Burgos, Lars Sennerby

  Clinical implant dentistry and related research. 02/2005; 7 Suppl 1:S76-82.

  BACKGROUND: The influence of thread design at the millimeter level and surface topography at the micrometer level on bone integration and the stability of dental implants have been studiedBACKGROUND: The influence of thread design at the millimeter level and surface topography at the micrometer level on bone integration and the stability of dental implants have been studied extensively. However, less is known about the influence of implant structures in the range of 50 to 200 microm. PURPOSE: The present in vivo investigation was undertaken to study if bone formation and implant stability were influenced by 110 (S1) and 200 (S3) microm-wide and 70 microm-deep grooves positioned at a thread flank of oxidized titanium implants. MATERIALS AND METHODS: Eighteen rabbits and oxidized titanium implants (3.75 mm in diameter and 7 mm long) were used in the study. Nine rabbits received three control implants and three test implants with a 110 microm-wide groove added to one thread flank. The remaining nine rabbits received three control implants and three test implants with a 200 microm-wide groove. The animals were followed for 6 weeks. Removal torque (RTQ) tests were applied to two of the implants in each leg. The remaining implant per leg was retrieved for histology. The degree of bone fill within the grooves and corresponding bone formation at the opposing surfaces, the bone area within the threads, and the degree of bone-implant contact were calculated for each implant. RESULTS: The histologic analyses revealed an affinity for bone formation within the grooves. The RTQ tests showed that the peak RTQ was approximately 30% higher for the S1 implants compared with control implants without a groove. The difference was statistically significant (p < .05) for tibial and pooled implants. A similar but smaller and not statistically significant effect, approximately 8%, was measured for the S3 implants. The histomorphometric measurements confirmed the observed affinity of bone for the grooves. For S1 implants, 78.7 +/- 15.8% of the grooves were filled with bone, whereas only 46.2 +/- 27% of the corresponding flank surface showed the presence of bone (p < .05). The corresponding figures for S3 and control implants were 72.7 +/- 25.1% and 48.5 +/- 13.6%, respectively (p < .05). The degrees of bone-implant contact and bone area within the threads were similar for test and control implants. CONCLUSION: It is concluded that 110 and 200 microm-wide and 70 microm-deep grooves at oxidized implant surfaces stimulated bone to preferentially form within and along the groove in the rabbit model. The 110 microm-wide groove was shown to increase the resistance to shear forces significantly. It is suggested that implants with such a groove may be one way to optimize implant stability in suboptimal clinical conditions.

• Evaluation of a novel calcium phosphate-coated titanium porous oxide implant surface: a study in rabbits.

  Authors: Nicholas M Poulos, Nancy A Rodriguez, Jaebum Lee, Frederick A Rueggeberg, Peter Schüpbach, Jan Hall, Cristiano Susin, Ulf M E Wikesjö

  The International journal of oral & maxillofacial implants. 26(4):731-8.

  To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. Twenty adult male New Zealand White rabbits were used. Each animal received two titaniumTo evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface. Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically. Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 81.8% ± 2.8% and 75.7% ± 4.6%, respectively, and at 4 weeks the bone-implant contact values were 79.4% ± 2.8% and 73.5% ± 4.2%, respectively; these differences were not significant. Backscatter scanning electron microscopy also showed no significant differences in local bone density at control and test implants at 2 and 4 weeks (range, 55% to 72% within the thread area and 75% to 81% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 66.4% ± 2.9% and 61.5% ± 5.1%, respectively, and at 4 weeks mean values were 60.1% ± 4.2% and 53.3% ± 4.6% (differences not significant). The results suggest that the novel CaP-coated surface effectively supports osseointegration.