"Bring Your Own Device"-A New Approach to Wearable Outcome Assessment in Trauma.

Background and Objectives: Outcome data from wearable devices are increasingly used in both research and clinics. Traditionally, a dedicated device is chosen for a given study or clinical application to collect outcome data as soon as the patient is included in a study or undergoes a procedure. The current study introduces a new measurement strategy, whereby patients' own devices are utilized, allowing for both a pre-injury baseline measure and ability to show achievable results. Materials and Methods: Patients with a pre-existing musculoskeletal injury of the upper and lower extremity were included in this exploratory, proof-of-concept study. They were followed up for a minimum of 6 weeks after injury, and their wearable outcome data (from a smartphone and/or a body-worn sensor) were continuously acquired during this period. A descriptive analysis of the screening characteristics and the observed and achievable outcome patterns was performed. Results: A total of 432 patients was continuously screened for the study, and their screening was analyzed. The highest success rate for successful inclusion was in younger patients. Forty-eight patients were included in the analysis. The most prevalent outcome was step count. Three distinctive activity data patterns were observed: patients recovering, patients with slow or no recovery, and patients needing additional measures to determine treatment outcomes. Conclusions: Measuring outcomes in trauma patients with the Bring Your Own Device (BYOD) strategy is feasible. With this approach, patients were able to provide continuous activity data without any dedicated equipment given to them. The measurement technique is especially suited to particular patient groups. Our study's screening log and inclusion characteristics can help inform future studies wishing to employ the BYOD design.

Revision Hip Arthroplasty Using a Modular, Cementless Femoral Stem: Intermediate-Term Follow-Up.

BACKGROUND: Modular femoral stem provides flexibility in femoral reconstruction, ensuring improved "fit and fill". However, there are risks of junction failure and corrosion, as well as cost concerns in the use of modular femoral stems. METHODS: We reviewed prospectively-gathered clinical and radiographic data on revision total hip arthroplasties (THAs) performed from 2001-2007 using modular, cementless femoral component performed by the 2 senior authors. Patients with a minimum follow-up of 7 years were included in this study. RESULTS: Sixty-four patients (68 hips) with a median age of 68 ± 14 years (range 40-92 years) at revision THA were included. The median follow-up was 11.0 ± 1.8 years (range 7-14). Harris hip score, femoral stem subsidence, and stem osseointegration were recorded. The Harris hip score improved from an average of 38.1-80.1 (P < .01). Five hips had one or more dislocations. Seven patients underwent reoperations, 3 of which did not involve the stem. Four stems required revision because of infection, recurrent dislocation, or suboptimal implant position. Survival rates for any reasons and revision for femoral stems were 90% and 94%, respectively, at the most recent follow-up. Four stems subsided more than 5 mm, but established stable osseointegration thereafter. Seven nonloose stems (10.2%) demonstrated radiolucent lines in Gruen zones 1 and 7. No complications regarding the modular junction were encountered. CONCLUSION: Modular, cementless, extensively porous-coated femoral components have demonstrated intermediate-term clinical and radiographic success. Initial distal intramedullary fixation ensures stability, and proximal modularity further maximizes fit and fill.

Wearable Sensors in Other Medical Domains with Application Potential for Orthopedic Trauma Surgery-A Narrative Review.

The use of wearable technology is steadily increasing. In orthopedic trauma surgery, where the musculoskeletal system is directly affected, focus has been directed towards assessing aspects of physical functioning, activity behavior, and mobility/disability. This includes sensors and algorithms to monitor real-world walking speed, daily step counts, ground reaction forces, or range of motion. Several specific reviews have focused on this domain. In other medical fields, wearable sensors and algorithms to monitor digital biometrics have been used with a focus on domain-specific health aspects such as heart rate, sleep, blood oxygen saturation, or fall risk. This review explores the most common clinical and research use cases of wearable sensors in other medical domains and, from it, derives suggestions for the meaningful transfer and application in an orthopedic trauma context.

Use of Wearable Technology to Measure Activity in Orthopaedic Trauma Patients: A Systematic Review.

