Is intensive training with a time interval between instruction and planning CT necessary for deep inspiration breath-hold radiotherapy in breast cancer?

BACKGROUND: Breathing instruction and exercises and a time gap between training and planning CT scans (pCT) is recommended as part of deep inspiration breath-hold (DIBH) assisted radiotherapy (RT). However, this is associated with additional time expenditure. MATERIALS AND METHODS: In two of the authors' treatment centers (TC), patient training took place before the planning CT of DIBH-assisted therapy. In TC 1, a further appointment was made with a minimum interval of 2 days to perform the planning CT. At TC 2, the planning CT was performed immediately after the first patient instruction. A retrospective evaluation of the clinical parameters of the therapy was carried out to investigate the relevance of the time gap between DIBH exercises and pCT. RESULTS: A total of 72 patients were included, 35 of whom were treated in TC 1 and 37 in TC 2. In TC 1, an average interval of ~4 days was observed between patient training and planning CT, while in TC 2, training and CT were performed immediately after each other. No significant differences in radiation dose exposure of the lung on the treated side, the whole lung, or the heart were found between the two centers. Furthermore, there was no significant difference in the application of the daily RT fraction. The requirement for daily positioning checks was also the same at both treatment centers. CONCLUSION: This study does not show any advantages for a time gap between instruction/training and pCT. Skipping the time break does not deteriorate any clinically relevant endpoints.

[Increased report completeness and satisfaction with structured neurotological reporting in the interdisciplinary assessment of vertigo]. / Erhöhte Befundvollständigkeit und gesteigerte Zuweiserzufriedenheit bei strukturierter neurootologischer Befunderhebung in der interdisziplinären Schwindelabklärung.

BACKGROUND: Results of neurotological function diagnostics in the context of interdisciplinary vertigo assessment are usually formulated as free-text reports (FTR). These are often subject to high variability, which may lead to loss of information. The aim of the present study was to evaluate the completeness of structured reports (SR) and referrer satisfaction in the neurotological assessment of vertigo. MATERIALS AND METHODS: Neurotological function diagnostics performed as referrals (n = 88) were evaluated retrospectively. On the basis of the available raw data, SRs corresponding to FTRs from clinical routine were created by means of a specific SR template for neurotological function diagnostics. FTRs and SRs were evaluated for completeness and referring physician satisfaction (n = 8) using a visual analog scale (VAS) questionnaire. RESULTS: Compared to FTRs, SRs showed significantly increased overall completeness (73.7% vs. 51.7%, p < 0.001), especially in terms of patient history (92.5% vs. 66.7%, p < 0.001), description of previous findings (87.5% vs. 38%, p < 0.001), and neurotological (33.5% vs. 26.7%, p < 0.001) and audiometric function diagnostics (58% vs. 32.3%, p < 0.001). In addition, SR showed significantly increased referring physician satisfaction (VAS 8.8 vs. 4.9, p < 0.001). CONCLUSION: Neurotological SRs enable a significantly increased report completeness with higher referrer satisfaction in the context of interdisciplinary assessment of vertigo. Furthermore, SRs are particularly suitable for scientific data analysis, especially in the context of big data analyses.

Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

In major joint diseases the human synovium retains its potential to form repair cartilage.

The inner surface layer of human joints, the synovium, is a source of stem cells for the repair of articular cartilage defects. We investigated the potential of the normal human synovium to form novel cartilage and compared its chondrogenic capacity with that of two patient groups suffering from major joint diseases: young adults with femoro-acetabular impingement syndromes of the hip (FAI), and elderly individuals with osteoarthritic degeneration of the knee (OA). Synovial membrane explants of these three patient groups were induced in vitro to undergo chondrogenesis by growth factors: bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of these two. Quantitative evaluations of the newly formed cartilages were performed respecting their gene activities, as well as the histochemical, immunhistochemical, morphological and histomorphometrical characteristics. Formation of adult articular-like cartilage was induced by the BMP-2/TGF-ß1 combination within all three groups, and was confirmed by adequate gene-expression levels of the anabolic chondrogenic markers; the levels of the catabolic markers remained low. Our data reveal that the chondrogenic potential of the normal human synovium remains uncompromised, both in FAI and OA. The potential of synovium-based clinical repair of joint cartilage may thus not be impaired by age-related joint pathologies.

