Fixed-Bearing Unicompartmental Knee Arthroplasty of the Lateral Compartment: A Series of 246 Cases.

Background: Isolated osteoarthritis of the lateral compartment of the knee is less common than that of the medial compartment, resulting in significantly fewer lateral unicompartmental knee arthroplasties (UKAs) being performed. This study aimed to evaluate results of a fixed-bearing UKA for the treatment of lateral compartment osteoarthritis of the knee. Methods: A prospectively collected cohort of 255 patients undergoing fixed-bearing UKA of the lateral compartment using the Triathlon PKR (Stryker, Warsaw, IND) implant with a minimum 2-year follow-up was reviewed. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, radiographic alignment, complications, reoperations, and revisions were recorded. Patient factors and pre- and post-surgical alignment were assessed for their association with a minimum important change (MIC) of the total WOMAC score. Results: A total of 246 implants with a mean follow-up of 6.6 years (2-10.8 years) were included (4% lost to follow-up). The total WOMAC score increased from 61.3 ± 3.5 to 85.3 ± 7.5, exceeding the MIC in 215 patients (88%). Exceeding the MIC was not associated with age, body mass index, or alignment. The 5-year implant revision rate was 1.6% (3/187). Conclusions: The fixed-bearing Stryker Triathlon PKR implant for lateral UKA resulted in good clinical outcomes with a low revision rate at midterm follow-up. Body mass index, age, and pre- and post-surgical alignment did not correlate with the clinical outcome. Long-term follow-up is necessary to determine if the clinical improvement and low revision rate can be maintained.

Femoral condyle resurfacing using an inlay metal implant: low revision rate of 266 patients in a 5-10 years follow-up.

PURPOSE: To assess the clinical outcome and survival of an inlay resurfacing prosthesis for focal femoral condyle chondral and osteochondral defects. METHODS: Two hundred sixty-six patients (mean age, 38.25 years; range 25-56 years) with symptomatic femoral condyle chondral and osteochondral defects were reviewed. The mean follow-up period was 7.3 years (range 5-10 years). The medial femoral condyle was involved in 229 and the lateral condyle in 37 patients. Previous cartilage surgery was done in 235 patients. All patients were treated with focal femoral condyle resurfacing with the HemiCAP® device. The preoperative and the last follow-up values of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), 36-item Short Form Survey (SF-36) and Visual Analogue Scale (VAS) were examined. Complications, reoperation rate and survival were analyzed. RESULTS: At the last follow-up, all clinical score values showed significant improvement as compared with the corresponding preoperative values (p < 0.001). Age presented a negative correlation with KOOS (p = 0.03) and SF-36 improvement (p = 0.014). Kellgren-Lawrence grade influenced OKS (p = 0.036). BMI, gender, side, medial or lateral condyle and size did not affect the outcome. Patients who had previous biological cartilage procedures demonstrated better clinical improvement in comparison with those that did not have prior surgery (p < 0.05). Survival was 96.2% at 10 years, using as endpoint implant revision or/and progression of osteoarthritis. The cumulative hazard for any-reason reoperation was 12.0%. CONCLUSIONS: Femoral condyle resurfacing using the HemiCAP® device is an effective treatment option to address focal chondral and osteochondral defects. It can be successfully used either as a primary procedure or after prior biological cartilage reconstruction. Subjective clinical outcomes are expected to be good to excellent in mid- to long term, while reoperation and revision rates are low. Progression of osteoarthritis is the most common mode of failure; thus, patient selection is very important. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Does capsular distension and a short period of countertraction improve outcome following manipulation under anesthesia for the treatment of primary adhesive capsulitis of the glenohumeral joint?