Background: Patient-Reported Outcome Measures (PROMs) are widely used for measurement of functional outcomes after orthopaedic trauma. However, PROMs rely on patient collaboration and suffer from various types of bias. Wearable Activity Monitors (WAMs) are increasingly used to objectify functional assessment. The objectives of this systematic review were to identify and characterise the WAMs technology and metrics currently used for orthopaedic trauma research. Methods: PubMed and Embase biomedical literature search engines were queried. Eligibility criteria included: Human clinical studies published in the English language between 2010 and 2019 involving fracture management and WAMs. Variables collected from each article included: Technology used, vendor/product, WAM body location, metrics measured, measurement time period, year of publication, study geographic location, phase of treatment studied, fractures studied, number of patients studied, sex and age of the study subjects, and study level of evidence. Six investigators reviewed the resulting papers. Descriptive statistics of variables of interest were used to analyse the data. Results: One hundred and thirty-six papers were available for analysis, showing an increasing trend of publications per year. Accelerometry followed by plantar pressure insoles were the most commonly employed technologies. The most common location for WAM placement was insoles, followed by the waist. The most commonly studied fracture type was hip fractures followed by fragility fractures in general, ankle, "lower extremity", and tibial fractures. The rehabilitation phase following surgery was the most commonly studied period. Sleep duration, activity time or step counts were the most commonly reported WAM metrics. A preferred, clinically validated WAM metric was not identified. Conclusions: WAMs have an increasing presence in the orthopaedic trauma literature. The optimal implementation of this technology and its use to understand patients' pre-injury and post-injury functions is currently insufficiently explored and represents an area that will benefit from future study. Systematic review registration number: PROSPERO ID:210344. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00629-0.

A review of the efficacy of intraarticular hip injection for patients with hip osteoarthritis: To inject or not to inject in hip osteoarthritis?

Hip injection (HI) for osteoarthritis (OA) are in vogue nowadays. Corticosteroids (CSs) and hyaluronic acid (HA) gel are the two most common agents injected into the hip. Off late, platelet-rich plasma (PRP), mesenchymal stem cell (MSC), bone marrow aspirate concentrate (BMAC), local anesthetic (LA) agents, non-steroidal anti-inflammatory drugs (NSAIDs) and their different combinations have also been injected in hips to provide desired pain relief. However, there is a group of clinicians who vary of these injections. A search of the literature was performed on PubMed, Cochrane Library, and DOAJ using the keywords "hip osteoarthritis injection". Data were analyzed and compiled. Intraarticular CSs are effective in providing the desired pain relief in OA hip, but repeated injections should be avoided and the interval between HI and hip arthroplasty must be kept for more than three months. Methylprednisolone or triamcinolone are combined with 1% lidocaine or 0.5% bupivacaine. Chondrotoxic effects of LA is a concern. Although national guidelines do not favor the use of HA for hip OA, numerous publications have favored its usage for a moderate grade of OA. The PRP, MSC, and BMAC are treatment options with great potential; however, currently, the evidence is conflicting on their role in hip OA. There is always a risk of septic arthritis, particularly when aseptic precautions are not followed, and clinicians must vary of this complication.

Wearable technology in orthopedic trauma surgery - An AO trauma survey and review of current and future applications.

The use of wearable sensors to track activity is increasing. Therefore, a survey among AO Trauma members was conducted to provide an overview of their current utilization and determine future needs and directions. A cross sectional expert opinion survey was administered to members of AO Trauma. Respondents were surveyed concerning their experience, subspeciality, current use characteristics, as well as future needs concerning wearable technology. Three hundred and thirty-three survey sets were available for analysis (Response Rate 16.2%). 20.7% of respondents already use wearable technology as part of their clinical treatment. The most prevalent technology was accelerometry combined with smartphones (75.4%) to measure general patient activity. To facilitate the use of wearable technology in the future, the most pressing issues were cost, patient compliance and validity of results. Wearable activity monitors are currently being used in trauma surgery. Surgeons employing these technologies mostly measure simple activity or activity associated parameters. Cost was the greatest perceived barrier to implementation. Further research, especially concerning the interpretation of the outcome values obtained, is required to facilitate wearable activity monitoring as an objective patient outcome measurement tool.

Comparison of in vitro biocompatibility of NanoBone(®) and BioOss(®) for human osteoblasts.

