Silicate-substituted Calcium Phosphate Research Articles

Fabrication and in vitro evaluation of 3D printed porous silicate substituted calcium phosphate scaffolds for bone tissue engineering.

Silicate-substituted calcium phosphate (Si-CaP) ceramics, alternative materials for autogenous bone grafting, exhibit excellent osteoinductivity, osteoconductivity, biocompatibility, and biodegradability; thus, they have been widely used for treating bone defects. However, the limited control over the spatial structure and weak mechanical properties of conventional Si-CaP ceramics hinder their wide application. Here, we used digital light processing (DLP) printing technology to fabricate a novel porous 3D printed Si-CaP scaffold to enhance the scaffold properties. Scanning electron microscopy, compression tests, and computational fluid dynamics simulations of the 3D printed Si-CaP scaffolds revealed a uniform spatial structure, appropriate mechanical properties, and effective interior permeability. Furthermore, compared to Si-CaP groups, 3D printed Si-CaP groups exhibited sustained release of silicon (Si), calcium (Ca), and phosphorus (P) ions. Furthermore, 3D printed Si-CaP groups had more comprehensive and persistent osteogenic effects due to increased osteogenic factor expression and calcium deposition. Our results show that the 3D printed Si-CaP scaffold successfully improved bone marrow mesenchymal stem cells(BMSCs) adhesion, proliferation, and osteogenic differentiation and possessed a distinct apatite mineralization ability. Overall, with the help of DLP printing technology, Si-CaP ceramic materials facilitate the fabrication of ideal bone tissue engineering scaffolds with essential elements, providing a promising approach for bone regeneration.

Co-transplantation of Wharton's jelly mesenchymal stem cell-derived osteoblasts with differentiated endothelial cells does not stimulate blood vessel and osteoid formation in nude mice models.

A major challenge in bone tissue engineering is the lack of post-implantation vascular growth into biomaterials. In the skeletal system, blood vessel growth appears to be coupled to osteogenesis-suggesting the existence of molecular crosstalk between endothelial cells (ECs) and osteoblastic cells. The present study (performed in two murine ectopic models) was designed to determine whether co-transplantation of human Wharton's jelly mesenchymal stem cell-derived osteoblasts (WJMSC-OBs) and human differentiated ECs enhances bone regeneration and stimulates angiogenesis, relative to the seeding of WJMSC-OBs alone. Human WJMSC-OBs and human ECs were loaded into a silicate-substituted calcium phosphate (SiCaP) scaffold and then ectopically implanted at subcutaneous or intramuscular sites in nude mice. At both subcutaneous and intramuscular implantation sites, we observed ectopic bone formation and osteoids composed of host cells when WJMSC-OBs were seeded into the scaffold. However, the addition of ECs was associated with a lower level of osteogenesis, and we did not observe stimulation of blood vessel ingrowth. in vitro studies demonstrated that WJMSC-OBs lost their ability to secrete vascular endothelial growth factor and stromal cell-derived factor 1-including when ECs were present. In these two murine ectopic models, our cell-matrix environment combination did not seem to be optimal for inducing vascularized bone reconstruction.

Autologous Bone Graft Versus Silicate-Substituted Calcium Phosphate in the Treatment of Tunnel Defects in 2-Stage Revision Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized Controlled Study With a Minimum Follow-up of 2 Years

To compare and evaluate knee laxity and functional outcomes between autologous bone graft and silicate-substituted calcium phosphate (Si-CaP) in the treatment of tunnel defects in 2-stage revision anterior cruciate ligament reconstruction (ACLR). This prospective, randomized controlled trial was conducted between 2012 and 2015 with a total of 40 patients who underwent 2-stage revision ACLR. The tunnels were filled with autologous iliac crest cancellous bone graft in 20 patients (control group) and with Si-CaP in the other 20 patients (intervention group). After a minimum follow-up period of 2years, functional outcomes were assessed by KT-1000 arthrometry (side-to-side [STS] difference), the Tegner score, the Lysholm score, and the International Knee Documentation Committee score. A total of 37 patients (follow-up rate, 92.5%) with an average age of 31years were followed up for 3.4years (range, 2.2-5.5years). The KT-1000 measurement did not show any STS difference between the bone graft group (0.9 ±1.5mm) and the Si-CaP group (0.7 ± 2.0mm)(P= .731). One patient in the intervention group (5%) had an STS difference greater than 5mm. Both groups showed significant improvements in the Tegner score, Lysholm score, and International Knee Documentation Committee score from preoperative assessment to final follow-up (P ≤ .002), without any difference between the 2 groups (P ≥ .396). Complications requiring revision occurred in 4 control patients (22%) and in 2 patients in the intervention group (11%) (P= .660). No complications in relation to Si-CaP were observed. Equivalent knee laxity and clinical function outcomes were noted 3years after surgery in both groups of patients. Si-CaP bone substitute is therefore a safe alternative to autologous bone graft for 2-stage ACLR. Level I, prospective, randomized controlled clinical trial.

