Bone Void Filler Research Articles

Minimally Invasive Subpericranial Model: Can It Be Used to Study Bone Substitutes?

Objective: To evaluate the feasibility and effectiveness of a new approach for craniofacial augmentation by a minimally-invasive subpericranial injection. Three commercially available semi-liquid bioceramic bone-grafting materials were examined for this application in a rat model. Material and Methods: Twenty-four adult male rats were randomly assigned to undergo onlay calvarial grafting by subpericranial injection of three semi-liquid bone void fillers: Norian SRS(calcium phosphate), ChronOs InjectTM (porous beta-tricalcium phosphate), or BonePlastharvested after 24 hours to serve as controls. The rest were studied after 16 weeks. The volume fraction of the following parameters was morphometrically measured: new bone, blood vessels, residual bone filler and inflammation. Results: In all study groups (including controls), histological examination demonstrated that bone fillers were successfully delivered to the desired subpericranial space by the percutaneous injection method. New bone formation was evidenced adjacent to the cranial bone in all the study groups. The Norian filler material survived in a significantly higher volume fraction (38.4% ± 6.5%) than the ChronOs filler (18.8% ± 1.6%; P 0.0001) and the BonePlast filler (17.8% ± 1.5%; P 0.0001). New bone was formed in all groups, particularly adjacent to the interface of graft material with native bone but only to minimal extent. Conclusion: This new approach for craniomaxillofacial augmentation was successfully demonstrated in a rat model. The Norian filler (calcium phosphate) demonstrated superior space preservation abilities. This model may be further applied to test new injectable bone substitutes in the craniomaxillofacial area.

Corporate Malfeasance, Off-Label Use, and Surgeon Liability

The federal criminal case relating to the off-label use of Norian bone void filler for vertebroplasty has been well-publicized. We examined the facts of this case to understand evolving trends in federal criminal prosecution in the healthcare industry, and to address the potential liability of orthopaedic surgeons who practice off-label use of a product, especially when consulting for the industry.

Footprint and augmented anchorage

One-stage procedure for gaining adequate bone stock and rotator cuff repair. Tears of the rotator cuff in combination with bony cysts or reduced bone quality at the footprint. Allergies to contents of the bone void filler, fatty infiltration of infraspinatus and subscapularis of stage 3 and 4, narrowing of the subacromial space (< 7mm). We report a one-stage technique for footprint reconstruction in a rotator cuff tear-associated greater tuberosity cyst by augmenting the cystic lesion with an injectable, absorbable, biocompatible, fiber reinforced bone void filler in combination with a double row rotator cuff reconstruction technique. The arm is placed in a shoulder-immobilizing abduction pillow to achieve 30° abduction for a period of 4-6weeks. The physical therapy program includes passive mobilization of the affected shoulder to 60-90° flexion/abduction within the first 3weeks. During the next 3weeks, the passive mobilization is changed to active mobilization, starting with assisted exercises. Active exercises without limitation in range of motion are not allowed until the 7th week after surgery and moderate sports not until the third month post-surgery. Six patients have been treated using the presented technique. However, long term results are still missing.

Footprint reconstruction in a rotator cuff tear associated cyst of the greater tuberosity: augmented anchorage

Tears of the rotator cuff (RC) complicated by bone cysts at the footprint might represent a challenge for the shoulder surgeon. This might be additionally aggravated in elderly patients with inferior bone quality due to osteopenia or osteoporosis. In this report we present a technique for open repair of RC tears by augmenting the cystic lesion at the greater tuberosity using bone void filler in combination with a double row anchor reconstruction technique. Despite disadvantageous position and size of the cyst, using this technique the footprint can be restored by obtaining an anatomical position of the supraspinatus tendon. The application range of this technique is not limited to defined bony defects and presents a promising novel surgical approach. Level of evidence V.

