Mass Spectrometry-Based Proteomics of Poly(methylmethacrylate)-Embedded Bone.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely employed technique in proteomics research for studying the proteome biology of various clinical samples. Hard tissues, such as bone and teeth, are routinely preserved using synthetic poly(methyl methacrylate) (PMMA) embedding resins that enable histological, immunohistochemical, and morphological examination. However, the suitability of PMMA-embedded hard tissues for large-scale proteomic analysis remained unexplored. This study is the first to report on the feasibility of PMMA-embedded bone samples for LC-MS/MS analysis. Conventional workflows yielded merely limited coverage of the bone proteome. Using advanced strategies of prefractionation by high-pH reversed-phase liquid chromatography in combination with isobaric tandem mass tag labeling resulted in proteome coverage exceeding 1000 protein identifications. The quantitative comparison with cryopreserved samples revealed that each sample preparation workflow had a distinct impact on the proteomic profile. However, workflow replicates exhibited a high reproducibility for PMMA-embedded samples. Our findings further demonstrate that decalcification prior to protein extraction, along with the analysis of solubilization fractions, is not preferred for PMMA-embedded bone. The biological applicability of the proposed workflow was demonstrated using samples of human PMMA-embedded alveolar bone and the iliac crest, which revealed anatomical site-specific proteomic profiles. Overall, these results establish a crucial foundation for large-scale proteomics studies contributing to our knowledge of bone biology.

Vitality of autologous retromolar bone grafts for alveolar ridge augmentation after a 3-months healing period: A prospective histomorphometrical analysis.

OBJECTIVES: The incorporation of retromolar bone grafts used for alveolar ridge augmentation is not well understood. This prospective observational study aims to supply histomorphometrical data from bone graft biopsies taken at the time of retrieval and after a 3-month healing period using patient-matched biopsies. MATERIALS AND METHODS: In 17 patients, trephine biopsies of the graft were acquired at the time of graft retrieval and after a 3-month healing period. The biopsies were compared histomorphometrically regarding the number of osteocytes, appearance of osteocyte lacunae, quantity, surface area, and activity of the Haversian canals. RESULTS: All grafts appeared clinically stable after screw removal and 17 implants were placed. Histomorphometric analysis revealed no significant difference in the number of osteocytes (p = .413), osteocyte lacunae (p = .611), the ratio of filled/empty osteocyte lacunae (p = .467) and active Haversian canals (p = .495) between the biopsies retrieved after a 3-months healing period with those at the time of grafting. The only significant difference was noted in the mean surface area of the Haversian canals (p = .002). Specifically, the grafts post 3-month healing showed a significantly larger mean area (0.069 mm2) compared to the time of grafting (0.029 mm2). CONCLUSION: This study demonstrates, compared to other data, a high rate of vital structures in retromolar bone block grafts after 3 months of healing, exhibiting the same histological features in comparison to the biopsies from the native alveolar ridge. Standard histomorphometrical parameters, e.g., the amount of filled or empty osteocyte lacunae for the description of the vitality of the graft need to be reappraised.

In vitro assessment of internal implant-abutment connections with different cone angles under static loading using synchrotron-based radiation.

BACKGROUND: The stability of implant-abutment connection is crucial to minimize mechanical and biological complications. Therefore, an assessment of the microgap behavior and abutment displacement in different implant-abutment designs was performed. METHODS: Four implant systems were tested, three with a conical implant-abutment connection based on friction fit and a cone angle < 12 ° (Medentika, Medentis, NobelActive) and a system with an angulated connection (< 40°) (Semados). In different static loading conditions (30 N - 90º, 100 N - 90º, 200 N - 30º) the microgap and abutment displacement was evaluated using synchrotron-based microtomography and phase-contrast radioscopy with numerical forward simulation of the optical Fresnel propagation yielding an accuracy down to 0.1 µm. RESULTS: Microgaps were present in all implant systems prior to loading (0.15-9 µm). Values increased with mounting force and angle up to 40.5 µm at an off axis loading of 100 N in a 90° angle. CONCLUSIONS: In contrast to the implant-abutment connection with a large cone angle (45°), the conical connections based on a friction fit (small cone angles with < 12°) demonstrated an abutment displacement which resulted in a deformation of the outer implant wall. The design of the implant-abutment connection seems to be crucial for the force distribution on the implant wall which might influence peri-implant bone stability.