INTRODUCTION: Scaffolds for bone tissue engineering seeded with the patient's own cells might be used as a preferable method to repair bone defects in the future. With the emerging new technologies of nanostructure design, new synthetic biomaterials are appearing on the market. Such scaffolds must be tested in vitro for their biocompatibility before clinical application. However, the choice between a natural or a synthetic biomaterial might be challenging for the doctor and the patient. In this study, we compared the biocompatibility of a synthetic bone substitute, NanoBone(®) , to the widely used natural bovine bone replacement material BioOss(®) . MATERIAL AND METHODS: The in vitro behaviour of human osteoblasts on both materials was investigated. Cell performance was determined using scanning electron microscopy (SEM), cell vitality staining and four biocompatibility tests (LDH, MTT, WST, BrdU). RESULTS: We found that both materials showed low cytotoxicity and good biocompatibility. The MTT proliferation test was superior for Nanobone(®) . DISCUSSION: Both scaffolds caused only little damage to human osteoblasts and justify their clinical application. However, NanoBone(®) was able to support and promote proliferation of human osteoblasts slightly better than BioOss(®) in our chosen test set-up. The results may guide doctors and patients when being challenged with the choice between a natural or a synthetic biomaterial. Further experiments are necessary to determine the comparison of biocompatibility in vivo.

Novel ceramic bone replacement material CeraBall seeded with human mesenchymal stem cells.

OBJECTIVES: Hydroxyapatite (HA) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. A recently developed material for bone replacement is CeraBall, which is a mixed HA-TCP scaffold available as porous spherical scaffolds of diameter 4 and 6 mm. Before their use as bone replacement materials in vivo, in vitro testing of these scaffolds is necessary. The goal of this study was to characterise 4 and 6 mm CeraBall scaffolds in vitro with a view to their future use as bone replacement materials. MATERIALS AND METHODS: The proliferation of human mesenchymal stromal cells (hMSCs) seeded on CeraBall scaffolds was evaluated quantitatively using the WST [Water soluble tetrazolium ((4-[3-(4- Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate)] test and qualitatively by scanning electron microscopy (SEM). In addition, the standard MTT [(3-(4, 5-Dimenthylthiazol-2-Y1)-2, 5-Diphenyltetrazolium bromide)] biocompatibility test and cell vitality staining were performed using hMSCs. CeraBall scaffolds were also tested for their mechanical properties. RESULTS: SEM and WST test results showed that hMSCs proliferated on CeraBall scaffolds over the course of 9 days. Proliferation was similar to that seen on tissue culture polystyrene (control). Cells showed a well-spread morphology and formed 'sheets' on the surface of scaffolds. Invasion of pores was observed. Good biocompatibility was demonstrated by MTT test results and cell vitality staining. Scaffolds of both 4 and 6 mm were able to withstand compressive loads of 5 N. CONCLUSIONS: CeraBall scaffolds show good biocompatibility in vitro for hMSCs. This opens the way for in vivo applications.

Biocompatibility of individually designed scaffolds with human periosteum for use in tissue engineering.

UNLABELLED: The aim of this study was to evaluate and compare the biocompatibility of computer-assisted designed (CAD) synthetic hydroxyapatite (HA) and tricalciumphosphate (TCP) blocks and natural bovine hydroxyapatite blocks for augmentations and endocultivation by supporting and promoting the proliferation of human periosteal cells. Human periosteum cells were cultured using an osteogenic medium consisting of Dulbecco's modified Eagle medium supplemented with fetal calf serum, Penicillin, Streptomycin and ascorbic acid at 37 degrees C with 5% CO(2). Three scaffolds were tested: 3D-printed HA, 3D-printed TCP and bovine HA. Cell vitality was assessed by Fluorescein Diacetate (FDA) and Propidium Iodide (PI) staining, biocompatibility with LDH, MTT, WST and BrdU tests, and scanning electron microscopy. Data were analyzed with ANOVAs. RESULTS: After 24 h all samples showed viable periosteal cells, mixed with some dead cells for the bovine HA group and very few dead cells for the printed HA and TCP groups. The biocompatibility tests revealed that proliferation on all scaffolds after treatment with eluate was sometimes even higher than controls. Scanning electron microscopy showed that periosteal cells formed layers covering the surfaces of all scaffolds 7 days after seeding. CONCLUSION: It can be concluded from our data that the tested materials are biocompatible for periosteal cells and thus can be used as scaffolds to augment bone using tissue engineering methods.

Antimicrobial Peptide immunity protects human nasal and auricular cartilage against infection.

