Implant osseointegration in circumferential bone defects treated with latex-derived proteins or autogenous bone in dog's mandible

Background: In sites with diminished bone volume, the osseointegration of dental implants can be compromised. Innovative biomaterials have been developed to aid successful osseointegration outcomes. Purpose: The aim of this study was to evaluate the osteogenic potential of angiogenic latex proteins for improved bone formation and osseointegration of dental implants. Materials and Methods: Ten dogs were submitted to bilateral circumferential defects (5.0×6.3mm) in the mandible. Dental implant (3.3×10.0mm, TiUnite MK3™, Nobel Biocare AB, Göteborg, Sweden) was installed in the center of the defects. The gap was filled either with coagulum (Cg), autogenous bone graft (BG), or latex angiogenic proteins pool (LPP). Five animals were sacrificed after 4 weeks and 12 weeks, respectively. Implant stability was evaluated using resonance frequency analysis (Osstell Mentor™, Osstell AB, Göteborg, Sweden), and bone formation was analyzed by histological and histometric analysis. Results: LPP showed bone regeneration similar to BG and Cg at 4 weeks and 12 weeks, respectively (p≥.05). Bone formation, osseointegration, and implant stability improved significantly from 4 to 12 weeks (p≤.05). Conclusion: Based on methodological limitations of this study, Cg alone delivers higher bone formation in the defect as compared with BG at 12 weeks; compared with Cg and BG, the treatment with LPP exhibits no advantage in terms of osteogenic potential in this experimental model, although overall osseointegration was not affected by the treatments employed in this study. © 2009 Wiley Periodicals, Inc.

Implant Osseointegration in Circumferential Bone Defects Treated with Latex-Derived Proteins or Autogenous Bone in Dog's Mandible

Background: In sites with diminished bone volume, the osseointegration of dental implants can be compromised. Innovative biomaterials have been developed to aid successful osseointegration outcomes. Purpose: The aim of this study was to evaluate the osteogenic potential of angiogenic latex proteins for improved bone formation and osseointegration of dental implants. Materials and Methods: Ten dogs were submitted to bilateral circumferential defects (5.0 x 6.3 mm) in the mandible. Dental implant (3.3 x 10.0 mm, TiUnite MK3 (TM), Nobel Biocare AB, Goteborg, Sweden) was installed in the center of the defects. The gap was filled either with coagulum (Cg), autogenous bone graft (BG), or latex angiogenic proteins pool (LPP). Five animals were sacrificed after 4 weeks and 12 weeks, respectively. Implant stability was evaluated using resonance frequency analysis (Osstell Mentor T, Osstell AB, Goteborg, Sweden), and bone formation was analyzed by histological and histometric analysis. Results: LPP showed bone regeneration similar to BG and Cg at 4 weeks and 12 weeks, respectively (p >= 3.05). Bone formation, osseointegration, and implant stability improved significantly from 4 to 12 weeks (p <= 2.05). Conclusion: Based on methodological limitations of this study, Cg alone delivers higher bone formation in the defect as compared with BG at 12 weeks; compared with Cg and BG, the treatment with LPP exhibits no advantage in terms of osteogenic potential in this experimental model, although overall osseointegration was not affected by the treatments employed in this study.

Effect of Bio-Oss on osseointegration of dental implants surrounded by circumferential bone defects of different dimensions: an experimental study in the dog

OBJECTIVES: This study was designed to evaluate the effect of gap width and graft placement on bone healing around implants placed in simulated extraction sockets of various widths in four Labrador dogs. MATERIALS AND METHODS: Five Osseotite implants per dog were placed in the mandible of four dogs. Two implants were inserted into sites with a 2.37 mm and two with a 1 mm gap present between the implants and bone around the coronal 6 mm of the implants in each dog. For one of each gap sizes, the gap was filled with Bio-Oss, and the other two with blood alone. A fifth implant was inserted without a gap and used as a control. Ground sections were prepared from biopsies taken at 4 months and histometric measurements of osseointegration and bone between the threads made for the coronal 6 mm. RESULTS: The medians for osseointegration ranged from 5.2 mm for control to 1-2.6 mm for the test modalities. There were significant differences for linear measurements of osseointegration (chi(2) 18.27; df 4; P=0.0011) and bone area within threads (chi(2) 23.4; df 4; P=0.0001) between test modalities. CONCLUSIONS: The results suggest that the wider the gap around the implants, the less favourable the histological outcome at short time intervals following treatment. They also infer that bone grafting with an organic bovine bone xenograft seems to lead to a more favourable histological outcome for wider circumferential defects but not for narrower defects.