Distribution and Chemical Speciation of Exogenous Micro- and Nanoparticles in Inflamed Soft Tissue Adjacent to Titanium and Ceramic Dental Implants.

Degradation of the implant surface and particle release/formation as an inflammation catalyst mechanism is an emerging concept in dental medicine that may help explain the pathogenesis of peri-implantitis. The aim of the present study was a synchrotron-based characterization of micro- and nanosized implant-related particles in inflamed human tissues around titanium and ceramic dental implants that exhibited signs of peri-implantitis. Size, distribution, and chemical speciation of the exogenous micro- and nanosized particle content were evaluated using synchrotron µ-X-ray fluorescence spectroscopy (XRF), nano-XRF, and µ-X-ray absorption near-edge structure (XANES). Titanium particles, with variable speciation, were detected in all tissue sections associated with titanium implants. Ceramic particles were found in five out of eight tissue samples associated with ceramic implants. Particles ranged in size from micro- to nanoscale. The local density of both titanium and ceramic particles was calculated to be as high as ∼40 million particles/mm3. µ-XANES identified titanium in predominantly two different chemistries, including metallic and titanium dioxide (TiO2). The findings highlight the propensity for particle accumulation in the inflamed tissues around dental implants and will help in guiding toxicological studies to determine the biological significance of such exposures.

Horizontal bone grafting using equine-derived cancellous bone blocks is associated with severe complications: A prospective clinical and histological pilot study.

AIMS: The aim of this prospective, clinical study was to evaluate the clinical performance and histological outcome of a new equine hydroxyapatite collagenated bone block (eHAC) for horizontal bone grafting prior to implant placement. MATERIALS AND METHODS: Five patients (two male/three female) with a mean age of 51.6 years (range 22-66 years) and a reduced horizontal bone width of the alveolar ridge (mean 3.5 mm) underwent horizontal bone grafting using eHAC at 10 grafting sites. Reentry was performed 6.9 months after the horizontal grafting procedure. Clinical follow-up (mean 28.9 month) considered width gain of the alveolar ridge, soft tissue healing, and complications. To evaluate graft incorporation, four additional patients underwent histological assessment of equine blocks adjacent to autologous blocks 3 and 6 months after grafting. RESULTS: The study was terminated after graft failure was observed in four of five patients. Mean horizontal bone width had increased by 3.6 ± 1.22 mm. Three out of nine implants placed had to be removed due to graft failure. Histological evaluation revealed large amounts of soft connective tissue within the grafts (mean 67.3 ± 9.5%). The proportion of new bone formation 3 months after the lateral grafting procedure revealed an average of 8.6%, compared to 11.4% after 6 to 7 months. CONCLUSION: Lateral ridge grafting using eHAC achieved measurable horizontal width gain but revealed high rates of severe complications. CLINICAL IMPLICATIONS: Within the limitations of this study, eHAC bone blocks cannot be recommended for horizontal bone grafting.

Characterization of macrophages infiltrating peri-implantitis lesions.

OBJECTIVES: The mechanisms involved in the initiation and progression of peri-implantitis lesions are poorly understood. It was the aim to determine the content and activation status of macrophages present in human peri-implantitis lesions and compare the current findings with the macrophage polarization associated with periodontitis lesions. MATERIAL AND METHODS: A total of 14 patients were studied in this investigation. Seven were soft tissue biopsies from dental implants affected by peri-implantitis that required explantation. Seven biopsies were from chronic periodontal disease. Immunofluorescence stains were performed using biomarkers to identify macrophages (CD68+ ) undergoing M1 polarization (iNOS+ ) and M2 polarization (CD206+ ), along with Hoechst 33,342 to identify DNA content. All samples were stained and photographed, and double-positive cells for CD68 and iNOS or CD68 and CD206 were quantified. RESULTS: All peri-implantitis biopsies examined revealed a mixed population of macrophages undergoing M1 polarization and M2 polarization. Further analysis demonstrated the co-expression of iNOS and CD206, which indicates the presence of a heterogenic immune response on peri-implantitis lesions. Macrophage polarization in peri-implantitis lesions presents a distinct pattern than in periodontitis. We observed a significant increase in the population of M1 macrophages on peri-implantitis samples compared to periodontal disease samples. CONCLUSION: Our results demonstrate that peri-implantitis has higher numbers of macrophages displaying a distinct macrophage M1 polarization signature compared to periodontitis lesions. This pattern may explain, in part, the distinct nature of peri-implantitis progression vs. periodontitis in humans.