Two-Stage Revision Anterior Cruciate Ligament Reconstruction Using Silicate-Substituted Calcium Phosphate

Revision surgery after failed primary anterior cruciate ligament reconstruction is technically demanding. In cases in which the tunnels of the primary anterior cruciate ligament reconstruction are widened to greater than 10 mm and/or are incorrectly positioned, a 2-stage procedure enables restoration of bone stock and thus free placement of the tunnels during the revision. The gold standard for tunnel augmentation is an autologous iliac crest cancellous bone graft. However, harvesting the graft is associated with high morbidity. This article describes an alternative method for managing bone deficiencies using the synthetic bone graft substitute silicate-substituted calcium phosphate.

Lumbar interbody fusion rates with 3D-printed lamellar titanium cages using a silicate-substituted calcium phosphate bone graft

The synthetic bone graft material, silicate-substituted calcium phosphate (SiCaP), has been successfully used in spinal fusion surgery. The efficacy of SiCaP-packed 3D-printed lamellar titanium cages used in transforaminal lumbar interbody fusion (TLIF) and lateral lumbar interbody fusion (LLIF) requires investigation. This study evaluated the efficacy of this combination in TLIF and LLIF surgeries treating adult spinal deformities and degenerative disorders. We retrospectively analysed a consecutive case series of 93 adult patients with lumbar degenerative disease or deformity requiring interbody cages who underwent TLIF or LLIF surgery with SiCaP-packed 3D-printed lamellar titanium cages, performed by a single lead surgeon. The primary endpoint was solid fusion 12 months after surgery, assessed using computed tomography. Secondary endpoints were patient-reported outcomes; EuroQOL five dimensions (EQ-5D), visual analogue scale (VAS) for pain (EQ-5D VAS), VAS pain scores for leg and back, and Oswestry disability index (ODI). Complications were recorded. Computed tomography revealed solid fusion in 92/93 (98.9%) patients with good cage integration at the vertebral body interface and no evidence of screw loosening. Patient-reported outcomes significantly improved for all parameters 1 year post-operation. Mean VAS significantly declined 1 year following TLIF surgery (back: −5.5; leg: −6.7) and following LLIF surgery (back: −5.9; leg: −6.9). Mean ODI declined 1 year following TLIF surgery (−43.0) from crippled to minimal disability and following LLIF surgery (−41.2) from severe to minimal disability. SiCaP-packed 3D-printed lamellar titanium cages provided excellent rates of solid fusion in TLIF and LLIF surgeries with notable improvements in patient-reported outcomes.

A carboxymethyl cellulose bone graft carrier delays early bone healing in an ovine model.

A limitation in the use of calcium phosphate (CaP) is that in its raw form, it comprises blocks or granules, which are limited in their utility for orthopedic surgery and a number of commercial bone grafts are supplied within an aqueous based carboxymethyl cellulose (CMC) putty. Our hypothesis was that CMC combined with a porous silicate-substituted CaP (SiCaP) scaffold would have no negative effect on bone formation after implantation in an ovine femoral condyle. Defects were either (a) empty or filled with (b) SiCaP granules, (c) CMC-SiCaP Putty or (d) a SiCaP press-fit dry block. Scaffolds were identical in composition and remained in vivo for 4, 8, and 12 weeks. Bone apposition rates, bone area, percentage of bone-implant contact and graft area were quantified. At 4 and 8 weeks, significantly more new bone and percentage of bone-implant contact was measured within granules when compared with both putty and block scaffolds. At 12 weeks, significantly increased bone was measured for the granules when compared with blocks and no significant difference was found when the granules and putty scaffolds were compared. Results showed the disadvantageous effect that CMC may have on early bone growth and that granules increased new bone formation when compared with a press-fit block composed of the same material.