[Deforming endonasal mass during pregnancy]. / Deformierende endonasale Raumforderung während der Schwangerschaft.

This article presents the case of a 33-year-old woman who consulted the authors' ENT clinic in the 39th week of pregnancy with recurrent epistaxis. A livid endonasal mass was found on the left side, subtotally displacing the nose and leading to deformation of the external nose. External biopsy provided no indications of malignancy. Postpartum CT of the paranasal sinuses revealed a mass destroying the cartilaginous nasal septum. Endoscopic resection of the finding was performed with preservation of the clinically sound nasal septal cartilage. Histopathological examination revealed a capillary hemangioma, which was classified as granuloma gravidarum due to its occurrence during pregnancy.

Reconstructions of individual fish trophic geographies using isotopic analysis of eye-lens amino acids.

Fish eye lenses are a proteinaceous structure that grows by accumulating layers in a chronological manner. Each layer becomes metabolically inert, capturing the ratio of heavy/light carbon and nitrogen isotopes at time of formation. Therefore, eye lenses contain chronological isotopic records and can be used to create a temporal isotopic history throughout an individual's lifetime. We analyzed eye lens amino-acid δ15N to address spatio-temporal baseline variability and to reconstruct trophic histories of 10 individual Red Snapper. Proteins from sequential eye lens laminae were derivatized to measure 10 amino acids, from which glutamic acid (trophic) and phenylalanine (source) were used to estimate trophic positions at different points in life. Best-fitting regressions were generated to represent individual (R2 ≥ 0.89) and generalized (R2 = 0.77) trophic trajectory for Red Snapper. The resulting trophic trajectories indicated an increase in trophic position with increasing length. Until recently, there has not been a lifetime isotopic structure with enough organic nitrogen to recreate geographic histories using compound-specific stable isotope analysis of amino acids (CSIA-AA). This study confirms that eye-lens laminae can be used to reconstruct trophogeographic histories via CSIA-AA.

Trophic ontogeny of a generalist predator is conserved across space.

Consumers can influence ecological patterns and processes through their trophic roles and contributions to the flow of energy through ecosystems. However, the diet and associated trophic roles of consumers commonly change during ontogeny. Despite the prevalence of ontogenetic variation in trophic roles of most animals, we lack an understanding of whether they change consistently across local populations and broad geographic gradients. We examined how the diet and trophic position of a generalist marine predator varied with ontogeny across seven broadly separated locations (~ 750 km). We observed a high degree of heterogeneity in prey consumed without evidence of spatial structuring in this variability. However, compound-specific isotope analysis of amino acids revealed remarkably consistent patterns of increasing trophic position through ontogeny across local populations, suggesting that the roles of this generalist predator scaled with its body size across space. Given the high degree of diet heterogeneity we observed, this finding suggests that even though the dietary patterns differed, the underlying food web architecture transcended variation in prey species across locations for this generalist consumer. Our research addresses a gap in empirical field work regarding the interplay between stage-structured populations and food webs, and suggests ontogenetic changes in trophic position can be consistent in generalist consumers.

Human Bone Typing Using Quantitative Cone-Beam Computed Tomography.