WITHDRAWN: Synchrotron-based Radiography of Conical- vs. Butt-joint Implant Abutment Connections.

Ahead of Print article withdrawn by publisher.

Differential osteopontin expression in human osteoblasts derived from iliac crest and alveolar bone and its role in early stages of angiogenesis.

In our previous study, we revealed significant differences of osteopontin (OPN) gene expression in primary human osteoblasts (HOBs) derived from iliac crest bone (iHOBs) and alveolar bone (aHOBs). The present study aims at assigning this discriminative expression to a possible biologic function. OPN is known to be involved in several pathologic and physiologic processes, among others angiogenesis. Therefore, we studied the reaction of human umbilical vein endothelial cells (HUVECs) to HOB-derived OPN regarding angiogenesis. To this end, human primary explant cultures of both bone entities from ten donors were established. Subsequent transcription analysis detected higher gene expression of OPN in iHOBs compared to aHOBs, thereby confirming the results of our previous study. This difference was particularly apparent when cultures were derived from female donors. Hence, OPN protein expression as well as the angiogenic potential of OPN was analyzed, originating from HOBs of one female donor. In accordance to the gene expression level, secreted OPN was more abundant in the supernatant of iHOBs than in aHOBs. Moreover, secreted OPN was found to stimulate migration of HUVECs, but not proliferation or tube formation. These results indicate an involvement in very early stages of angiogenesis and a functional distinction of OPN from HOBs derived from different bone entities.

Characterization of macrophage polarization in periodontal disease.

AIM: To explore the M1/M2 status of macrophage polarization from healthy, gingivitis, and periodontitis patient samples. MATERIALS AND METHODS: Gingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with haematoxylin and eosin staining. Immunofluorescence was performed using a combination of CD68 (macrophages), iNOS (M1), and CD206 (M2) in order to acquire changes in macrophage polarization at a single-cell resolution. Macrophages were quantified under microscopy using narrow wavelength filters to detect Alexa 488, Alexa 568, Alexa 633 fluorophores, and Hoechst 33342 to identify cellular DNA content. RESULTS: Gingivitis and periodontitis samples showed higher levels of macrophages compared with healthy samples. Unexpectedly, periodontitis samples displayed lower levels of macrophages dispersed in the stromal tissues compared with gingivitis samples; however, it remained higher than healthy tissues. The polarization of macrophages appears to be reduced in periodontitis and showed similar levels to those observed in healthy tissues. CONCLUSIONS: Our study found that gingivitis and periodontitis differ from each other by the levels of macrophage infiltrate, but not by changes in macrophage polarization.

Dental implants-associated release of titanium particles: A systematic review.

OBJECTIVES: The presence of titanium (Ti) particles around dental implants has been reported in the literature for decades. The prospective presence of Ti debris on soft tissues surrounding dental implants has not been systematically investigated and remains to be explored. Hence, this review aimed to evaluate the origin, presence, characteristics, and location of Ti particles in relation to dental implants. MATERIAL AND METHODS: Literature searches were conducted by two reviewers independently based on the PRISMA guidelines. The systematic review identified studies on Ti particles derived from dental implants. We evaluated several parameters, including anatomical location, and the suspected methods of Ti particles release. RESULTS: The search resulted in 141 articles, of which 26 were eligible and included in the systematic review of the literature. The investigations reported Ti and metal-like particles in the soft (i.e., epithelial cells, connective tissue, and inflammatory cells) and hard (bone crest and bone marrow) tissues around the dental implants. Shape and size of the particles varied. The current literature reported a size range from 100 nm to 54 µm identified by multiple particles identification methods. CONCLUSION: Ti particles surrounding peri-implant tissues are a common finding. Peri-implantitis sites presented a higher number of particles compared to healthy implants. The particles were mostly around the implants and inside epithelial cells, connective tissue, macrophages, and bone. Various mechanisms were described as causes of Ti release, including friction during implant insertion, corrosion of the implant surface, friction at the implant-abutment interface, implantoplasty, and several methods used for implant surface detoxification.

Metal elements in tissue with dental peri-implantitis: a pilot study.