Evaluation of an increased strut porosity silicate-substituted calcium phosphate, SiCaP\xa0EP, as a synthetic bone graft substitute in spinal fusion surgery: a prospective, open-label study

PurposeSilicate-substituted calcium phosphate-enhanced porosity (SiCaP EP, Inductigraft™, Altapore) is a synthetic bone graft material with enhanced strut porosity of 31–47%. SiCaP EP remains to be fully clinically evaluated in patients undergoing instrumented posterolateral fusion (PLF) surgery. We conducted a prospective, open-label, non-randomised, multicentre clinical study to evaluate efficacy of SiCaP EP as bone grafting material in PLF surgery with instrumentation for treatment of spinal disorders.MethodsPatients with degenerative disc disease, spondylolisthesis or spinal stenosis underwent PLF surgery with SiCaP EP. The primary endpoint was evaluated in the per protocol population (N = 102) as solid fusion at postoperative month 12 assessed using computed tomography scans, with motion assessed using flexion–extension radiographs. Clinical outcomes included the Oswestry Disability Index, 36-item short-form health survey for quality-of-life, visual analog scale for pain scores and neurological assessments. Adverse events were recorded.ResultsSuccessful fusion was achieved in 59/89 (66.3%) patients at month 6, 88/102 patients (86.3%) at month 12 (primary endpoint) and 87/96 (90.6%) patients at month 24. Disability and pain reduced following surgery. Quality-of-life improved and neurological function was maintained postoperatively. Forty-three (33.3%) of the 129 patients who underwent surgery experienced adverse events; back pain was most frequent (n = 10); nine and 14 patients experienced serious adverse events judged related to device and procedure, respectively.ConclusionsEnhanced strut porosity SiCaP EP provided high (month 12: 86.3%) spinal fusion success rates in PLF surgery. Fusion success was associated with improved clinical outcomes in patients within 12 months, relative to baseline.ClinicalTrials.gov identifierNCT01452022Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Surface mediated non-viral gene transfection on titanium substrates using polymer electrolyte and nanostructured silicate substituted calcium phosphate pDNA (NanoSiCaPs) composites

Exploiting gene delivery from the surfaces of bio-functionalized implants is a unique strategy to facilitate tissue regeneration and integration. However, it has been challenging, due to the difficulty for incorporation and delivey of sufficient payloads of plasmid DNA (pDNA) to cells from the implant surface allowing efficient gene expression. Herein, we describe a novel and simple coating approach using nanostructured silicate substituted calcium phosphate pDNA complexes termed as NanoSiCaPs, that preferentially adsorb onto titanium (Ti) substrates coated with poly (diallyldimethylammonium chloride) (PDADMAC). The Ti-polyelectrolyte NanoSiCaPs assemblies aptly called PNA, deliver pDNA to MC3T3-E1 cells (pre-osteoblast cell line), induce protein production, without eliciting any cytotoxicity, while simultaneously encouraging cell attachment on the substrate.

Radiographic and Clinical Outcome of Silicate-substituted Calcium Phosphate (Si-CaP) Ceramic Bone Graft in Spinal Fusion Procedures.

Retrospective cohort study. To evaluate the radiographic and clinical outcome of silicate-substituted calcium phosphate (Si-CaP), utilized as a graft substance in spinal fusion procedures. Specific properties of Si-CaP provide the graft with negative surface charge that can result in a positive effect on the osteoblast activity and neovascularization of the bone. This study included those patients who underwent spinal fusion procedures between 2007 and 2011 in which Si-CaP was used as the only bone graft substance. Fusion was evaluated on follow-up CT scans. Clinical outcome was assessed using Oswestry Disability Index, Neck Disability Index, and the visual analogue scale (VAS) for back, leg, neck, and arm pain. A total of 234 patients (516 spinal fusion levels) were studied. Surgical procedures consisted of 57 transforaminal lumbar interbody fusion, 49 anterior cervical discectomy and fusion, 44 extreme lateral interbody fusion, 30 posterior cervical fusions, 19 thoracic fusion surgeries, 17 axial lumbar interbody fusions, 16 combined anterior and posterior cervical fusions, and 2 anterior lumbar interbody fusion. At a mean radiographic follow-up of 14.2±4.3 months, fusion was found to be present in 82.9% of patients and 86.8% of levels. The highest fusion rate was observed in the cervical region. At the latest clinical follow-up of 21.7±14.2 months, all clinical outcome parameters showed significant improvement. The Oswestry Disability Index improved from 45.6 to 13.3 points, Neck Disability Index from 40.6 to 29.3, VAS back from 6.1 to 3.5, VAS leg from 5.6 to 2.4, VAS neck from 4.7 to 2.7, and VAS arm from 4.1 to 1.7. Of 7 cases with secondary surgical procedure at the index level, the indication for surgery was nonunion in 3 patients. Si-CaP is an effective bone graft substitute. At the latest follow-up, favorable radiographic and clinical outcome was observed in the majority of patients. Level-III.