INTRODUCTION: Bone typing is crucial to enable the choice of a suitable implant, the surgical technique, and the evaluation of the clinical outcome. Currently, bone typing is assessed subjectively by the surgeon. OBJECTIVE: The aim of this study is to establish an automatic quantification method to determine local bone types by the use of cone-beam computed tomography (CBCT) for an observer-independent approach. METHODS: Six adult human cadaver skulls were used. The 4 generally used bone types in dental implantology and orthodontics were identified, and specific Hounsfield unit (HU) ranges (grey-scale values) were assigned to each bone type for identification by quantitative CBCT (qCBCT). The selected scanned planes were labelled by nonradiolucent markers for reidentification in the backup/cross-check evaluation methods. The selected planes were then physically removed as thick bone tissue sections for in vitro correlation measurements by qCBCT, quantitative micro-computed tomography (micro-CT), and quantitative histomorphometry. RESULTS: Correlation analyses between the different bone tissue quantification methods to identify bone types based on numerical ranges of HU values revealed that the Pearson correlation coefficient of qCBCT with micro-CT and quantitative histomorphometry was R = 0.9 (P = .001) for all 4 bone types . CONCLUSIONS: We found that  qCBCT can reproducibly and objectively assess human bone types at implant sites.

Crystalline Biomimetic Calcium Phosphate Coating on Mini-Pin Implants to Accelerate Osseointegration and Extend Drug Release Duration for an Orthodontic Application.

Miniscrew implants (MSIs) have been widely used as temporary anchorage devices in orthodontic clinics. However, one of their major limitations is the relatively high failure rate. We hypothesize that a biomimetic calcium phosphate (BioCaP) coating layer on mini-pin implants might be able to accelerate the osseointegration, and can be a carrier for biological agents. A novel mini-pin implant to mimic the MSIs was used. BioCaP (amorphous or crystalline) coatings with or without the presence of bovine serum albumin (BSA) were applied on such implants and inserted in the metaphyseal tibia in rats. The percentage of bone to implant contact (BIC) in histomorphometric analysis was used to evaluate the osteoconductivity of such implants from six different groups (n=6 rats per group): (1) no coating no BSA group, (2) no coating BSA adsorption group, (3) amorphous BioCaP coating group, (4) amorphous BioCaP coating-incorporated BSA group, (5) crystalline BioCaP coating group, and (6) crystalline BioCaP coating-incorporated BSA group. Samples were retrieved 3 days, 1 week, 2 weeks, and 4 weeks post-surgery. The results showed that the crystalline BioCaP coating served as a drug carrier with a sustained release profile. Furthermore, the significant increase in BIC occurred at week 1 in the crystalline coating group, but at week 2 or week 4 in other groups. These findings indicate that the crystalline BioCaP coating can be a promising surface modification to facilitate early osseointegration and increase the success rate of miniscrew implants in orthodontic clinics.

The Synovium of Human Osteoarthritic Joints Retains Its Chondrogenic Potential Irrespective of Age.

The autologous synovium is a potential tissue source for local induction of chondrogenesis by tissue engineering approaches to repair articular cartilage defects that occur in osteoarthritis. It was the aim of the present study to ascertain whether the aging of human osteoarthritic patients compromises the chondrogenic potential of their knee-joint synovium and the structural and metabolic stability of the transformed tissue. The patients were allocated to one of the following two age categories: 54-65 years and 66-86 years (n = 7-11 donors per time point and experimental group; total number of donors: 64). Synovial biopsies were induced in vitro to undergo chondrogenesis by exposure to bone morphogenetic protein-2 (BMP-2) alone, transforming growth factor-ß1 (TGF-ß1) alone, or a combination of the two growth factors, for up to 6 weeks. The differentiated explants were evaluated morphologically and morphometrically for the volume fraction of metachromasia (sulfated proteoglycans), immunohistochemically for type-II collagen, and for the gene expression levels of anabolic chondrogenic markers as well as catabolic factors by a real-time polymerase chain reaction analysis. Quantitative metachromasia revealed that chondrogenic differentiation of human synovial explants was induced to the greatest degree by either BMP-2 alone or the BMP-2/TGF-ß1 combination, that is, to a comparable level with each of the two stimulation protocols and within both age categories. The BMP-2/TGF-ß1combination protocol resulted in chondrocytes of a physiological size for normal human articular cartilage, unlike the BMP-2-alone stimulation that resulted in cell sizes of terminal hypertrophy. The stable gene expression levels of the anabolic chondrogenic markers confirmed the superiority of these two stimulation protocols and demonstrated the hyaline-like qualities of the generated cartilage matrix. The gene expression levels of the catabolic markers remained extremely low. The data also confirmed the usefulness of experimental in vitro studies with bovine synovial tissue as a paradigm for human synovial investigations. Our data reveal the chondrogenic potential of the human knee-joint synovium of osteoarthritic patients to be uncompromised by aging and catabolic processes. The potential of synovium-based clinical engineering (repair) of cartilage tissue using autologous synovium may thus not be reduced by the age of the human patient. Impact statement Our data reveal that in younger and older age groups alike, synovial explants from osteoarthritic joints can be equally well induced to undergo chondrogenesis in vitro; that is, the chondrogenic potential of the human synovium is not compromised by aging. These findings imply that the autologous synovium represents an adequate tissue source for the repair of articular cartilage in clinical practice by tissue engineering approaches in human patients suffering from osteoarthritis, independent of the patient's age.