BACKGROUND: Despite the fact that primary adhesive capsulitis of the glenohumeral joint is often considered a self-limiting condition, not all patients make a full recovery. Manipulation under anesthesia (MUA) is performed to forcibly rupture the contracted capsule in a controlled manner. However, the technique, timing, and use of additional injections are often debated. In this study, we report the outcomes following the addition of capsular distension and countertraction to MUA as a treatment for adhesive capsulitis. METHODS: We performed a retrospective case-cohort study comparing 3 groups: Group 1 underwent MUA alone (n = 54); group 2, MUA with capsular distension (n = 114); and group 3, MUA with capsular distension and countertraction (n = 167). The re-MUA rate, Constant-Murley shoulder (CMS) score, and visual analog scale (VAS) score (for pain) were measured after 6 weeks and 6 months. RESULTS: The re-MUA rate fell with the addition of both capsular distension and countertraction: 63% in group 1, 39% in group 2, and 18% in group 3. Patients in group 3 recorded the greatest improvement in the CMS score after 6 weeks (+90% vs. +68% in group 2 and +58% in group 1), with all groups showing improvements compared with before treatment. The only independent risk factor identified for re-MUA was smoking. If a second MUA was performed, the CMS (+67%) and VAS (+61%) scores improved, but at 6 months, the CMS score (74.57 ± 7.6 vs. 83.30 ± 5.5) and VAS score (10.57 ± 1.8 vs. 12.96 ± 1.5) remained inferior to those of patients who only needed a single MUA. DISCUSSION AND CONCLUSION: MUA combined with capsular distension and countertraction reduces the need for a second MUA and results in a faster improvement in functional outcome (CMS score) and reduction of pain (VAS score) compared with MUA alone or MUA with capsular distension. The results of this case-cohort study are of clinical relevance because they show that the efficacy of an MUA can be improved through relatively simple adaptations of the treatment protocol.

Focal articular surface replacement as primary treatment for focal chondral defects of the femoral condyles: A series of 157 cases.

BACKGROUND: Focal chondral defects (FCDs) of the femoral condyle are common. Treatment has heretofore primarily consisted of non-surgical and biological treatments. Focal articular surface replacement (FASR) is an emerging technique utilizing small implants to essentially fill the FCD. Here we report functional outcome and re-operation rates following FASR as a primary treatment for FCDs of the femoral condyles. METHODS: Retrospective analysis of a prospectively collected database including 327 FASR procedures was performed to identify patients who underwent FASR of the femoral condyle with a modular cementless metallic implant (HemiCAPTM) as a primary procedure. Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), SF-36 Health Status Survey (SF-36) and Visual Analog Scale (VAS) were collected before and 6 weeks, 6 months, and 4 years after surgery. Implant revision and re-operation rate were recorded. RESULTS: 157 patients were included with a mean follow-up of 9.4 ± 1.3 years (range 7.0 to 11.4 years). The average age was 40.2 ± 5.3 years, 85% involved the medial condyle, and the average defect size was 3.6 ± 0.5 cm2. Primary FASR resulted in functional improvement on the KOOS (+52%), OKS (+69%) and SF-36 (+50%) scores and a reduction in VAS scores (-70%) at 4-year follow-up. Revision rate was 0.64% and the re-operation rate was 11%. CONCLUSION: This retrospective case-series supports primary FASR with HemiCAPTM implants as an alternative to biological procedures to treat medium-sized FCDs (2.5-4 cm2) of the femoral condyle, although long-term follow-up is necessary to determine if the clinical outcome and low revision rate can be maintained.

The three-dimensional shape symmetry of the lunate and its implications.

We studied the three-dimensional (3-D) shape variations and symmetry of the lunate to evaluate whether a contralateral shape-based approach to design patient-specific implants for treatment of Kienböck's disease is accurate. A 3-D statistical shape model of the lunate was built using the computed tomography scans of 54 lunate pairs and shape symmetry was evaluated based on an intraclass correlation analysis. The lunate shape was not bilaterally symmetrical in (1) the angle scaphoid surface - radius-ulna surface, (2) the dorsal side and the length of the side adjacent to the triquetrum, (3) the orientation of the volar surface, (4) the width of the side adjacent to the scaphoid, (5) the skewness in the coronal plane and (6) the curvature of bone articulating with the hamate and capitate. These findings suggest that using the contralateral lunate to design patient-specific lunate implants may not be as accurate as it is intended.

Focal articular surface replacement of knee lesions after failed cartilage repair using focal metallic implants: A series of 132 cases with 4-year follow-up.

