Bovine bone grafts (BBX) require protein removal as part of the manufacturing process to reduce antigenicity and, in consequence, to be safely used in humans. Deproteinisation may have direct effects on the characteristics of the bone material and on in vivo material performance. This research aimed to comprehensively study the physicochemical and mechanical properties of BBX processed at low deproteinisation processing temperatures. Cubes of bovine bone (8 mm3) were treated with temperatures between 100 °C and 220 °C at 30 °C intervals and with pressures ranging from 1.01 to 24.58 Bar. The samples were characterised topographically and mechanically using scanning electron microscopy (SEM), atomic force microscopy (AFM), and uniaxial bending tests. The organic content and the chemical composition were determined using thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR). X-ray diffraction (XRD) and FTIR were also used to quantitatively determine the specimen crystallinity. Increasing temperature/pressure was associated with decreasing protein levels and compressive strength and increasing surface irregularities and crystallinity. The findings suggest that low-temperature processed bone is likely to exhibit a rapid in vivo degradation rate. The deproteinisation temperature can be adjusted to tailor the graft properties for specific applications.

Calcium phosphate (CP) materials have been used extensively for bone replacement and augmentation due to their similarity to the mineral component of bone. In addition to being non-toxic, they are biocompatible, not recognized as foreign materials in vivo, and most importantly, exhibit osteoconductive behavior, being able to help in bone formation during healing. CPs form an intimate physicochemical bond with the host tissue, termed osseointegration. However the main limitation of calcium phosphates is their inherent brittle nature and poor mechanical performance under complex stress states. As a result, these materials have been used clinically only in non-load-bearing applications, primarily as granules. The primary goal of this research was to enhance mechanical performance of CPs, tricalcium phosphate (TCP) and hydroxyapatite (HAp) to be precise, in an attempt to develop controlled strength-loss resorbable/ bioactive ceramic bone-grafts for hard tissue engineering. In my work on TCP, I selected and introduced small quantities of single and multi-oxide sintering additives in TCP, to study their influence on sintering behavior, densification, mechanical properties and biodegradation/ biomechanical properties in vitro. Through this research, I could improve mechanical performance of [Beta]-tricalcium phosphate ([beta]-TCP) and controlled its rate of biodegradation by introducing of certain additives. In my second work, I improved mechanical performance of HAp (Ca10(PO4)6(OH)2 by reducing particle-size of the powder through the synthesis of stoichiometric, nanocrystalline, single phase HAp powder in the range of 2-20 nm. Synthesis of powder was accomplished via a modified low temperature sol-gel technique using ethanol/ water as solvent.

No description available.

Submitted by Verônica Esteves (vevenesteves@gmail.com) on 2017-09-28T19:33:45Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Flávio Gasperini.pdf: 2318649 bytes, checksum: af9486980e507779dbd5975709e84b4d (MD5) / Approved for entry into archive by Verônica Esteves (vevenesteves@gmail.com) on 2017-09-28T19:34:10Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Flávio Gasperini.pdf: 2318649 bytes, checksum: af9486980e507779dbd5975709e84b4d (MD5) / Made available in DSpace on 2017-09-28T19:34:10Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Flávio Gasperini.pdf: 2318649 bytes, checksum: af9486980e507779dbd5975709e84b4d (MD5) Previous issue date: 2010 / Consultório / Os defeitos críticos ósseos oriundos de trauma, tumores ou doenças degenerativas determinam um desafio no campo da Ortopedia, visto que a reconstrução cirúrgica se faz necessária através de enxertos ósseos. Apesar de os enxertos autógenos serem considerados um “padrão ouro”, as cerâmicas sintéticas a base de Hidroxiapatita (HA) são materiais muito promissores, devido às suas inerentes características biocompatíveis. A possibilidade de diminuição do tamanho das partículas em escala nanométrica e o advento da hidroxiapatita nanoestruturada podem melhorar a remodelação óssea. O objetivo deste estudo foi avaliar a resposta tecidual e a biocompatibilidade de esferas de HA produzidas a partir de partículas nanométricas em comparação às esferas de HA produzidas a partir de partículas micrométricas, ambas no estado sinterizado e não-sinterizado (Sem tratamento térmico), bem como seu potencial de degradação e osteogênese, em relação ao grupo controle (coágulo). Os biomateriais foram implantados em defeitos ósseos nas tíbias de 12 coelhos da raça Nova Zelândia (Oryctolagus cuniculus), pesando entre 2000g e 3500g. As esferas (425-600 μm) tiveram as propriedades físicas e químicas