Bone Incorporation of Silicate-Substituted Calcium Phosphate in 2-Stage Revision Anterior Cruciate Ligament Reconstruction: A Histologic and Radiographic Study

To evaluate the histologic and radiographic outcomes of using silicate-substituted calcium phosphate (Si-CaP) as bone graft substitute for the augmentation of tunnel defects in 2-stage revision anterior cruciate ligament (ACL) reconstruction. Forty patients undergoing 2-stage revision ACL reconstruction were included in a prospective, randomized controlled clinical trial between 2012 and 2015. The inclusion criteria were tunnel diameter of the tibial and/or femoral tunnel of 10mm or greater after failed ACL reconstruction. Twenty patients received autologous bone from the iliac crest and 20 patients received Si-CaP as a bone graft substitute for tunnel grafting at the first-stage procedure. Punch biopsy specimens of the augmented tunnels were taken at the second-stage procedure, and histologic examination included quantitative analysis of the area of immature bone formation, lamellar bone, and bone marrow. Radiographic analysis included determination of the filling rates of the tunnels on postoperative computed tomography scans. Forty patients with a mean age of 32years (standard deviation [SD], 11.0years) were analyzed. Histologic examination of the tunnels filled with Si-CaP showed that 15% (SD, 14%) of the area was covered with immature bone formation, 41% (SD, 10%) with well-organized lamellar bone, and 44% (SD, 8%) with bone marrow. In the control group (autologous bone), 58% (SD, 3%) of the area was covered with well-organized lamellar bone and 42% (SD, 3%) with bone marrow. Quantitative evaluation of the postoperative computed tomography scans showed a trend of better filling rates in patients with Si-CaP for the tibial tunnel (86% [SD, 17%] vs 78% [SD, 14%]; P= .131). Intraoperatively, Si-CaP was completely integrated into the original bone tunnel providing good stability for tunnel placement and tendon graft fixation comparable to autologous bone. Si-CaP as bone graft substitute for tunnel augmentation in 2-stage revision ACL reconstruction shows good histologic, radiographic, and intraoperative integration comparable to autologous bone. Level I, prospective randomized controlled trial.

Nanostructured silicate substituted calcium phosphate (NanoSiCaPs) nanoparticles — Efficient calcium phosphate based non-viral gene delivery systems

Nanostructured ceramic particles, particularly, nanoparticles of calcium phosphate (CaP) remain an attractive option among the various types of non-viral gene delivery vectors studied because of their safety, biocompatibility, biodegradability, and ease of handling as well as their adsorptive capacity for DNA. We have accordingly developed an enhanced version of nanostructured calcium phosphates (NanoCaPs), by substituting known amounts of silicate for phosphate in the hydroxyapatite (HA) lattice (NanoSiCaPs). Results indicate that in addition to the excellent transfection levels exhibited by un-substituted NanoCaPs alone in vitro, an additional 20–50% increase in transfection is observed for NanoCaPs containing 8.3–50mol% silicate aptly called NanoSiCaPs, owing to its rapid dissolution properties enabling nanoparticles escaping the lysosomal degradation. However, high silicate substitution (>50mol%) resulted in a drastic decline in transfection as the synthesized NanoCaPs deviated far from the characteristic hydroxyapatite phase formed as evidenced by the materials characterization results.