BACKGROUND: Focal articular lesions of the knee can be treated using several different techniques with generally good results, but failures are difficult to manage. Focal articular surface replacement (FASR) using metal implants could be a promising technique that allows defect geometry matching, congruency restoration and defect propagation prevention. METHODS: 132 patients were included who underwent FASR between January 2009 and December 2013. Three different implants were used: 1. HemiCAP®; 2. UniCAP® and 3. HemiCAP® PF Classic for trochlear lesions. Primary outcome parameter was knee function assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score with a 4-year follow-up, secondary outcomes included survivorship and complications. Statistical analyses were performed using GraphPad Prism. RESULTS: For all 132 surgeries combined (102 HemiCAP®, 11 UniCAP® and 19 HemiCAP® PF Classic implants), WOMAC scores significantly improved from 6 weeks onward until the end of the study (p < 0.001 for all time points). 4-year survival rate was 97.7%, and a re-operation rate of 12.1% was found. The HemiCAP® group revealed a slower WOMAC improvement in patients aged ≥40 years, combined with a trend towards lower final WOMAC scores and a higher re-operation rate in patients with a BMI ≥ 25. CONCLUSIONS: This report shows good to excellent clinical results of FASR as a salvage procedure after failed cartilage repair, with a low re-operation rate and a high survival of 97.7% at 4-year follow-up. Although longer follow-up is required, this could be a valuable treatment option in these challenging cases, without limiting future options for surgical interventions when deemed necessary.

Preoperative embolization in surgical treatment of long bone metastasis: a systematic literature review.

Surgery of long bone metastases is associated with a significant risk of perioperative blood loss, which may necessitate blood transfusion.Successful embolization (> 70% obliteration of vascularity) can be achieved in 36-75% of cases.The reported rate of embolization-related complications is 0-9%.Three out of six level III evidence studies showed a reduction in perioperative blood loss and/or blood transfusion requirement after preoperative embolization of renal cell carcinoma metastasis in long bones; three out of six studies did not.One level III evidence study did not show a reduction in perioperative blood loss and/or transfusion requirement after preoperative embolization of hepatocellular carcinoma metastases in long bones.There were no studies found that support preoperative embolization of thyroid metastases or other frequent long bone metastases (e.g. mamma carcinoma, lung carcinoma, or prostate carcinoma).The clinical level of evidence of the studies found is low and randomized studies taking into account primary tumour, location of metastases and type of surgery are therefore desired. Cite this article: EFORT Open Rev 2020;5:17-25. DOI: 10.1302/2058-5241.5.190013.

Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.

A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 µg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor cells. Long-term beneficial effects of osteostatin-coated, porous titanium implants on bone regeneration or mechanical strength were not established here and may require optimization of the pace and dose of osteostatin release.

Additively manufactured porous tantalum implants.

The medical device industry's interest in open porous, metallic biomaterials has increased in response to additive manufacturing techniques enabling the production of complex shapes that cannot be produced with conventional techniques. Tantalum is an important metal for medical devices because of its good biocompatibility. In this study selective laser melting technology was used for the first time to manufacture highly porous pure tantalum implants with fully interconnected open pores. The architecture of the porous structure in combination with the material properties of tantalum result in mechanical properties close to those of human bone and allow for bone ingrowth. The bone regeneration performance of the porous tantalum was evaluated in vivo using an orthotopic load-bearing bone defect model in the rat femur. After 12 weeks, substantial bone ingrowth, good quality of the regenerated bone and a strong, functional implant-bone interface connection were observed. Compared to identical porous Ti-6Al-4V structures, laser-melted tantalum shows excellent osteoconductive properties, has a higher normalized fatigue strength and allows for more plastic deformation due to its high ductility. It is therefore concluded that this is a first step towards a new generation of open porous tantalum implants manufactured using selective laser melting.

Bone regeneration performance of surface-treated porous titanium.

The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.

Inflammatory response and bone healing capacity of two porous calcium phosphate ceramics in critical size cortical bone defects.