Impact of infections, preneoplasia and cancer on micronucleus formation in urothelial and cervical cells: A systematic review.

Approximately 165,000 and 311,000 individuals die annually from urothelial (UC) and cervical (CC) cancer. The therapeutic success of these cancers depends strongly on their early detection and could be improved by use of additional diagnostic tools. We evaluated the current knowledge of the use of micronucleus (MN) assays (which detect structural and numerical chromosomal aberrations) with urine- (UDC) and cervix-derived (CDC) cells for the identification of humans with increased risks and for the diagnosis of UC and CC. Several findings indicate that MN rates in UDC are higher in individuals with inflammation and schistosomiasis that are associated with increased prevalence of UC; furthermore, higher MN rates were also found in CDC in women with HPV, Candidiasis and Trichomonas infections which increase the risks for CC. Only few studies were published on MN rates in UDS in patients with UC, two concern the detection of recurrent bladder tumors. Strong correlations were found in individuals with abnormal CC cells that are scored in Pap tests and histopathological abnormalities. In total, 16 studies were published which concerned these topics. MN rates increased in the order: inflammation < ASC-US/ASC-H < LSIL < HSIL < CC. It is evident that MNi numbers increase with the risk to develop CC and with the degree of malignant transformation. Overall, the evaluation of the literature indicates that MNi are useful additional biomarkers for the prognosis and detection of CC and possibly also for UC. In regard to the diagnosis/surveillance of UC, further investigations are needed to draw firm conclusions, but the currently available data are promising. In general, further standardization of the assays is needed (i.e. definition of optimal cell numbers and of suitable stains as well as elucidation of the usefulness of parameters reflecting cytotoxicity and mitotic activity) before MN trials can be implemented in routine screening.

[Quality in the appraisal of head and neck sonography results in university hospitals-a random sample]. / Qualität in der Befundung von Kopf- und Halssonographien an Universitätskliniken ­ eine Stichprobe.

BACKGROUND: Ultrasound diagnostics are widely used and are standard for radiologists, otolaryngologists, and oral and maxillofacial surgeons in the diagnostic work-up of various pathologies. There is agreement that digital documentation is urgently needed at present to improve and standardize the quality of sonographic documentation. There are more and more publications on the implementation of standardized documentation of findings in imaging diagnostics, including head and neck sonography. OBJECTIVE: The present work aims to determine the quality of routine head and neck sonography findings on a random basis, according to the criteria of the Bavarian Association of Statutory Health Insurance Physicians (KVB) at a selection of German university otolaryngology departments (ENT). MATERIALS AND METHODS: A total of 70 randomly selected anonymized written findings including image documentation from seven ENT departments were retrospectively analyzed by an experienced KVB examiner concerning fulfilment of KVB criteria. The data were evaluated descriptively. RESULTS: Of the 70 reports, 69 were eligible for evaluation. The average documentation completeness was 80.6%. A total of 9 findings were correctly documented in full (13%). The documentation completeness of the individual departments was sorted in ascending order from 68.1% to 93%. With 88.5% vs. 75%, the hospitals with a structured report showed a higher level of completeness. In 75% of the cases the hospitals with structured reports also had digital solutions for reporting and image archiving. CONCLUSION: In general, there is potential for optimization regarding the completeness and quality of routinely prepared head and neck sonography findings at the selected university ENT departments. The implementation of structured reporting masks and the conversion of analogue documentation into digital solutions as well as digital networking with the hospital information systems, picture archiving and communication systems should be promoted. Supervision by senior doctors is required to ensure the quality of findings of inexperienced colleagues and to help to achieve standards in reporting.