Kyphoplasty Versus Vertebroplasty

Retrospective comparative analysis. We analyzed kyphosis correction, vertebral height restoration, and bone cement leakage in patients treated by vertebroplasty (VP) and kyphoplasty (KP) to compare the effectiveness of VP and KP for the treatment of osteoporotic vertebral compression fractures. Superior results have been reported for the use of KP for kyphotic deformity correction and collapsed vertebral height restoration. However, there are no previous comparative reports comparing the efficacy of KP versus VP according to the shapes of fractured vertebrae. A total of 103 patients underwent either VP (n=58) or KP (n=45) for treatment of osteoporotic vertebral compression fracture between October 2006 and September 2009. We organized the patients into 6 groups according to treatment method and fracture type: VP (wedge-shaped), VP (V-shaped), VP (flat-shaped), KP (wedge-shaped), KP (V-shaped), and KP (flat-shaped). Comparisons were performed for kyphosis correction, vertebral height restoration, and cement leakage between VP and KP groups. KP was more effective than VP, especially for middle column height restoration and bone cement leakage prevention, for all fracture types (P value <0.05). In addition, KP was more effective in anterior height restoration and kyphosis correction in both flat and wedge-shape fractures (P value <0.05). However, posterior column vertebral height was not restored in either the KP group or the VP group. The clinical outcomes did not differ between the 2 groups (P value >0.05). KP has a significant advantage over VP in terms of kyphosis correction, vertebral height restoration, and cement leakage prevention. KP has an obvious advantage in terms of middle vertebral height restoration and cement leakage prevention, especially for V-shape compression fractures.

Strontium- and magnesium-enriched biomimeticβ-TCP macrospheres with potential for bone tissue morphogenesis

During the last two decades, biogenic mineral ions have become important additives in treatments for bone regeneration and repair. Prominent among these is strontium, which is a potent suppressor of osteoclast bone resorption. Another is magnesium, which has a key influence in mineralization processes. The shells of benthic foraminiferans, hydrothermally converted into β-TCP, have been shown to effectively release a number of bone-promoting drugs at clinically relevant levels. In this study we characterized the effects of converted foraminiferan calcium dissolution and the concomitant release profile of intrinsic strontium and magnesium. We tested the effects of strontium- and magnesium-enriched macrospheres on human osteoblast (SaOS-2) and monocytoid (U937) cell lines, which can be induced to express equivalent phagocytic activities to osteoclasts. On dissolution in a biomimetic physiological solution, the macrospheres released biologically significant quantities of calcium and phosphate ions in the first 18 days. At 3 days, during which biogenic mineral ions are released, the number of U937 osteoclast-like monocyte cells decreased, while 4 days later the osteoblast cell number increased. These results show that strontium and magnesium naturally enriched macrospheres are capable of altering the metabolic activities of the cells regulating bone homeostasis. These unique macrospheres are natural origin bone void filler particles that resorb, and release physiologically significant levels of incorporated strontium, magnesium and calcium, which together make a uniquely multifunctional in situ remedy for bone regeneration and repair and the treatment of bone-wasting diseases.

The osteogenic differentiation of human bone marrow MSCs on HUVEC-derived ECM and β-TCP scaffold

Extracellular matrix (ECM) serves a key role in cell migration, attachment, and cell development. Here we report that ECM derived from human umbilical vein endothelial cells (HUVEC) promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSC). We first produced an HUVEC-derived ECM on a three-dimensional (3D) beta-tricalcium phosphate (β-TCP) scaffold by HUVEC seeding, incubation, and decellularization. The HUVEC-derived ECM was then characterized by SEM, FTIR, XPS, and immunofluorescence staining. The effect of HUVEC-derived ECM-containing β-TCP scaffold on hMSC osteogenic differentiation was subsequently examined. SEM images indicate a dense matrix layer deposited on the surface of struts and pore walls. FTIR and XPS measurements show the presence of new functional groups (amide and hydroxyl groups) and elements (C and N) in the ECM/β-TCP scaffold when compared to the β-TCP scaffold alone. Immunofluorescence images indicate that high levels of fibronectin and collagen IV and low level of laminin were present on the scaffold. ECM-containing β-TCP scaffolds significantly increased alkaline phosphatase (ALP) specific activity and up-regulated expression of osteogenesis-related genes such as runx2, alkaline phosphatase, osteopontin and osteocalcin in hMSC, compared to β-TCP scaffolds alone. This increased effect was due to the activation of MAPK/ERK signaling pathway since disruption of this pathway using an ERK inhibitor PD98059 results in down-regulation of these osteogenic genes. Cell-derived ECM-containing calcium phosphate scaffolds is a promising osteogenic-promoting bone void filler in bone tissue regeneration.