caracterizadas por DRX, FT-IR, MEV e foram também submetidas ao teste de dissolução. Os animais foram divididos randomicamente em cinco grupos: Grupo 1 (Controle) – coágulo sanguíneo; Grupo 2 – HA Sinterizada; Grupo 3 – HA Sem tratamento térmico; Grupo 4 – NanoHA Sinterizada; e Grupo 5 – Sem tratamento térmico. Os animais foram mortos 7 e 28 dias após a cirurgia e as amostras submetidas ao processamento histológico. As esferas não-tratadas eram menos cristalinas que as sinterizadas (DRX e FT-IR), sendo mais solúveis in vitro (teste de dissolução). In vivo, a nanoHA e a HA, ambas sem tratamento térmico, dissolveram e promoveram maior formação de tecido ósseo em relação às esferas sinterizadas. Concluiu-se que os materiais se mostraram biocompatíveis e osteocondutores, porém a neoformação óssea foi mais acentuada nos grupos da HA e nanoHA não-tratadas termicamente. / Bone critical defects from trauma, tumors or degenerative diseases prescribe a challenge in orthopedics, since surgical reconstruction is required by bone grafts. Although autografts are considered a gold standard, the synthetic ceramics based on hydroxyapatite (HA) are promising materials due to their inherent characteristics biocompatible. The possibility of decreasing the size of the particles at the nanometer scale and the advent of nanostructured hydroxyapatite may improve bone remodeling. The aim of this study was to evaluate the tissue response and biocompatibility of HA spheres shape made from nano-sized particles compared to the HA spheres made from micro-sized particles, both in sintered and non-heat treated as well as its potential for degradation and osteogenesis compared to control group (clot). The spheres (425-600 μm) had the physical and chemical properties characterized by XRD, FT-IR, SEM and were also subjected to dissolution test and the biomaterials were implanted in bone defects on 12 New Zealand rabbit’s tibiae (Oryctolagus cuniculus), weighing between 2000g and 3500g. The animals were randomly divided into five groups: Group 1 (Control) - blood clot, Group 2 - sintered HA, Group 3 - non-heat treated HA, Group 4 - sintered NanoHA and Group 5 - non-heat treated NanoHA. Animals were euthanized at 7 and 28 days after surgery and samples submitted to histological procedings. The non-heat treated had a lower cristallinity that the sintered materials (XRD and FT-IR), being more soluble in vitro (dissolution tests). In vivo, NanoHA and HA, both non-treated, degraded and promoted greater bone formation in relation to the sintered spheres. In conclusion, materials showed biocompatibility and osteoconduction, but the bone formation was more accentuated in the non-heat treated groups.

Vários estudos têm abordado fatores que governam a longevidade dos enxertos ósseos \"onlay\". Entretanto, poucas informações têm sido disponibilizadas sobre eventos moleculares que ocorrem ao longo do tempo. Os enxertos de calota craniana têm sido reportados produzir respostas superiores em relação a outras regiões doadoras nas reconstruções maxilo-faciais, mas sem a devida comprovação científica. Este estudo tem por objetivos (1) estudar o padrão morfológico de enxertos ósseos \"onlay\" de calota craniana e compará-los com os eventos biológicos através de respostas imunoistoquímicas e (2) estabelecer os efeitos das perfurações no leito receptor sobre a manutenção do volume e densidade óssea. Sessenta coelhos do tipo New-Zealand White foram submetidos à enxertia óssea \"onlay\" de calota craniana na mandíbula. Em trinta coelhos o leito receptor foi perfurado (grupo perfurado) enquanto nos demais o leito foi mantido intacto (grupo não perfurado). Seis animais de cada grupo foram sacrificados aos 5, 7, 10, 20 e 60 dias após a cirurgia. Cortes histológicos foram preparados da região enxertada para análises imunoistoquímica e histológica. Na avaliação imunoistoquímica se observou marcações das proteínas Osteoprotegerina (OPG), \"Receptor Activator of Nuclear Factor-ß ligand\" (RANKL), Fosfatase Alcalina (ALP), Osteopontina (OPN), \"Vascular Endothelial Growth Factor\" (VEGF), \"Tartrate-Resistant Acid Phosphatase\" (TRAP), Colágeno do tipo I (COL I) e Osteocalcina (OC). O exame tomográfico foi realizado após a cirurgia e no sacrifício dos animais. Os achados histológicos revelaram que as perfurações contribuíram para uma maior deposição óssea nos períodos iniciais na interface entre o enxerto e o leito receptor, acelerando o processo de incorporação. Os resultados tomográficos mostraram menor reabsorção para o grupo perfurado (P≤0,05) e ambos os grupos mostraram altas taxas de densidade óssea aos 60 dias. Estas evidências são corroboradas pelos resultados imunoistoquímicos que mostraram maior marcação de proteínas ligadas a revascularização e osteogênese (VEGF, OPN, TRAP e ALP) no grupo perfurado. Esses achados indicam que o volume ósseo de enxertos da calota craniana é mais bem conservado quando o leito receptor é perfurado, provavelmente em razão de uma mais efetiva revascularização do enxerto e maior