Retraction. Prospective, randomized, controlled trial of silicate-substituted calcium phosphate versus rhBMP-2 in a minimally invasive transforaminal lumbar interbody fusion. Spine (Phila Pa 1976) 2014. 39(3): 185-191. Nandyala, Sreeharsha V.; Marquez-Lara, Alejandro; Fineberg, Steven J.; Pelton, Miguel; Singh, Kern.

Retraction. Prospective, randomized, controlled trial of silicate-substituted calcium phosphate versus rhBMP-2 in a minimally invasive transforaminal lumbar interbody fusion. Spine (Phila Pa 1976) 2014. 39(3): 185-191. Nandyala, Sreeharsha V.; Marquez-Lara, Alejandro; Fineberg, Steven J.; Pelton, Miguel; Singh, Kern.

A carboxy-methyl cellulose carrier reduces bone formation within a silicate-substituted calcium phosphate scaffold

A carboxy-methyl cellulose carrier reduces bone formation within a silicate-substituted calcium phosphate scaffold

Efficacy of silicate-substituted calcium phosphate with enhanced strut porosity as a standalone bone graft substitute and autograft extender in an ovine distal femoral critical defect model.

A synthetic bone graft substitute consisting of silicate-substituted calcium phosphate with increased strut porosity (SiCaP EP) was evaluated in an ovine distal femoral critical sized metaphyseal defect as a standalone bone graft, as an autologous iliac crest bone graft (ICBG) extender (SiCaP EP/ICBG), and when mixed with bone marrow aspirate (SiCaP EP/BMA). Defects were evaluated after 4, 8, and 12 weeks with radiography, decalcified paraffin-embedded histopathology, non-decalcified resin-embedded histomorphometry, and mechanical indentation testing. All test groups exhibited excellent biocompatibility and osseous healing as evidenced by an initial mild inflammatory response followed by neovascularization, bone growth, and marrow infiltration throughout all SiCaP EP-treated defects. SiCaP EP/ICBG produced more bone at early time points, while all groups produced similar amounts of bone at later time points. SiCaP EP/ICBG likewise showed more favorable mechanical properties at early time points, but was equivalent to SiCaP EP and SiCaP EP/BMA at later time points. This study demonstrates that SiCaP EP is efficacious as a standalone bone graft substitute, mixed with BMA, and as an autograft extender.

Comparison of Silicate-Substituted Calcium Phosphate (Actifuse) with Recombinant Human Bone Morphogenetic Protein-2 (Infuse) in Posterolateral Instrumented Lumbar Fusion.

Study Design Randomized controlled trial. Objective The aim of this study was to assess the efficacy of the bone grafting substitute silicate-substituted calcium phosphate (SiCaP) compared with recombinant human bone morphogenetic protein 2 (rhBMP-2) and to evaluate the clinical outcomes over a period of 2 years. Methods Patients undergoing PLF surgery for DDD at a single center were recruited and randomized to one of two groups: SiCaP (n = 9) or rhBMP-2 (n = 10). One patient withdrew prior to randomization and another from the rhBMP-2 group after randomization. The radiologic and clinical outcomes were examined and compared. Fusion was assessed at 12 months with computed tomography and plain radiographs. Clinical outcomes were evaluated by recording measures of pain, quality of life, disability, and neurologic status from 6 weeks to 2 years postoperatively. Results In the SiCaP and rhBMP-2 groups, fusion was observed in 9/9 and 8/9 patients, respectively. Pain and disability scores were reduced and quality of life increased in both groups. Leg pain, disability, and satisfaction scores were similar between the groups at each postoperative point; however, back pain was less at 6 weeks and quality of life was higher at 6 months in the SiCaP group than the rhBMP-2 group. Conclusions SiCaP and rhBMP-2 were comparable in terms of achieving successful bone growth and fusion. Both groups achieved similar alleviation of pain and improved quality of life and neurologic, satisfaction, and return to work outcomes following PLF surgery.

Silicate-substituted calcium phosphate with enhanced strut porosity stimulates osteogenic differentiation of human mesenchymal stem cells.