Adjuncts in posterior lumbar spine fusion: comparison of complications and efficacy

The purpose of this study was to define the efficacy of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) and Demineralized Bone Matrix (DBM) compared to autograft in posterior lumbar spine fusion by comparing complication rates. During a 7-year period (2003-2009), all patients undergoing posterior lumbar fusion were retrospectively evaluated within a large orthopedic surgery private practice. Patient demographics, comorbidities, number of levels, type of surgery, and types of bone void filler and osteobiologics were analyzed. Complications were defined as reoperation secondary to failed symptomatic fusion, hyper-reaction with fluid collections, bone overgrowth, and infections. 1,398 patients were evaluated with 41.1% males and 58.9% females. Mean age was 60years and BMI 30.6kg/m². Patients were subdivided in treatment groups: rhBMP-2, 947 (67.7%), DBM 306 (21.9%), and autograft 145 (10.4%). The overall infection rate was 2.1%. No significant differences were found between the three groups. The incidence of seroma formation was higher in the BMP group (3.2%) than in the DBM or autograft group (2.0 and 1.4%, respectively) but this was not significant (p=0.286 and p=0.245, respectively). 103 patients (7.4%) underwent redo surgery for clinically significant nonunion. We found significantly fewer nonunions (4.3%) in the rhBMP-2 group (p<0.001) compared to the DBM or autograft group (13.1 and 15.2%, respectively). ICBG is the gold standard. DBM leads to comparable fusion rates and does not increase infection or seroma formation. rhBMP-2 supplementation instead of ICBG or bone marrow aspirate results in higher fusion rates compared to autograft alone or autograft plus DBM.

A Semi-Autonomous Model of Endochondral Ossification for Developmental Tissue Engineering

Bone tissue engineering is currently undergoing a paradigm shift regarding the concepts used to develop cell-based therapies for skeletal repair. In place of the "trial and error" approach, researchers aim at developing cellular concepts that mirror developmental and postnatal processes. Herein, we describe a model for in vivo endochondral remodeling of an in vitro derived cartilaginous intermediate and its applicability to bone engineering. In vitro differentiation of the continuous cell line, ATDC5, in pellet culture was enhanced in a medium containing ascorbic acid, insulin-transferrin-selenium, dexamethasone, and transforming growth factor β1, when compared with other tested preparations. This differentiation was characterized by the elevated expression of Collagen type II and X along with glycosaminoglycan (GAG) accumulation and the onset of hypertrophy. On combination with NuOss™, a clinically used bone void filler, and implantation in nude mice, the differentiated pellets further matured into GAG rich cartilaginous intermediates after 4 weeks. This was subsequently partially remodeled into osteocalcin-positive bone tissue after 8 weeks without further external manipulation, indicating the semi-autonomous nature of this implant. Mineralized tissue along with active osteoclast resorption and neo-angiogenesis was apparent throughout the implant. The bone volume was approximately eightfold higher (10.70%±0.99%) when using a cartilaginous intermediate (based on differentiated cell pellets) than when observed with cell-seeded scaffolds (1.19%±0.24% and 1.48%±0.35%), in both a differentiated and an undifferentiated state. This study highlights the potential of endochondral strategies for bone tissue engineering and allows the identification of the key cellular parameters for this process.

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion

Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

Biocompatibility and resorption of a radiopaque premixed calcium phosphate cement

Calcium phosphate cements (CPC) are used as bone void filler in various orthopedic indications; however, there are some major drawbacks regarding mixing, transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a premixed calcium phosphate cement (pCPC), some of these difficulties can be overcome. In the treatment of vertebral fractures the handling characteristics need to be excellent including a high radio-opacity for optimal control during injection. The aim of this study is to evaluate a radiopaque pCPC regarding its resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were injected into a Ø 4-mm drilled femur defect in rabbits. The rabbits were sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated using histology, electron microscopy, and immunohistochemical analysis. Signs of inflammation were evaluated both locally and systemically. The results showed a higher bone formation in the pCPC compared to the water-based CPC after 2 weeks by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in both groups. Both materials were considered to have a high biocompatibility since no marked immunological response was induced and extensive bone ingrowth was observed. The conclusion from the study was that pCPC with ZrO(2) radiopacifier is a promising alternative regarding bone replacement material and may be suggested for treatment of, for example, vertebral fractures based on its high biocompatibility, fast bone ingrowth, and good handling properties.