Anticytokine Activity Enhances Osteogenesis of Bioactive Implants.

In dental clinical practice, systemic steroids are often applied at the end of implant surgeries to reduce postsurgical inflammation (tissue swelling, etc.) and to reduce patient discomfort. However, the use of systemic steroids is associated with generalized catabolic effects and with a temporarily reduced immunological competence. We hypothesize that by applying locally anticytokine antibodies (antitumor necrosis factor alpha and anti-interleukin-1 beta) together with a bioactive osteogenic implant at the time of the surgical intervention for the placement of a construct, we will be able to achieve the same beneficial effects as those using systemic steroids but are able to avoid the generalized antianabolic effects and the reduced immunocompetence effects, associated with the systemic use of steroids. In an adult rat model, a collagen sponge, soaked with the osteogenic agent bone morphogenetic protein-2, was used as an example for a bioactive implant material and was surgically placed subcutaneously. In the acute inflammatory phase after implantation (2 days after surgery) we investigated the local inflammatory tissue response, and 18 days postsurgically the efficiency of local osteogenesis (to assess possible antianabolic effects). We found that the negative control groups, treated postsurgically with systemic steroids, showed a significant suppression of both the inflammatory response and the osteogenetic activity, that is, they were associated with significant general antianabolic effects, even when steroids were used only at a low dose level. The local anticytokine treatment, however, was able to significantly enhance new bone formation activity, that is, the anabolic activity, over positive control values with BMP-2 only. However, the anticytokine treatment was unable to reduce the local inflammatory and swelling responses.

Induced Experimental Peri-Implantitis and Periodontitis: What Are the Differences in the Inflammatory Response?

This preliminary study investigates the differences between experimental periodontitis and peri-implantitis in a dog model, with a focus on the histopathology, inflammatory responses, and specific immunoregulatory activities driven by Th1/Th2-positive cells. Twelve dental implants were inserted into the edentulated posterior mandibles of 6 beagle dogs and were given 12 weeks for osseointegration. Experimental peri-implantitis and periodontitis (first mandible molar) were then induced using cotton-floss ligatures. Twelve weeks later, alveolar bones were quantitated by cone beam-computer tomography. Histopathologic analysis of the inflamed gingiva and periodontal tissues was performed by light microscopy, and the Th1/Th2 cell populations were investigated by flow cytometry. Peri-implantitis and periodontitis were both found to be associated with pronounced bone resorption effects, both to a similar degree vertically, but with a differential bone resorption pattern mesio-distally, and with a significantly higher and consistent bone resorption result in peri-implantitis, although with a higher variance of bone resorption in periodontitis. The histologic appearances of the inflammatory tissues were identical. The percentages of Th1/Th2 cells in the inflamed gingival tissues of both experimental peri-implantitis and periodontitis were also found to be similar. Experimental periodontitis and peri-implantitis in the dog model show essentially the same cellular pathology of inflammation. However, bone resorption was found to be significantly higher in peri-implantitis; the histopathologic changes in the periodontal tissues were similar in both groups but showed a higher interindividual variation in periodontitis and appeared more uniform in peri-implantitis. This preliminary study indicates that more focused experimental in vivo inflammation models need to be developed to better simulate the human pathology in the 2 different diseases and to have a valuable tool to investigate more specifically how novel treatments/prevention approaches may heal the differential adverse effects on bone tissue and on periodontium in periodontitis and in periimplantitis.

Toward in silico CMC: An industrial collaborative approach to model-based process development.

The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry.

Glaucoma in Phacomatosis Pigmentovascularis in a Young African Adolescent Boy: A Case Report.