deposição óssea. / Several studies have discussed factors that govern the longevity of onlay bone grafts. However, little information has been made available on molecular events that occur over time. Cranial bone grafts have been reported to produce greater responses compared to other donor regions in maxillofacial reconstructions, but necessary scientific verification was still lacking. The objectives of this study are (1) to study the morphological pattern of cranial onlay bone grafts and compare them to the biological events through immunohistochemical responses, and (2) to establish the effects of perforations on maintaining the volume and bone density of the receptor bed. Sixty New Zealand White rabbits were submitted to cranial onlay bone grafts of the mandible. In thirty rabbits, the receptor bed was perforated (perforated group), while for the remaining specimens the bed was kept intact (non-perforated group). Six animals from each group were culled at 5, 7, 10, 20 and 60 days after surgery. Histological cuts from the grafted area were prepared for immunohistochemical and histological analyses. During the immunohistochemical evaluation, markers were found for proteins Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor-ß ligand (RANKL), Alkaline Phosphatase (ALP), Osteopontin (OPN), Vascular Endothelial Growth Factor (VEGF), Tartrate-Resistant Acid Phosphatase (TRAP), Type I Collagen (COL I) and Osteocalcin (OC). The tomography examination (CT scan) was conducted after surgery and at culling. The histological findings revealed that the perforations contributed to higher bone deposition during the initial stages at the graft-receptor bed interface, accelerating the incorporation process. The results of the CT scan showed lower resorption for the perforated group (P≤0.05), and both groups showed high bone density rates at 60 days. This set of evidence is corroborated by the immunohistochemical results, which showed more markers of proteins associated with revascularization and osteogenesis (VEGF, OPN, TRAP and ALP) in the perforated group. These findings indicate that the bone volume of cranial dome grafts is better maintained when the receptor bed is perforated, probably resulting from more effective graft revascularization and greater bone deposition.

O presente estudo é uma coorte contemporânea de 49 pacientes (51 quadris) submetidos à reconstrução acetabular com enxerto ósseo liofilizado humano ou bovino, picado e impactado, associado a reforço acetabular. Foi realizado no Serviço de Ortopedia e Traumatologia do Hospital de Clínicas de Porto Alegre (HCPA), no período de maio de 1997 a fevereiro de 2005. Os pacientes foram divididos em dois grupos: o grupo 1 (n=26) foi composto pelos que receberam enxerto ósseo liofilizado de origem humana e o grupo 2 (n=25), por aqueles que receberam enxerto de origem bovina. O reforço utilizado em todos os casos foi da MDT® (SP-Brasil). O tempo médio de seguimento foi de 55 e 49 meses respectivamente. Os enxertos ósseos purificados e liofilizados foram produzidos pelo Banco de Tecidos do HCPA. A análise clínica baseou-se no escore de Merle d’Aubigné e Postel e a radiográfica, nos critérios de Conn et al.para osteointegração dos enxertos que avalia a radiolucência, a densidade, a formação de trabeculado ósseo e a migração do componente. Não foram encontradas diferenças clínicas ou radiográficas relevantes entre os grupos, obtendo-se em torno de 88,5 e 76% de integração do enxerto. Estes resultados são comparáveis aos relatados na literatura com o uso de enxerto alógeno congelado e estimulam a continuidade da pesquisa sobre enxertos liofilizados de origem humana e bovina. / Background: this is a cohort trial of 49 patients (51 hips) submitted to revision acetabular component of total hip arthroplasty, using impacted human and bovine freeze-dried cancellous bone grafts and reinforcement device. The study was carried out in the Hospital de Clínicas de Porto Alegre (HCPA) from May 1997 to February 2005. The aim of the study was to compare clinical and radiographic graft incorporation capability between human and bovine freeze-dried bone grafts. Patients and Methods: the patients were divided in two groups: Group 1 (n=26) was composed by those receiving human grafts, and Group 2 (n=25), bovine grafts. The follow-up average was 55 and 49 months. The grafts were purified and freeze-dried at the Tissue Bank of the HCPA.The clinical analysis was based on the score of Merle d’Aubigné and Postel; and the radiographic analysis in an established score based in Conn’s et al. criteria for radiographic bone incorporation. Results: no clinical or radiographic differences were observed between the groups and both groups showed an overall rate of 88.5 and 76% of graft integration. Conclusion: these results are comparable to those reported in the literature with the use of deep-frozen grafts. Therefore, bovine and human freeze-dried grafts can be safely and adequately used in acetabular revision in total hip arthroplasty.