In the present study, two open porous calcium phosphate ceramics, ß-tricalcium phosphate (ß-TCP), and hydroxyapatite (HA) were compared in a critical-sized femoral defect in rats. Previous comparisons of these two ceramics showed significantly greater osteoinductive potential of ß-TCP upon intramuscular implantation and a better performance in a spinal fusion model in dogs. Results of the current study also showed significantly more bone formation in defects grafted with ß-TCP compared to HA; however, both the ceramics were not capable of increasing bone formation to such extend that it bridges the defect. Furthermore, a more pronounced degradation of ß-TCP was observed as compared to HA. Progression of inflammation and initiation of new bone formation were assessed for both materials at multiple time points by histological and fluorochrome-based analyses. Until 12 days postimplantation, a strong inflammatory response in absence of new bone formation was observed in both ceramics, without obvious differences between the two materials. Four weeks postimplantation, signs of new bone formation were found in both ß-TCP and HA. At 6 weeks, inflammation had subsided in both ceramics while bone deposition continued. In conclusion, the two ceramics differed in the amount of bone formed after 8 weeks of implantation, whereas no differences were found in the duration of the inflammatory phase after implantation or initiation of new bone formation.

Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs) was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

Enhanced bone regeneration of cortical segmental bone defects using porous titanium scaffolds incorporated with colloidal gelatin gels for time- and dose-controlled delivery of dual growth factors.

Porous titanium scaffolds are a promising class of biomaterials for grafting large bone defects, because titanium provides sufficient mechanical support, whereas its porous structure allows bone ingrowth resulting in good osseointegration. To reinforce porous titanium scaffolds with biological cues that enhance and continue bone regeneration, scaffolds can be incorporated with bioactive gels for time- and dose-controlled delivery of multiple growth factors (GFs). In this study, critical femoral bone defects in rats were grafted with porous titanium scaffolds incorporated with nanostructured colloidal gelatin gels. Gels were loaded with bone morphogenetic protein-2 (BMP-2, 3 µg), fibroblast growth factor-2 (FGF-2, 0.6 µg), BMP-2, and FGF-2 (BMP-2/FGF-2, ratio 5:1) or were left unloaded. GF delivery was controlled by fine tuning the crosslinking density of oppositely charged nanospheres. Grafted femurs were evaluated using in vivo and ex vivo micro-CT, histology, and three-point bending tests. All porous titanium scaffolds containing GF-loaded gels accelerated and enhanced bone regeneration: BMP-2 gels gave an early increase (0-4 weeks), and FGF-2 gels gave a late increase (8-12 weeks). Interestingly, stimulatory effects of 0.6 µg FGF-2 were similar to a fivefold higher dose of BMP-2 (3 µg). BMP-2/FGF-2 gels gave more bone outside the porous titanium scaffolds than gels with only BMP-2 or FGF-2, resulted in bridging of most defects and showed superior bone-implant integrity in three-point bending tests. In conclusion, incorporation of nanostructured colloidal gelatin gels capable of time- and dose-controlled delivery of BMP-2 and FGF-2 in porous titanium scaffolds is a promising strategy to enhance and continue bone regeneration of large bone defects.

Predicting the therapeutic efficacy of MSC in bone tissue engineering using the molecular marker CADM1.

Mesenchymal stromal cells (hMSCs) are advancing into the clinic but the therapeutic efficacy of hMSCs faces the problem of donor variability. In bone tissue engineering, no reliable markers have been identified which are able to predict the bone-forming capacity of hMSCs prior to implantation. To this end, we isolated hMSCs from 62 donors and characterized systematically their in vitro lineage differentiation capacity, gene expression signature and in vivo capacity for ectopic bone formation. Our data confirms the large variability of in vitro differentiation capacity which did not correlate with in vivo ectopic bone formation. Using DNA microarray analysis of early passage hMSCs we identified a diagnostic bone-forming classifier. In fact, a single gene, CADM1, strongly correlated with the bone-forming capacity of hMSCs and could be used as a reliable in vitro diagnostic marker. Furthermore, data mining of genes expressed correlating with in vivo bone formation represented involvement in neurogenic processes and Wnt signaling. We will apply our data set to predict therapeutic efficacy of hMSCs and to gain novel insight in the process of bone regeneration. Our bio-informatics driven approach may be used in other fields of cell therapy to establish diagnostic markers for clinical efficacy.

Full-field strain measurement and fracture analysis of rat femora in compression test.