Osteoconductivity and osteoinductivity of NanoFUSE® DBM

Bone graft substitutes have become an essential component in a number of orthopedic applications. Autologous bone has long been the gold standard for bone void fillers. However, the limited supply and morbidity associated with using autologous graft material has led to the development of many different bone graft substitutes. Allogeneic demineralized bone matrix (DBM) has been used extensively to supplement autograft bone because of its inherent osteoconductive and osteoinductive properties. Synthetic and natural bone graft substitutes that do not contain growth factors are considered to be osteoconductive only. Bioactive glass has been shown to facilitate graft containment at the operative site as well as activate cellular osteogenesis. In the present study, we present the results of a comprehensive in vitro and in vivo characterization of a combination of allogeneic human bone and bioactive glass bone void filler, NanoFUSE(®) DBM. NanoFUSE(®) DBM is shown to be biocompatible in a number of different assays and has been cleared by the FDA for use in bone filling indications. Data are presented showing the ability of the material to support cell attachment and proliferation on the material thereby demonstrating the osteoconductive nature of the material. NanoFUSE(®) DBM was also shown to be osteoinductive in the mouse thigh muscle model. These data demonstrate that the DBM and bioactive glass combination, NanoFUSE(®) DBM, could be an effective bone graft substitute.

Can mesenchymal stem cell survive in hydroxyapatite sulphate?

Background: Many studies have reported the role of Mesenchymal Stem Cells (MSC) in treating fractures. In case with bone defect, fracture healing needs not only osteogenic but also osteoconductive component (scaffold). Hydroxyapatite calcium sulphate (HA-CaSO4) being widely used as bone void filler, may serve as scaffold for MSC. However, the effect of this scaffold to the viability of MSC has not been evaluated before.Methods: MSC were isolated from the iliac marrow of a Giant Flamish rabbit, and expanded in DMEM using histogradient density. After one week, they were sub-cultured in a 25cc TC flask (passage 1) and have the medium replaced every 3 days. During the subculture, we embedded a HA-CaSO4 pellet into the flask. The cells were evaluated under inverted microscope at a weekly interval.Results: At the first week, MSC are difficult to be identified in microscope due to the large number of HA-CaSO4 crystals. By the third week however MSC have grown and the HA-CaSO4 crystals can readily be washed off by medium replacement. By the fourth weeks, MSC can be still seen on microscope.Conclusion: HA-CaSO4 could serve as a good scaffold due to its pellet shape and easily absorbed, thus providing revascularization which is essential for bone healing.In addition, HA-CaSO4 does not interfere with MSC survival. (Med J Indones 2012;21:8-12)Keywords: Fracture healing, Hydroxyapatite Calcium Sulphate (HA-CaSO4), Mesenchymal Stem Cells (MSC)

A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells

The response of osteoprogenitors to calcium (Ca2+) is of primary interest for both normal bone homeostasis and the clinical field of bone regeneration. The latter makes use of calcium phosphate-based bone void fillers to heal bone defects, but it is currently not known how Ca2+ released from these ceramic materials influences cells in situ. Here, we have created an in vitro environment with high extracellular Ca2+ concentration and investigated the response of human bone marrow-derived mesenchymal stromal cells (hMSCs) to it. Ca2+ enhanced proliferation and morphological changes in hMSCs. Moreover, the expression of osteogenic genes is highly increased. A 3-fold up-regulation of BMP-2 is observed after only 6h and pharmaceutical interference with a number of proteins involved in Ca2+ sensing showed that not the calcium sensing receptor, but rather type L voltage-gated calcium channels are involved in mediating the signaling pathway between extracellular Ca2+ and BMP-2 expression. MEK1/2 activity is essential for the effect of Ca2+ and using microarray analysis, we have identified c-Fos as an early Ca2+ response gene. We have demonstrated that hMSC osteogenesis can be induced via extracellular Ca2+, a simple and economic way of priming hMSCs for bone tissue engineering applications.