BACKGROUND: Phacomatosis pigmentovascularis (PPV) has previously almost exclusively been reported in Asians and in dermatological journals. In this report, we present a case of a young black South African adolescent boy referred to our eye clinic. CASE REPORT: A 15-year-old male patient presented with gradual, painless loss of vision in his right eye. Clinical examination revealed a port-wine stain with ocular involvement on the right as well as a nevus of Ota. Fundoscopy on the right revealed an advanced glaucomatous optic disc and raised intraocular pressure. A diagnosis of glaucoma associated with PPV was made. CONCLUSION: We present the first case of PPV in an African male individual with associated glaucoma seen at our tertiary hospital.

Polymeric mesh and insulin-like growth factor 1 delivery enhance cell homing and graft-cartilage integration.

Cartilage injury, such as full-thickness lesions, predisposes patients to the premature development of osteoarthritis, a degenerative joint disease. While surgical management of cartilage lesions has improved, long-term clinical efficacy has stagnated, owing to the lack of hyaline cartilage regeneration and inadequate graft-host integration. This study tests the hypothesis that integration of cartilage grafts with native cartilage can be improved by enhancing the migration of chondrocytes across the graft-host interface via the release of chemotactic factor from a degradable polymeric mesh. To this end, a polylactide-co-glycolide/poly-ε-caprolactone mesh was designed to localize the delivery of insulin-like growth factor 1 (IGF-1), a well-established chondrocyte attractant. The release of IGF-1 (100 ng/mg) enhanced cell migration from cartilage explants, and the mesh served as critical structural support for cell adhesion, growth, and production of a cartilaginous matrix in vitro, which resulted in increased integration strength compared with mesh-free repair. Further, this neocartilage matrix was structurally contiguous with native and grafted cartilage when tested in an osteochondral explant model in vivo. These results demonstrate that this combined approach of a cell homing factor and supportive matrix will promote cell-mediated integrative cartilage repair and improve clinical outcomes of cartilage grafts in the treatment of osteoarthritis.

Enhanced biocompatibility and improved osteogenesis of coralline hydroxyapatite modified by bone morphogenetic protein 2 incorporated into a biomimetic coating.

OBJECTIVES: (1) To determine whether the biocompatibility of coralline hydroxyapatite (CHA) granules could be improved by using an octacalcium phosphate (OCP) coating layer, and/or functionalized with bone morphogenetic protein 2 (BMP-2), and (2) to investigate if BMP-2 incorporated into this coating is able to enhance its osteoinductive efficiency, in comparison to its surface-adsorbed delivery mode. METHODS: CHA granules (0.25 g per sample) bearing a coating-incorporated depot of BMP-2 (20 µg/sample) together with the controls (CHA bearing an adsorbed depot of BMP-2; CHA granules with an OCP coating without BMP-2; pure CHA granules) were implanted subcutaneously in rats (n = 6 animals per group). Five weeks later, the implants were retrieved for histomorphometric analysis to quantify the volume of newly generated bone, bone marrow, fibrous tissue and foreign body giant cells (FBGCs). The osteoinductive efficiency of BMP-2 and the rates of CHA degradation were also determined. RESULTS: The group with an OCP coating-incorporated depot of BMP-2 showed the highest volume and quality or bone, and the highest osteoinductive efficacy. OCP coating was able to reduce inflammatory responses (improve biocompatibility), and also simple adsorption of BMP-2 to CHA achieved this. CONCLUSIONS: The biocompatibility of CHA granules (reduction of inflammation) was significantly improved by coating with a layer of OCP. Pure surface adsorption of BMP-2 to CHA also reduced inflammation. Incorporation of BMP-2 into the OCP coatings was associated with the highest volume and quality of bone, and the highest biocompatibility degree of the CHA granules. CLINICAL SIGNIFICANCE: Higher osteoinductivity and improved biocompatibility of CHA can be obtained when a layer of BMP-2 functionalized OCP is deposited on the surfaces of CHA granules.