BACKGROUND: Despite being impervious to surveillance by the adaptive immune system because of its lack of vascularity, infection of the nasal and auricular cartilage after surgery such as rhinoplasty or otoplasty is rare. Why is this so? Our goal was to determine whether the expression of antimicrobial peptides provides a previously unrecognized nonepithelial layer of innate immune defense within the nasal and auricular cartilage. MATERIALS AND METHODS: Seven samples of nasal septum cartilage and 2 biopsies from auricular cartilage grafts were harvested during rhinoplasty and otoplasty procedures. Ten cadaveric samples of auricular and 9 samples of nasal cartilage were also obtained. Immunohistochemical staining was directed against the human beta-defensin antimicrobial peptides (hBD) 1, 2, and 3. A semiquantitative analysis was performed to measure immunoreactivity. RESULTS: All 3 human beta-defensins were detected along the perichondral line and within the cartilage matrix in the nasal and auricular samples. Areas with positive immunohistochemical staining were also detected within chondrocyte cytoplasm. CONCLUSIONS: We provide the first evidence of antimicrobial peptide expression (hBD-1, -2 and -3) within the perichondrium and cartilage matrix layers of the nasal and auricular cartilage. This previously unrecognized innate immune function of perichondrocytes and chondrocytes may explain the resistance of the nasal and auricular cartilage to infection after surgical procedures despite the absence of a vascular system.

Finding NEEMO: towards organizing smart digital solutions in orthopaedic trauma surgery.

There are many digital solutions which assist the orthopaedic trauma surgeon. This already broad field is rapidly expanding, making a complete overview of the existing solutions difficult.The AO Foundation has established a task force to address the need for an overview of digital solutions in the field of orthopaedic trauma surgery.Areas of new technology which will help the surgeon gain a greater understanding of these possible solutions are reviewed.We propose a categorization of the current needs in orthopaedic trauma surgery matched with available or potential digital solutions, and provide a narrative overview of this broad topic, including the needs, solutions and basic rules to ensure adequate use in orthopaedic trauma surgery. We seek to make this field more accessible, allowing for technological solutions to be clearly matched to trauma surgeons' needs. Cite this article: EFORT Open Rev 2020;5:408-420. DOI: 10.1302/2058-5241.5.200021.

Tissue engineering of periosteal cell membranes in vitro.

OBJECTIVES: The cultivation of bone is a major focus in tissue engineering and oral implantology. Without a periosteal layer, instant or rapid development of a substantial cortical layer is unlikely for engineered bone grafts. The aim of this study was to test the ability of four collagen membranes to support and promote the proliferation of human periosteal cells. MATERIALS AND METHODS: Human periosteum cells were cultured using an osteogenic medium consisting of Dulbecco's modified Eagle's medium supplemented with fetal calf serum, penicillin, streptomycin and ascorbic acid at 37 degrees C with 5% CO(2). Four collagen membranes served as scaffolds: Bio-Gide, Chondro-Gide, Tutodent and Ossix Plus. Cell vitality was assessed by fluorescin diacetate (FDA) and propidium iodide (PI) staining, biocompatibility with LDH and BrdU, MTT, WST tests and scanning electron microscopy (SEM). RESULTS: After 24 h, all probes showed viable periosteal cells. All biocompatibility tests revealed that proliferation on all membranes after treatment with eluate from membranes after a 24-h immersion in a serum-free cell culture medium was similar to the controls. Periosteal cells formed layers covering the surfaces of all four membranes 7 days after seeding in SEM. CONCLUSION: It can be concluded from our data that the collagen membranes can be used as scaffolds for the cultivation of periosteum layers with a view to creating cortical bone using tissue-engineering methods.

Porous polymer/hydroxyapatite scaffolds: characterization and biocompatibility investigations.

Poly-lactic-glycolic acid (PLGA) has been widely used as a scaffold material for bone tissue engineering applications. 3D sponge-like porous scaffolds have previously been generated through a solvent casting and salt leaching technique. In this study, polymer-ceramic composite scaffolds were created by immersing PLGA scaffolds in simulated body fluid, leading to the formation of a hydroxyapatite (HAP) coating. The presence of a HAP layer was confirmed using scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy in attenuated total reflection mode. HAP-coated PLGA scaffolds were tested for their biocompatibility in vitro using human osteoblast cell cultures. Biocompatibility was assessed by standard tests for cell proliferation (MTT, WST), as well as fluorescence microscopy after standard cell vitality staining procedures. It was shown that PLGA-HAP composites support osteoblast growth and vitality, paving the way for applications as bone tissue engineering scaffolds.