Nanocrystalline hydroxyapatite facilitates bone apposition to polymethylmethacrylate: Histological investigation using a sheep model

Polymethylmethacrylate (PMMA) is the most commonly used bone void filler for vertebral augmentation in osteoporotic fracture. It provides mechanical stability and immediate pain relief; however, PMMA is not osteointegrated and is separated from the surrounding bone tissue by a thin fibrous layer. The aim of this study was to investigate the effect of nanocrystalline hydroxyapatite (HA) on osteointegration of PMMA in a sheep model. A composite material, consisting of PMMA and nanocrystalline HA (70:30, v/v), was implanted in one distal femur, with pure PMMA in the other femur as a control. Three and 6 months after implantation, the distal femora were histologically investigated. All composite implants exhibited a tight junction to the surrounding bone tissue, with minimal bone ingrowth into the outer surface of the implant. In comparison, with use of the control implants, we observed an overall bone resorption around pure PMMA, with fibrous connective tissue encapsulating the implant. These results suggest that nanocrystalline HA enables osteointegration of PMMA in bone tissue, which might alter the biomechanical characteristics of the osteoporotic vertebral body after augmentation.

Comparative clinical results of vertebroplasty using jamshidi® needle and bone void filler for acute vertebral compression fractures.

ObjectivePercutaneous vertebroplasty (PVP) is an effective treatment modality for management of osteoporotic compression fracture. However physicians sometimes have problems of high pressure in cement delivery and cement leakage when using Jamshidi® needle (JN). Bone void filler (BVF) has larger lumen which may possibly diminish these problems. This study aims to compare the radiologic and clinical outcome of JN and BVF for PVP.MethodsOne hundred twenty-eight patients were treated with PVP for osteoporotic vertebral compression fracture (VCF) where 46 patients underwent PVP with JN needle and 82 patients with BVF. Radiologic outcome such as kyphotic angle and vertebral body height (VBH) and clinical outcome such as visual analog scale (VAS) scores were measured after treatment in both groups.ResultsIn JN PVP group, mean of 3.26 cc of polymethylmethacrylate (PMMA) were injected and 4.07 cc in BVF PVP group (p<0.001). For radiologic outcome, no significant difference in kyphotic angle reduction was observed between two groups. Cement leakage developed in 6 patients using JN PVP group and 2 patients using BVF group (p=0.025). No significant difference in improvement of VAS score was observed between JN and BVF PVP groups (p=0.43).ConclusionFor the treatment of osteoporotic VCF, usage of BVF for PVP may increase injected volume of cement, easily control the depth and direction of PMMA which may reduce cement leakage. However, improvement of VAS score did not show difference between two groups. Usage of BVF for PVP may be an alternative to JN PVP in selected cases.

THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING

The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).

Changes in Neuroforaminal Dimensions with Two-Level Axial Lumbar Interbody Fusion at L4-S1 with Graduated Distraction through the Implant