Comparisons between Bio-Oss® and Straumann® Bone Ceramic in immediate and staged implant placement in dogs mandible bone defects

Objective: To compare immediate and staged approach implant placement in circumferential defects treated with deproteinized bovine bone mineral (DBBM); hidroxyapatite/tricalcium phosphate (HA/TP); autogenous bone (Ab); and coagulum (Cg); upon implant stability, osseointegration and alveolar crest maintenance. Materials and methods: Six dogs underwent extractions of lower premolars, bilaterally. Twelve weeks later four bone defects (6 mm wide/4 mm long) were drilled at one side and randomly filled with DBBM; HA/TP; Ab; and Cg, respectively, and left to heal (staged approach). Eight weeks later one implant (Osseospeed™, AstraTech) was placed in experimental sites. At the same session four defects were drilled on contra-lateral side and implants were inserted immediately after biomaterials grafting (immediate approach). Animals were euthanized 8 weeks later. Implant stability was measured by resonance frequency analysis (RFA) at installation and after sacrifice. Ground sections were prepared for bone contact (BIC); bone area (BA); distance implant shoulder-bone crest (IS-C); distance implant shoulder first bone contact (IS-B); and areas occupied by soft tissue. Results: The BA and BIC were superior in the staged approach. The Cg exhibited higher BIC and BA as compared with other materials at the total implant body (P = 0.004 and 0.012, respectively). The DBBM, HA/TP and Ab groups rendered similar BA and BIC. The immediate approach resulted in less crest resorption compared to staged approach. The biomaterials did not affect the IS-C and IS-B measurements. Particles area tended to be higher in DBBM group than HA/TP (P = 0.15), while soft tissue infiltrate was higher in DBBM group when used in the immediate approach (P = 0.04). The RFA indicated gain in stability in the staged approach (P = 0.002). The correlation test between RFA vs. BIC and BA demonstrated inferior stability for DBBM group in immediate approach (P = 0.01). Conclusions: Implants placed in healed defects resulted in better stability as a consequence of higher BIC and BA. The Cg alone rendered increased BIC compared to other materials in both approaches. Immediate approach should be preferable to staged approach in terms of alveolar crest maintenance. The BIC and BA values did not vary between micro and macro-threads in this experimental model. Implants installed in sites filled with DBBM in immediate approach were less stable. © 2011 John Wiley & Sons A/S.

An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Biomaterial scaffolds in cartilage-subchondral bone defects influencing the repair of autologous articular cartilage transplants

The repair of articular cartilage typically involves the repair of cartilage-subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage-subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite-β-tricalcium phosphate (HA-TCP), poly lactic-glycolic acid (PLGA)-HA-TCP dual-layered composite scaffolds (PLGA/HA-TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After three months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration and histological responses. The results showed that the transplanted cartilage layer supported by HA-TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA-TCP scaffolds. Furthermore, HA-TCP supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan (GAG) contents than that supported by PLGA/HA-TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects.

Tissue engineering bone - reconstruction of critical sized segmental bone defects in a large animal model

Currently, well established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, their application, however, is associated with disadvantages. These include limited access and availability, donor site morbidity and haemorrhage, increased risk of infection, and insufficient transplant integration. As a result, recent research focuses on the development of complementary therapeutic concepts. The field of tissue engineering has emerged as an important alternative approach to bone regeneration. Tissue engineering unites aspects of cellular biology, biomechanical engineering, biomaterial sciences and trauma and orthopaedic surgery. To obtain approval by regulatory bodies for these novel therapeutic concepts the level of therapeutic benefit must be demonstrated rigorously in well characterized, clinically relevant animal models. Therefore, in this PhD project, a reproducible and clinically relevant, ovine, critically sized, high load bearing, tibial defect model was established and characterized as a prerequisite to assess the regenerative potential of a novel treatment concept in vivo involving a medical grade polycaprolactone and tricalciumphosphate based composite scaffold and recombinant human bone morphogenetic proteins.

Bone tissue engineering : reconstruction of critical sized segmental bone defects in the ovine tibia

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds. Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical-sized segmental tibial bone defects in aged sheep

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

Quantitative and qualitative assessment of the regenerative potential of osteoblasts versus bone marrow derived mesenchymal stem cells in the reconstruction of critical sized segmental tibial bone defects in a large animal model

This thesis is about the use of different cells for bone tissue engineering. The cells were used in combination with a novel biomaterial in a large tibial bone defects in a sheep model. Furthermore this study developed a novel cell delivery procedure for bone tissue engineering. This novel procedure of cell delivery could overcome the current problems of cell-based tissue engineering and serve as a baseline for the translation of novel concepts into clinical application.

A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects

SUMMARY: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontium-containing scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. INTRODUCTION: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass (MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. METHODS: In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontium-incorporated mesopore-bioglass (Sr-MBG) scaffolds. RESULTS: The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving Sr-MBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrate-resistant acid phosphatase-positive cells when compared to other modalities. CONCLUSION: The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials.

Implants of polyanionic collagen matrix in bone defects of ovariectomized rats

In recent years, there has been a great interest in the development of biomaterials that could be used in the repair of bone defects. Collagen matrix (CM) has the advantage that it can be modified chemically to improve its mechanical properties. The aim of the present study was to evaluate the effect of three-dimensional membranes of native or anionic (submitted to alkaline treatment for 48 or 96 h) collagen matrix on the consolidation of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats subjected to hormone replacement therapy. The animals received the implants 4 months after ovariectomy and were sacrificed 8 weeks after implantation of the membranes into 4-mm wide bone defects created in the distal third of the femur with a surgical bur. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas, suggesting that the material was biocompatible. Microscopic analysis showed a lower amount of bone ingrowth in the areas receiving the native membrane compared to the bone defects filled with the anionic membranes. In ovariectomized animals receiving anionic membranes, a delay in bone regeneration was observed mainly in animals not subjected to hormone replacement therapy. We conclude that anionic membranes treated with alkaline solution for 48 and 96 h presented better results in terms of bone ingrowth.