O presente estudo é uma coorte contemporânea de 49 pacientes (51 quadris) submetidos à reconstrução acetabular com enxerto ósseo liofilizado humano ou bovino, picado e impactado, associado a reforço acetabular. Foi realizado no Serviço de Ortopedia e Traumatologia do Hospital de Clínicas de Porto Alegre (HCPA), no período de maio de 1997 a fevereiro de 2005. Os pacientes foram divididos em dois grupos: o grupo 1 (n=26) foi composto pelos que receberam enxerto ósseo liofilizado de origem humana e o grupo 2 (n=25), por aqueles que receberam enxerto de origem bovina. O reforço utilizado em todos os casos foi da MDT® (SP-Brasil). O tempo médio de seguimento foi de 55 e 49 meses respectivamente. Os enxertos ósseos purificados e liofilizados foram produzidos pelo Banco de Tecidos do HCPA. A análise clínica baseou-se no escore de Merle d’Aubigné e Postel e a radiográfica, nos critérios de Conn et al.para osteointegração dos enxertos que avalia a radiolucência, a densidade, a formação de trabeculado ósseo e a migração do componente. Não foram encontradas diferenças clínicas ou radiográficas relevantes entre os grupos, obtendo-se em torno de 88,5 e 76% de integração do enxerto. Estes resultados são comparáveis aos relatados na literatura com o uso de enxerto alógeno congelado e estimulam a continuidade da pesquisa sobre enxertos liofilizados de origem humana e bovina. / Background: this is a cohort trial of 49 patients (51 hips) submitted to revision acetabular component of total hip arthroplasty, using impacted human and bovine freeze-dried cancellous bone grafts and reinforcement device. The study was carried out in the Hospital de Clínicas de Porto Alegre (HCPA) from May 1997 to February 2005. The aim of the study was to compare clinical and radiographic graft incorporation capability between human and bovine freeze-dried bone grafts. Patients and Methods: the patients were divided in two groups: Group 1 (n=26) was composed by those receiving human grafts, and Group 2 (n=25), bovine grafts. The follow-up average was 55 and 49 months. The grafts were purified and freeze-dried at the Tissue Bank of the HCPA.The clinical analysis was based on the score of Merle d’Aubigné and Postel; and the radiographic analysis in an established score based in Conn’s et al. criteria for radiographic bone incorporation. Results: no clinical or radiographic differences were observed between the groups and both groups showed an overall rate of 88.5 and 76% of graft integration. Conclusion: these results are comparable to those reported in the literature with the use of deep-frozen grafts. Therefore, bovine and human freeze-dried grafts can be safely and adequately used in acetabular revision in total hip arthroplasty.