PURPOSE: The goal of this study was to evaluate the number of complications requiring reoperation for symptomatic failed fusion and hyper responsive compressive fluid collections. STUDY DESIGN/SETTING: Retrospective cohort study/one large orthopaedic surgery private practice associated with a tertiary referral spine center. PATIENT SAMPLE: 1158. OUTCOMEMEASURES: Complications related to rhBMP were defined as reoperation secondary to failed symptomatic fusion, hyper reaction resulting in compressive fluid collections, hyper formation of bone resulting in neural compression, and infections. METHODS: During a 7-year period of time (2002–2009), all patients undergoing lumbar posterolateral fusion utilizing of rhBMP-2 (INFUSE) were retrospectively evaluated within a large orthopaedic surgery private practice. Patient demographics, comorbidities, number of levels, and types of bone void filler (BVF) were analyzed. Complications related to rhBMP were defined as reoperation secondary to failed symptomatic fusion, hyper reaction resulting in compressive fluid collections, hyper formation of bone resulting in neural compression, and infections. RESULTS: 1158 consecutive patients were evaluated with 468 (40.4%) males and 690 (59.6%) females. Average age was 59.2 yo and BMI was 30.7 kg/m. Number of levels fused was: 1 (414, 35.8%), 2 (469, 40.5%), 3 (162, 14.0%), 4 (70, 6.0%), 5 (19, 1.6%), 6 (11, 0.9%), 7 (7, 0.6%), 8 (4, 0.3%), and 9 (2, 0.2%). Complications including add on stenosis requiring reoperation were 117/1158 (10.1%): Seroma with acute neural compression 32 (2.8%), excess bone formation with delayed neural compression 4 (0.3%), infection requiring debridement 26 (2.2%), and symptomatic nonunion requiring redo fusion and instrumentation 41 (3.5%). Nonunion was not related to smoking, number of levels fused, or age. There was an increased risk for nonunion in male patients and patients with previous BMP exposition. All nonunions were successfully treated with redo surgical instrumentation and rhBMP application. Seroma formation was not associated with interbody fusion, gender, BMI or comorbidities and was associated with acute exacerbation of radicular pain and transient neural involvement of varying degrees. The incidence of seroma formation was significantly higher in patients with higher doses of rhBMP-2 (p5.050) and especially in patients with more than 12 mg rhBMP-2 (c50.025). Bone reformation at the laminectomy and foraminotomy sites occurred in a delayed fashion associated with a solid union, progressive worsening of radicular pain, and were successfully treated with repeat neural decompression only. CONCLUSIONS: rhBMP-2 is a reliable adjunct for bone induction in posterolateral lumbar fusions. Complication rates using rhBMP-2 are low and do not exceed complication rates using iliac crest bone graft. A higher rate of seroma formation and infection occurs with increasing rhBMP-2 dose. Therefore, further studies concerning rhBMP-2 dosage are warranted. FDA DEVICE/DRUG STATUS: rhBMP-2: Investigational/Not approved.

Calcium Phosphate Bone Cement (CPBC): Development, Commercialization and Future Challenges

The first generation of synthetic bone substitute materials, hydroxyapatite (or HA), was initially investigated as a “non self-hardening” biomaterial for remodeling of bone defects. CPBCs concepts were used as a platform to initiate a second generation of injectable, self-hardening cement. The variety of CPBC’s chemical composition leads to a better understanding of their mechanism of reaction and their proposed classification: acid-base, mono-component and hydrolysable. After hydration, mixing, and full chemical reaction, these cements have the ability to precipitate different end products (e.g. HA, calcium deficient apatite, carbonated apatite, brushite, etc.). In fact, the initial idea of having higher mechanical performance (&gt;50 MPa in compression) for a bone void filler application was abandoned and has led to a greater focus on cement fast-hardening (&lt;15 min), higher total porosity (&gt;60%), extended performance of injectability (8 to 22 G), fast resorbability (&lt; 2 years) and user-friendliness for the clinicians. A new CPBC combination (cement plus additives) has particularly improved rheological and biointegrity performance. A hybrid of CPBC-DBM (Demineralized Bone Matrix) has also added an osteoinductivity performance to the initial osteoconductive CPBC.This paper will propose a comparison of the chemical composition, reaction, and performance characteristics of major commercially available CPBC products. Furthermore, it will describe today’s surgeon’s CPBC needs as bone substitute materials for different clinical applications. Finally, we will discuss what we learned so far, how we can resolve several clinical impacts &amp; product recall, and how we believe CPBC designers can meet development challenges, and users’ specific requirements.

Fracture of the Talus as a Complication of Subtalar Arthroereisis

Subtalar joint arthroereisis remains a popular procedure for a flexible flatfoot deformity. Potential complications of the procedure have been discussed in published reports and are often believed to have resulted from shortcomings related to the mechanical properties of the biomaterial, implant size, and/or implant placement. In the present report, we describe the case of a talar neck fracture with migration of the implant after subtalar joint arthroereisis performed 10 years earlier. The 19-year-old patient was treated with implant removal and open reduction internal fixation and bone void filler and recovered unremarkably thereafter.