OBJECTIVES: Dental peri-implantitis is characterized by a multifactorial etiology. The role of metal elements as an etiological factor for peri-implantitis is still unclear. The aim of this study was to investigate the incidence of metal elements in bone and mucosal tissues around dental Grade 4 CP titanium implants with signs of peri-implantitis in human patients. METHODS: In this prospective pilot study, all patients were enrolled consecutively in two study centers. Bone and soft tissue samples of patients with peri-implantitis with indication for explantation were analyzed for the incidence of different elements (Ca, P, Ti, Fe) by means of synchrotron radiation X-ray fluorescence spectroscopy (SRXRF) and polarized light microscopy (PLM). The existence of macrophages and lymphocytes in the histologic specimens was analyzed. RESULTS: Biopsies of 12 patients (seven bone samples, five mucosal samples) were included and analyzed. In nine of the 12 samples (75%), the SRXRF examination revealed the existence of titanium (Ti) and an associated occurrence with Iron (Fe). Metal particles were detected in peri-implant soft tissue using PLM. In samples with increased titanium concentration, lymphocytes were detected, whereas M1 macrophages were predominantly seen in samples with metal particles. CONCLUSION: Titanium and Iron elements were found in soft and hard tissue biopsies retrieved from peri-implantitis sites. Further histologic and immunohistochemical studies need to clarify which specific immune reaction metal elements/particles induce in dental peri-implant tissue.

Clinical trial and in-vitro study comparing the efficacy of treating bony lesions with allografts versus synthetic or highly-processed xenogeneic bone grafts.

BACKGROUND: Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. METHODS: 232 patients treated for bony lesions with ACB (n = 116) or SBS (n = 116) within a 10-year time period were included in this case-control study. Furthermore, both materials were seeded with human osteoblasts (hOB, n = 10) and analyzed by histology, for viability (AlamarBlue®) and protein expression activity (Luminex®). RESULTS: The complication rate was 14.2 %, proportion of defects without bony healing 3.6 %; neither outcome parameter differed comparing the intervention groups. Failed consolidation correlated with an increase in complications (p < 0.03). The rate of complications was further highly significant in association with the location of use (p < 0.001), but did not depend on age, ASA risk classification, BMI, smoking behavior or type of insurance. However, those factors did significantly influence the bony healing rate (p < 0.02). Complication and consolidation rates were independent of gender and the filling substances employed within the different locations. Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We observed initially increased expression of osteocalcin, osteopontin, and osteoprotegerin as well as leptin and adiponectin secretion declining after 1 week, especially in the ACB group. CONCLUSION: Although both investigated materials appeared to be similarly suitable for the treatment of skeletal lesions in-vivo and in-vitro, outcome was decisively influenced by other factors such as the site of use or epidemiological parameters.

Mass spectrometry-based proteomic applications in dental implants research.

Dental implants have been established as successful treatment options for missing teeth with steadily increasing demands. Today, the primary areas of research in dental implantology revolve around osseointegration, soft and hard tissue grafting as well as peri-implantitis diagnostics, prevention, and treatment. This review provides a comprehensive overview of the current literature on the application of MS-based proteomics in dental implant research, highlights how explorative proteomics provided insights into the biology of peri-implant soft and hard tissues and how proteomics facilitated the stratification between healthy and diseased implants, enabling the identification of potential new diagnostic markers. Additionally, this review illuminates technical aspects, and provides recommendations for future study designs based on the current evidence.

Impact of peri-implantitis on the proteome biology of crevicular fluid: A pilot study.

BACKGROUND: The proteome of the peri-implant crevicular fluid (PICF) has not been systematically investigated. The aim of the present study was to reveal the proteome biology of dental implants affected with peri-implantitis. METHODS: Patients with at least one diseased implant were included (probing depth ≥6 mm, ≥3 mm peri-implant radiological bone loss). Using sterile paper strips, samples were collected from healthy implants (I), healthy teeth (T) and peri-implantitis affected implants (P). Proteome analysis was performed using liquid chromatography - tandem mass spectrometry (LC-MS/MS) and data independent acquisition, allowing the identification and quantification of human and bacterial proteins as well as semi-specific peptides. RESULTS: A total of 38 samples from 14 patients were included in the study; 2332 different human proteins were identified across all samples. No differentially expressed proteins between T and I were found. Comparing P to I, 59 proteins were found upregulated and 31 downregulated in P with significance. Upregulated proteins included proinflammatory proteins such as immunoglobulins, dysferlin, and S100P, as well as antimicrobial proteins, for example, myeloperoxidase or azurocidin. Gene ontology analysis further revealed higher activity of immunological pathways. Proteolytic patterns indicated the activity of inflammatory proteins such as cathepsin G. A total of 334 bacterial proteins were identified and quantified. Peri-implantitis showed elevated proteolytic activity. CONCLUSION: I and T share similarities in their proteome, while diseased implants deviate strongly from healthy conditions. The PICF proteome of peri-implantitis affected sites exhibits an inflammatory fingerprint, dominated by neutrophil activity when compared with healthy implants.