The mechanical integrity of in vivo engineered heterotopic bone.

Recent advances in tissue engineering have aroused interest in growth of heterotopic bone for the repair of skeletal defects. This study demonstrates an in vivo method in minipigs of engineering individual human-sized mandible replacements of heterotopic bone with a mechanical integrity similar to natural bone. Ten individualized mandible replacement scaffolds were created using computer-aided design (CAD) techniques. Five had a resorbable external scaffold made of polylactite mesh (test group 1) and five had had a non-resorbable external scaffold of titanium mesh (test group 2). The mesh scaffolds were loaded each with five BioOss blocks serving as internal scaffolds and 3.5 mg recombinant human Bone Morphogenetic Protein-7. The loaded mesh scaffolds were implanted into the latissimus dorsi muscles of five infant minipigs. After 6 weeks the mandible replacements were harvested. Core biopsy cylinders were taken from the replacements of both test groups and from the natural pig mandibles (control 1). Also, core biopsies from plain BioOss Blocks were gained (control 2). The core biopsy cylinders were loaded axially into a compression test device to evaluate the mechanical compression resistance. Additional specimen underwent histological examination. Both test groups resulted in successful bone induction with degrees of compression resistance [Test 1: 1.62 MPa (SD+/-0.73); Test 2: 1.51 MPa (SD+/-0.56)] statistically insignificant when compared to natural porcine mandibular bone [1.75 MPa (SD+/-0.69)]. This differed significantly from the much lower compression resistance seen in the unadulterated BioOss [0.92 MPa (SD+/-0.04)]. Following this, the in vivo engineered bone has a similar mechanical compression stability as natural bone.

The primordium of a biological joint replacement: Coupling of two stem cell pathways in biphasic ultrarapid compressed gel niches.

The impaired temporomandibular joint might be the first to benefit from applied tissue engineering techniques because it is small and tissue growth in larger amounts is challenging. Bone and cartilage require different competing environmental conditions to be cultivated in vitro. But coupling both the osteogenic and cartilaginous pathways of mesenchymal stem cell differentiation in homeostasis will be a key essential to grow osteochondral constructs or even the first biological joint replacement in the future. The aim of this study was to test a single source biomaterial and a single source cell type to engineer a biphasic osteochondral construct in vitro for future in vivo implantation. Ultrarapid tissue engineering techniques were used to create the biphasic matrix and primary human mesenchymal stem cells (MSCs) preconditioned in osteogenic and chondrogenic media were then seeded in opposite portions of the hyper-hydrated collagen gel in order to further substantiate the respective bone-like and cartilage-like layers thus potentially customising the collagen scaffold according to patient needs in regards to future biological joint replacements. After incubation for 7 days to allow cell growth and differentiation, mineralization of the bone-like layer was demonstrated using von Kossa staining and biochemical bone markers. The cartilage-like layer was demonstrated using alcian blue staining and biochemical cartilage markers. Integration of the bone-like and cartilage-like layers to simulate a tidemark layer was achieved through partial setting of the gels. Cell tracking was used to further confirm the establishment of distinct cartilage-like and bone-like areas within the single construct. This is the first report of one homogeneous human MSC population differentiating into dissimilar "bone-like" and "cartilage-like" zones hosted in a biphasic ultrarapid compressed gel phase niche and mimicking a primordial joint-like structure.

Proliferation assessment of primary human mesenchymal stem cells on collagen membranes for guided bone regeneration.