There is a growing interest in studying the fracture behavior of bones, primarily due to the increasing societal burden of osteoporotic fractures. In addition, bone is one of the most important biological materials whose fracture behavior is not yet well understood. This is partly due to the fact that bone is a complex hierarchical material, and exhibits heterogeneous, anisotropic, and viscoelastic mechanical behavior. Understanding the fracture behavior of such a complex material requires application of a full-field strain measurement technique. Digital image correlation (DIC) is a relatively new full-field strain measurement technique that can be used for measurement of 3D surface strains during mechanical testing of different types of bones. In this study, we use the DIC technique to measure the surface strains during compression testing of two groups of rat femora. The first group of femora was harvested from young animals (12 weeks), while the second group was harvested from more mature animals (26 weeks). The surface strains are measured both in the linear range and close to the fracture. Using the measured data, we assess two strain-based fracture prediction criteria, namely equivalent strain fracture criterion and fracture limit diagram, to determine whether they can consistently predict the onset of fracture. The maximum load is measured to be 296±22 N (mean±SD) for young animals and 670±123 N for mature animals. It is shown that fracture in the vast majority of cases occurs in the area of maximum tensile strain. The equivalent strain fracture criterion predicts that the fracture occurs when the equivalent strain reaches 1.04±0.02% (average±SD) for young animals and 1.39±0.24% for mature animals. The fracture limit diagram predicts that the fracture occurs once the sum of major and minor principal surface strains reaches 0.63±0.23% for young animals and -0.63±0.30% for mature animals. Based on these numbers and consistency of the criteria with the strain values recorded at the fracture locations, it is concluded that the equivalent strain fracture criterion tends to be more consistent among the tested specimens.

Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects.

Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120-µm (titanium-120) or 230-µm (titanium-230) were studied in a load-bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium-120, titanium-230, or left empty. In vivo micro-CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm(3) (titanium-120, p = 0.015) and 18.7 ± 8.0 mm(3) (titanium-230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm(3) ). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium-120) and 45% (titanium-230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects.

The influence of genetic factors on the osteoinductive potential of calcium phosphate ceramics in mice.

The efficacy of calcium phosphate (CaP) ceramics in healing large bone defects is, in general, not as high as that of autologous bone grafting. Recently, we reported that CaP ceramics with osteoinductive properties were as efficient in healing an ilium defect of a sheep as autologous bone graft was, which makes this subclass of CaP ceramics a powerful alternative for bone regeneration. Although osteoinduction by CaP ceramics has been shown in several large animal models it is sporadically reported in mice. Because the lack of a robust mouse model has delayed understanding of the mechanism, we screened mice from 11 different inbred mouse strains for their responsiveness to subcutaneous implantation of osteoinductive tricalcium phosphate (TCP). In only two strains (FVB and 129S2) the ceramic induced bone formation, and in particularly, in FVB mice, bone was found in all the tested mice. We also demonstrated that other CaP ceramics induced bone formation at the same magnitude as that observed in other animal models. Furthermore, VEGF did not significantly increase TCP induced bone formation. The mouse model here described can accelerate research of osteoinductive mechanisms triggered by CaP ceramics and potentially the development of therapies for bone regeneration.

Bone substitutes in the Netherlands - a systematic literature review.

Autologous bone grafting is currently considered as the gold standard to restore bone defects. However, clinical benefit is not guaranteed and there is an associated 8-39% complication rate. This has resulted in the development of alternative (synthetic) bone substitutes. The aim of this systematic literature review was to provide a comprehensive overview of literature data of bone substitutes registered in the Netherlands for use in trauma and orthopedic surgery. Brand names of selected products were used as search terms in three available databases: Embase, PubMed and Cochrane. Manuscripts written in English, German or Dutch that reported on structural, biological or biomechanical properties of the pure product or on its use in trauma and orthopedic surgery were included. The primary search resulted in 475 manuscripts from PubMed, 653 from Embase and 10 from Cochrane. Of these, 218 met the final inclusion criteria. Of each product, structural, biological and biomechanical characteristics as well as their clinical indications in trauma and orthopedic surgery are provided. All included products possess osteoconductive properties but differ in resorption time and biomechanical properties. They have been used for a wide range of clinical applications; however, the overall level of clinical evidence is low. The requirements of an optimal bone substitute are related to the size and location of the defect. Calcium phosphate grafts have been used for most trauma and orthopedic surgery procedures. Calcium sulphates were mainly used to restore bone defects after tumour resection surgery but offer minimal structural support. Bioactive glass remains a potential alternative; however, its use has only been studied to a limited extent.