Root Coverage Using a Novel Porcine Acellular Dermal Matrix: Case Reports of Different Minimally Invasive Techniques with a 3-Year Follow-up.

A recently released commercially available novel porcine acellular dermal matrix (PADM) appears to possess acceptable biologic and clinical properties to be considered as an acceptable soft tissue replacement material. The aim of these three case reports is to present the treatment of multiple gingival recession by means of different variations of the tunnel and PADM as well as the clinical outcomes obtained at 3 years postoperatively. The healing outcomes demonstrated only minor surgical complications, with minimal patient-reported discomfort. At 3 years postoperative, ideal functional and esthetic outcomes were observed. PADM seems to be a promising xenogeneic soft tissue substitute. Further studies with a higher number of patients and defects are necessary to confirm the present findings.

Comparison of the 3D-microstructure of human alveolar and fibula bone in microvascular autologous bone transplantation: a synchrotron radiation µ-CT study.

Introduction: Autologous bone transplantation is successfully used in reconstructive surgery of large/critical-sized bone defects, whereby the microvascular free fibula flap is still regarded as the gold standard for the reconstruction of such defects in the head and neck region. Here, we report the morphological and lacunar properties of patient-paired bone samples from eight patients from the jaw (AB; recipient site) and the fibula (FB; donor site) on the micron length-scale using Synchrotron µ-CT. Insights into differences and similarities between these bone structures could offer a better understanding of the underlying mechanism for successful surgical outcomes and might clear the path for optimized, nature-inspired bone scaffold designs. Methods: Spatial vessel-pore arrangements, bone morphology, fluid-simulation derived permeability tensor, osteocyte lacunar density, and lacunar morphology are compared. Results: The orientation of the vessel system indicates a homogenous vessel orientation for AB and FB. The average mineral distance (50%) to the closest vessel boundary is higher in AB than in FB (the mean is 96 µm for AB vs. 76 µm for FB; p = 0.021). Average osteocyte lacunar density is found to be higher in AB than in FB (mean 22,874 mm3 vs. 19,376 mm3 for FB; p = 0.038), which might compensate for the high distance from the mineral to the nearest vessel. No significant differences in lacunar volume are found between paired AB and FB. Discussion: A comparable vessel network and similar distribution of vessel porosity between AB and FB may allow the FB graft to exhibit a high regeneration potential when connected to AB, and this might correlate with a high osteoinductive and osteoconductive potential of FB when connected to AB. Since widely used and potent synthetic bone grafts exist, new insight into the bone structure of well-established autologous bone grafts, such as the free fibula flap, could help to improve the performance of such materials and therefore the design of 3D scaffolds.

Impurities in commercial titanium dental implants - A mass and optical emission spectrometry elemental analysis.

OBJECTIVE: Titanium (Ti) is considered bioinert and is still regarded as the "gold standard" material for dental implants. However, even 'commercial pure' Ti will contain minor fractions of elemental impurities. Evidence demonstrating the release of Ti ions and particles from 'passive' implant surfaces is increasing and has been attributed to biocorrosion processes which may provoke immunological reactions. However, Ti observed in peri-implant tissues has been shown to be co-located with elements considered impurities in biomedical alloys. Accordingly, this study aimed to quantify the composition of impurities in commercial Ti dental implants. METHODS: Fifteen commercial titanium dental implant systems were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). RESULTS: The elemental composition of implants manufactured from commercially pure grades of Ti, Ti-6Al-4V, and the TiZr alloy (Roxolid) conformed to the respective ISO/ASTM standards or manufacturers´ data (TiZr/Roxolid). However, all implants investigated included exogenous metal contaminants including Ni, Cr, Sb, and Nb to a variable extent. Other contaminants detected in a fraction of implants included As and the radionuclides U-238 and Th-232. SIGNIFICANCE: Although all Ti implant studies conformed with their standard compositions, potentially allergenic, noxious metals and even radionuclides were detected. Since there are differences in the degree of contamination between the implant systems, a certain impurity fraction seems technically avoidable. The clinical relevance of these findings must be further investigated, and an adaptation of industry standards should be discussed.