O presente estudo é uma coorte contemporânea de 49 pacientes (51 quadris) submetidos à reconstrução acetabular com enxerto ósseo liofilizado humano ou bovino, picado e impactado, associado a reforço acetabular. Foi realizado no Serviço de Ortopedia e Traumatologia do Hospital de Clínicas de Porto Alegre (HCPA), no período de maio de 1997 a fevereiro de 2005. Os pacientes foram divididos em dois grupos: o grupo 1 (n=26) foi composto pelos que receberam enxerto ósseo liofilizado de origem humana e o grupo 2 (n=25), por aqueles que receberam enxerto de origem bovina. O reforço utilizado em todos os casos foi da MDT® (SP-Brasil). O tempo médio de seguimento foi de 55 e 49 meses respectivamente. Os enxertos ósseos purificados e liofilizados foram produzidos pelo Banco de Tecidos do HCPA. A análise clínica baseou-se no escore de Merle d’Aubigné e Postel e a radiográfica, nos critérios de Conn et al.para osteointegração dos enxertos que avalia a radiolucência, a densidade, a formação de trabeculado ósseo e a migração do componente. Não foram encontradas diferenças clínicas ou radiográficas relevantes entre os grupos, obtendo-se em torno de 88,5 e 76% de integração do enxerto. Estes resultados são comparáveis aos relatados na literatura com o uso de enxerto alógeno congelado e estimulam a continuidade da pesquisa sobre enxertos liofilizados de origem humana e bovina. / Background: this is a cohort trial of 49 patients (51 hips) submitted to revision acetabular component of total hip arthroplasty, using impacted human and bovine freeze-dried cancellous bone grafts and reinforcement device. The study was carried out in the Hospital de Clínicas de Porto Alegre (HCPA) from May 1997 to February 2005. The aim of the study was to compare clinical and radiographic graft incorporation capability between human and bovine freeze-dried bone grafts. Patients and Methods: the patients were divided in two groups: Group 1 (n=26) was composed by those receiving human grafts, and Group 2 (n=25), bovine grafts. The follow-up average was 55 and 49 months. The grafts were purified and freeze-dried at the Tissue Bank of the HCPA.The clinical analysis was based on the score of Merle d’Aubigné and Postel; and the radiographic analysis in an established score based in Conn’s et al. criteria for radiographic bone incorporation. Results: no clinical or radiographic differences were observed between the groups and both groups showed an overall rate of 88.5 and 76% of graft integration. Conclusion: these results are comparable to those reported in the literature with the use of deep-frozen grafts. Therefore, bovine and human freeze-dried grafts can be safely and adequately used in acetabular revision in total hip arthroplasty.

Vários estudos têm abordado fatores que governam a longevidade dos enxertos ósseos \"onlay\". Entretanto, poucas informações têm sido disponibilizadas sobre eventos moleculares que ocorrem ao longo do tempo. Os enxertos de calota craniana têm sido reportados produzir respostas superiores em relação a outras regiões doadoras nas reconstruções maxilo-faciais, mas sem a devida comprovação científica. Este estudo tem por objetivos (1) estudar o padrão morfológico de enxertos ósseos \"onlay\" de calota craniana e compará-los com os eventos biológicos através de respostas imunoistoquímicas e (2) estabelecer os efeitos das perfurações no leito receptor sobre a manutenção do volume e densidade óssea. Sessenta coelhos do tipo New-Zealand White foram submetidos à enxertia óssea \"onlay\" de calota craniana na mandíbula. Em trinta coelhos o leito receptor foi perfurado (grupo perfurado) enquanto nos demais o leito foi mantido intacto (grupo não perfurado). Seis animais de cada grupo foram sacrificados aos 5, 7, 10, 20 e 60 dias após a cirurgia. Cortes histológicos foram preparados da região enxertada para análises imunoistoquímica e histológica. Na avaliação imunoistoquímica se observou marcações das proteínas Osteoprotegerina (OPG), \"Receptor Activator of Nuclear Factor-ß ligand\" (RANKL), Fosfatase Alcalina (ALP), Osteopontina (OPN), \"Vascular Endothelial Growth Factor\" (VEGF), \"Tartrate-Resistant Acid Phosphatase\" (TRAP), Colágeno do tipo I (COL I) e Osteocalcina (OC). O exame tomográfico foi realizado após a cirurgia e no sacrifício dos animais. Os achados histológicos revelaram que as perfurações contribuíram para uma maior deposição óssea nos períodos iniciais na interface entre o enxerto e o leito receptor, acelerando o processo de incorporação. Os resultados tomográficos mostraram menor reabsorção para o grupo perfurado (P≤0,05) e ambos os grupos mostraram altas taxas de densidade óssea aos 60 dias. Estas evidências são corroboradas pelos resultados imunoistoquímicos que mostraram maior marcação de proteínas ligadas a revascularização e osteogênese (VEGF, OPN, TRAP e ALP) no grupo perfurado. Esses achados indicam que o volume ósseo de enxertos da calota craniana é mais bem conservado quando o leito receptor é perfurado, provavelmente em razão de uma mais efetiva revascularização do enxerto e maior deposição óssea. / Several studies have discussed factors that govern the longevity of onlay bone grafts. However, little information has been