Background: The increasing need for bone grafting procedures inimplant dentistry and the introduction of a variety of bone substitutesrequire a deeper understanding of the biological response and shortandlong-term behaviour of these materials to choose the adequategraft and surgical procedure for the intended clinical application.Aims: The overall aim was to clinically and histologically studythe short- and long-term tissue reactions to and resorption of bonesubstitutes after bone augmentation.Material and methods: In paper I, dentin blocks with different demineralizationtimes were placed subperiostally in 40 rat skulls. Aftera healing period of 4 weeks the rats were sacrificed and the healingof the dentin blocks were evaluated. In paper II, eleven patients weretreated with bilateral sinus floor augmentation using biphasic calciumphosphate (BCP) on one side and deproteinized bovine bone (DPBB)on the contralateral side, acting as control. After 3 years, biopsieswere retrieved from the grafted area for histological evaluation andhistomorphometry and 62 dental implants, placed 8 months aftergraft healing, were clinically evaluated. In paper III and IV, fourteen(22 sinuses) of the included 20 patients (30 sinuses) treated withsinus floor augmentation with a mixture of 80% DPBB and 20%autogenous bone (AB) from the chin were followed throughout the10 years study period. These patients had 53 implants placed ingrafted sites and 15 implants placed in non-grafted bone. Clinicaland radiographic examinations were performed. Biopsies wereretrieved from the grafted sinuses after 11 years of graft healing for16histological evaluation and histomorphometry. The particle sizeswere compared with samples retrieved after 6 months from the samepatients and pristine particles from the manufacturer. In paper V, 13patients (14 jaws) were treated with lateral ridge augmentation using2 different mixtures of DPBB:AB (90:10 and 60:40) in a randomizedand controlled trial, designed as a split mouth study. The width andvolume changes were evaluated after 7.5 months by means of conebeam computed tomography. After 8 months of graft healing, at thetime of implant placement, biopsies were retrieved for histologicalevaluation and histomorphometry.Results: Resorption increased with increasing degree of demineralizationof dentin blocks while bone formation increased with increasingdegree of demineralization, in the latter case provided inflammationwas compensated for (paper I). After 3 years of healing the BCPparticles showed different levels of dissolution, in contrast to DPBBparticles that showed no signs of resorption. The overall implantsurvival rate was 96.8% and the success rate for implants placed inBCP and DPBB was 91.7% and 95.7% respectively (paper II). Thecumulative survival rate of the implants after 10 years was 86% andthe marginal bone loss was 1.6 mm. There was only a reduction ingraft height between 3 months and 2 years but no further reductionup to 10 years (paper III). There was no difference between the sizeof DPBB particles after 11 years compared to those measured after6 months or to particles from the manufacturer (paper IV). Thegain in width of the alveolar crest was 3.5 mm and 2.9 mm and thereduction of the grafts were 37% and 47% for the 60:40 mixtureand 90:10 mixture respectively (significant differences). There wereno histomorphometrical differences between the groups (paper V).Conclusions: Partial demineralization may provide a method foroptimizing the integration of dentin onlays. A similar degree of boneformation and bone-to-graft contact for BCP and DBB was found 3years after maxillary sinus augmentation with similar success ratesfor implants placed in both grafting materials. At 10 years follow-upafter sinus floor augmentation with 80:20 (DPBB:AB) graft, theremaining implants presented good clinical and radiological resultsand there seems to be no further graft resorption after 2 years of17graft healing. DPBB particles were found to be well integrated inlamellar bone, showing no apparent signs of resorption after 11 yearsin humans. Despite a small difference in width changes after lateralridge augmentation, the amount of AB added to DPBB did not seemto have a major impact on the graft healing and graft reduction, thusmaking it possible to install implants in all grafted sites.