PURPOSE: Human mesenchymal stem cells (hMSCs) hold the potential for bone regeneration because of their self-renewing and multipotent character. The goal of this study was to evaluate the influence of collagen membranes on the proliferation of hMSCs derived from bone marrow. A special focus was set on short-term eluates derived from collagen membranes, as volatile toxic materials washed out from these membranes may influence cell behavior during the short time course of oral surgery. MATERIALS AND METHODS: The proliferation of hMSCs seeded directly on a collagen membrane (BioGide) was evaluated quantitatively using the cell proliferation reagent WST-1 (4-3-[4-iodophenyl]-2-[4-nitrophenyl]-2H-[5-tetrazolio]-1, 3--benzol-disulfonate) and qualitatively by scanning electron microscopy. Two standard biocompatibility tests, namely the lactate dehydrogenase and MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazoliumbromide) tests, were performed using hMSCs cultivated in eluates from membranes incubated for 10 minutes, 1 hour, or 24 hours in serum-free cell culture medium. The data were analyzed statistically. RESULTS: Scanning electron microscopy showed large numbers of hMSCs with well-spread morphology on the collagen membranes after 7 days of culture. The WST test revealed significantly better proliferation of hMSCs on collagen membranes after 4 days of culture compared to cells cultured on a cover glass. Cytotoxicity levels were low, peaking in short-term eluates and decreasing with longer incubation times. CONCLUSION: Porcine collagen membranes showed good biocompatibility in vitro for hMSCs. If maximum cell proliferation rates are required, a prewash of membranes prior to application may be useful.

Ceramic scaffolds produced by computer-assisted 3D printing and sintering: characterization and biocompatibility investigations.

Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. However, in general HAP and TCP scaffolds are not tailored to the exact dimensions of the defect site and are mainly used as granules or beads. Some scaffolds are available as ordinary blocks, but cannot be customized for individual perfect fit. Using computer-assisted 3D printing, an emerging rapid prototyping technique, individual three-dimensional ceramic scaffolds can be built up from TCP or HAP powder layer by layer with subsequent sintering. These scaffolds have precise dimensions and highly defined and regular internal characteristics such as pore size. External shape and internal characteristics such as pore size can be fabricated using Computer Assisted Design (CAD) based on individual patient data. Thus, these scaffolds could be designed as perfect fit replacements to reconstruct the patient's skeleton. Before their use as bone replacement materials in vivo, in vitro testing of these scaffolds is necessary. In this study, the behavior of human osteoblasts on HAP and TCP scaffolds was investigated. The commonly used bone replacement material BioOss(R) served as control. Biocompatibility was assessed by scanning electron microscopy (SEM), fluorescence microscopy after staining for cell vitality with fluorescin diacetate (FDA) and propidium iodide (PI) and the MTT, LDH, and WST biocompatibility tests. Both versions were colonised by human osteoblasts, however more cells were seen on HAP scaffolds than TCP scaffolds. Cell vitality staining and MTT, LDH, and WST tests showed superior biocompatibility of HAP scaffolds to BioOss, while BioOss was more compatible than TCP. Further experiments are necessary to determine biocompatibility in vivo. Future modifications of 3D printed scaffolds offer advantageous features for Tissue Engineering. The integration of channels could allow for vascular and nerve ingrowth into the scaffold. Also the complex shapes of convex and concave articulating joint surfaces maybe realized with these rapid prototyping techniques.

Endocultivation: does delayed application of BMP improve intramuscular heterotopic bone formation?

INTRODUCTION: The time point of Bone morphogenetic protein (BMP) delivery on matrices in vivo may play an important role. Delayed application could be advantageous as this would allow soft tissue (ST) ingrowth and vascularisation of scaffolds prior to BMP-loading. The aim of this study was to compare the application of BMP injected simultaneously during matrix implantation with delayed application four weeks after matrix implantation for endocultivation in a rat model. MATERIAL AND METHODS: Bovine hydroxyapatite blocks were placed in pouches in the Musculus latissimus dorsi in 6 Lewis rats unilaterally to allow for soft tissue ingrowth. Four weeks later, a second block was inserted on the contralateral side of each rat. At that time point, 100microg rhBMP-2 in 2ml sodium chloride was injected on both sides to induce bone formation. For eight weeks, bone regeneration was monitored by computed tomography (CT) and fluorescent labelling. RESULTS: The simultaneous and delayed BMP application groups were significantly different (p=0.01). Slightly lower bone densities were seen for the delayed BMP application with a mean of 588 Hounsfield Units (HU) (standard deviation (SD) 30HU). Simultaneous BMP application revealed slightly higher densities with a mean of 633HU (SD 30HU). The largest differences were observed when comparing bone density directly after implantation or at the end of the observation period (p<0.0001). CONCLUSION: Bone density was slightly lower in the case of delayed application of BMP-2. The increase of bone density after application of BMP-2 was similar for both groups. Thus, delayed application of BMP had no advantageous effect in this particular study design. Further studies are needed to explore if varying delays, different material designs or special BMP application devices may alter these results.