made available on molecular events that occur over time. Cranial bone grafts have been reported to produce greater responses compared to other donor regions in maxillofacial reconstructions, but necessary scientific verification was still lacking. The objectives of this study are (1) to study the morphological pattern of cranial onlay bone grafts and compare them to the biological events through immunohistochemical responses, and (2) to establish the effects of perforations on maintaining the volume and bone density of the receptor bed. Sixty New Zealand White rabbits were submitted to cranial onlay bone grafts of the mandible. In thirty rabbits, the receptor bed was perforated (perforated group), while for the remaining specimens the bed was kept intact (non-perforated group). Six animals from each group were culled at 5, 7, 10, 20 and 60 days after surgery. Histological cuts from the grafted area were prepared for immunohistochemical and histological analyses. During the immunohistochemical evaluation, markers were found for proteins Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor-ß ligand (RANKL), Alkaline Phosphatase (ALP), Osteopontin (OPN), Vascular Endothelial Growth Factor (VEGF), Tartrate-Resistant Acid Phosphatase (TRAP), Type I Collagen (COL I) and Osteocalcin (OC). The tomography examination (CT scan) was conducted after surgery and at culling. The histological findings revealed that the perforations contributed to higher bone deposition during the initial stages at the graft-receptor bed interface, accelerating the incorporation process. The results of the CT scan showed lower resorption for the perforated group (P≤0.05), and both groups showed high bone density rates at 60 days. This set of evidence is corroborated by the immunohistochemical results, which showed more markers of proteins associated with revascularization and osteogenesis (VEGF, OPN, TRAP and ALP) in the perforated group. These findings indicate that the bone volume of cranial dome grafts is better maintained when the receptor bed is perforated, probably resulting from more effective graft revascularization and greater bone deposition.

Bone formation and bone healing were studied in the mandible, tibia and skull bones in adult, healthy and estrogen deficient rabbits implanted with different bone substitutes. In the first study an evaluation of the differences in bone regeneration in and around solid (Alveograf *) and porous hydroxyapatite (Interpore 200*) was undertaken. The implant material was placed into experimentally made bone defects and in half of the defects hydroxyapatite was mixed with a fibrin sealant (Tisseel *). The material alone or mixed with Tisseel was also placed subperiostally in the mandible. The observation time was six month. No difference in bone regeneration was found between solid or porous hydroxyapatite granulas and the addition of Tisseel* did not seem to disturb the bone healing process. The implant material placed subperiostally did not induce bone formation nor did it provoke any bone resorption. The addition of Tisseel made the implant material much easier to handle and retain in the tissue during surgery. Bone healing around hydroxyapatite implants was also evaluated in the second study. Experimental cavities in the mandible and tibia were filled with hydroxyapatite in granules or blocks (Interpore 200*) but now with or without autolyzed, antigen-extracted, allogeneic bone (AAA). Also in this study Tisseel* was used to facilitate the handling of the material. All cavities implanted with AAA-bone, regardless of the combination with hydroxyapatite or Tisseel, demonstrated excessive bone formation resembling exostosis formation. Thus, hydroxyapatite, both as granules and blocks, can be successfully combined with AAA bone utilizing the bone inductive capacity of AAA bone. The same model was used to study the healing in ovariectomized animals in the third study. Bone cavities were implanted with or without AAA bone and left to heal. The results indicate that the osteoinductive capacity of AAA bone is in operation also in animals deprived of a normal estrogen production. The effect of using AAA bone prior to implant insertion was studied in paper four. The bone-implant contact was significant higher when AAA bone had been used. The implant stability did not seem to be affected. In paper five defects were made in skull and tibial bone in estrogen deficient animals. The deficiency of estrogen was confirmed through blood analysis, the decrease in the weight of uterus and bone mineral density. The whole body scanning with DEXA showed that the ovariectomized animals developed osteopenia. Various degree of bone formation was seen in the defects due to the influence of the bone inductive substance AAA bone. The studies indicate that a conductive material like hydroxyapatite in granules or blocks could be useful in oral reconstructive surgery. The combination with AAA bone enhanced the bone formation in calvarial and tibial bone in healthy and estrogen deficient animals. Tisseel* could be used to facilitate handling and retention of the material in the intended position during the healing process without negative effects.