Proteomic profiling of human bone from different anatomical sites - A pilot study.

PURPOSE: The study aim is a comparative proteome-based analysis of different autologous bone entities (alveolar bone [AB], iliac cortical [IC] bone, and iliac spongiosa [IS]) used for alveolar onlay grafting. EXPERIMENTAL DESIGN: Site-matched bone samples of AB, IC, and IS were harvested during alveolar onlay grafting. Proteins were extracted using a detergent-based (sodium dodecyl sulfate) strategy and trypsinized. Proteome analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant was used for peptide-to-spectrum matching, peak detection, and quantitation. Linear models for microarray analysis (LIMMA) were used to detect differentially abundant peptides and proteins. RESULTS: A total of 1730 different proteins were identified across the 15 samples at a false discovery rate of 1%. Partial least-squares discriminant analysis approved segregation of AB, IC, and IS protein profiles. LIMMA statistics highlighted 66 proteins that were more abundant in AB then in IC (vs. 92 proteins were enriched in IC over AB). Gene Ontology enrichment analysis revealed a matrisomal versus an immune-related proteome fingerprint in AB versus IC. CONCLUSION AND CLINICAL RELEVANCE: This pilot study demonstrates an ECM protein-related proteome fingerprint in AB and an immune-related proteome fingerprint in IS and IC.

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study.

PURPOSE: The present prospective study evaluates the association between new bone formation rate in the iliac onlay graft and sex steroid hormone serum levels. METHODS: A total of 15 partially or completely edentulous postmenopausal females and 9 males with less than 5 mm height of the remaining alveolar bone underwent iliac onlay grafting followed by dental implant placement using a two-stage approach. Sex hormone binding globulin and 17ß-estradiol serum levels were investigated by electrochemiluminescence immunoassay, while total testosterone level was analyzed using radioimmunoassay. At the time of implant placement, 12 weeks after grafting, bone biopsies were obtained and analyzed histomorphometrically. Statistical analysis was performed using linear mixed models. RESULTS: Grafting procedure was successfully performed in all patients. The mean new bone formation rate was 32.5% (116 samples). In men the mean new bone formation rate (38.1%) was significantly higher (p < 0.01) than in women (27.6%). Independent of gender 17ß-estradiol and testosterone were positively associated to overall new bone formation rate, albeit a significant influence was only seen for 17ß-estradiol in men (p = 0.020). Sex hormone binding globulin had no influence on new bone formation rate (p = 0.897). There was no significant association between new bone formation rate and age (p = 0.353) or new bone formation rate and body mass index (p = 0.248). CONCLUSION: Positive association of 17ß-estradiol as well as testosterone with new bone formation rate after iliac onlay grafting indicates a role of sex steroid hormones in alveolar bone regeneration, although the observed influence was only significant for 17ß-estradiol in men.

Comparison of the 3D-Microstructure Between Alveolar and Iliac Bone for Enhanced Bioinspired Bone Graft Substitutes.

In oral- and maxillofacial bone augmentation surgery, non-vascularized grafts from the iliac crest demonstrate better clinical performance than alveolar bone grafts. The underlying mechanisms are not fully understood but are essential for the enhancement of bone regeneration scaffolds. Synchrotron Radiation µ-CT at a pixel size of 2.3 µm was used to characterize the gross morphology and the vascular and osteocyte lacuna porosity of patient-matched iliac crest/alveolar bone samples. The results suggest a difference in the spatial distribution of the vascular pore system. Fluid simulations reveal the permeability tensor to be more homogeneous in the iliac crest, indicating a more unidirectional fluid flow in alveolar bone. The average distance between bone mineral and the closest vessel pore boundary was found to be higher in alveolar bone. At the same time, osteocyte lacunae density is higher in alveolar bone, potentially compensating for the longer average distance between the bone mineral and vessel pores. The present study comprehensively quantified and compared the 3D microarchitecture of intraindividual human alveolar and iliac bone. The identified difference in pore network architecture may allow a bone graft from the iliac crest to exhibit higher regeneration potential due to an increased capacity to connect with the surrounding pore network of the residual bone. The results may contribute to understanding the difference in clinical performance when used as bone grafts and are essential for optimization of future scaffold materials.