While many synthetic ceramic bone graft substitutes (BGSs) have osteoconductive properties (e.g. provide a physical scaffold for osteointegration of surrounding bone tissue), certain BGSs are osteostimulative in that they actively upregulate mesenchymal stem cell proliferation and stimulate differentiation into osteoblast-like cells. The osteostimulative properties of silicate-substituted calcium phosphate with enhanced porosity (SiCaP EP) were evaluated in vitro with STRO-1+ immunoselected human bone marrow derived mesenchymal stem cells (HBMSCs). Osteostimulative materials (SiCaP) and Bioglass 45S5 (Bioglass) were also assessed as positive controls along with non-silicate substituted hydroxyapatite as a negative control. HBMSCs were also assessed on Thermanox discs cultured in basal and osteogenic media to determine when osteogenic differentiation could be significantly detected with this in vitro cell system. HBMSC viability and necrosis, total DNA content, alkaline phosphatase (ALP) expression, and osteocalcin expression were evaluated after 7, 14, 21, and 28 days. It was demonstrated that SiCaP EP is osteostimulative based on its propensity to support STRO-1+ HBMSC proliferation and ability to promote the differentiation of HBMSCs down the osteoblastic lineage from ALP-expressing, matrix-producing osteoblasts to Osteocalcin-producing pre-osteocytes without the presence of external osteogenic factors. SiCaP EP permitted greater HBMSC attachment as well as ALP and Osteocalcin expression than Bioglass which may be attributed to its microstructure and chemistry.

Prospective, Randomized, Controlled Trial of Silicate-Substituted Calcium Phosphate Versus rhBMP-2 in a Minimally Invasive Transforaminal Lumbar Interbody Fusion

Prospective, randomized, controlled trial. To compare arthrodesis rates between patients undergoing a primary single-level minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) with either Actifuse or recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical animal studies suggest that silicate-substituted calcium phosphate (Actifuse) bone graft substitute offers equivalent or an increased fusion rate compared with other graft enhancers/extenders and rhBMP-2. Fifty-two patients undergoing a single-level unilateral MIS TLIF were evenly randomized into 2 cohorts as follows: the Actifuse cohort received Actifuse combined with 5 mL of bone marrow aspirate (n = 26; 50%), whereas the rhBMP cohort received 4.2 mg of rhBMP-2 (n = 26; 50%). A pre hoc G*Power analysis yielded a sample size of n = 26 that was determined through a 2-tailed distribution calculation. Computed tomographic analysis was performed at 6 months and 1 year postoperatively. Pre- and postoperative visual analogue scale scores were obtained to assess the clinical outcomes. Arthrodesis was determined by 2 separate, blinded orthopedic surgeons and a board certified radiologist. At 1-year follow-up, 65% (17/26) of the Actifuse cohort and 92% (24/26) of the rhBMP-2 cohort demonstrated a radiographical arthrodesis (P = 0.01). In both study cohorts, the 1-year postoperative visual analogue scale scores significantly improved (P < 0.001). Pseudarthrosis rates at 1 year were 35.0% (9/26) and 7.7% (2/26) for the Actifuse and rhBMP-2 groups, respectively (P = 0.01, OR = 6.35, 95% CI = 1.22-33.1). A greater reoperation rate was noted in the Actifuse cohort (35.0%, 9/26) compared with the BMP-2 cohort (7.7%, 2/26; P = 0.01). One patient with BMP-2 also experienced symptomatic neuroforaminal bone growth (3.8%, n = 1/26). Silicate-substituted calcium phosphate was associated with a significantly lower rate of arthrodesis than rhBMP-2 in a MIS TLIF. The patients with pseudarthrosis in both cohorts were all clinically symptomatic with an unimproved visual analogue scale score. Additional analysis of Actifuse and other graft enhancers/extenders are needed prior to the utilization for an MIS TLIF. 2.

The effect of particle size on the osteointegration of injectable silicate-substituted calcium phosphate bone substitute materials.

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical-sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 μm in diameter (100 vol %). TG2 investigated a granule size of 250–500 μm (75 vol %), TG3 a granule size of 90–125 μm (75 vol %) and TG4 a granule size of 90–125 μm (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone-implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 μm in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects. © 2013 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 902–910, 2013

Silicate-substituted calcium phosphate as a bone graft substitute in surgery for adolescent idiopathic scoliosis

The purpose of this prospective clinical study is to evaluate the clinical and radiographic outcomes using a silicate-substituted calcium phosphate (Si-CaP) as a bone graft substitute in surgery for adolescent idiopathic scoliosis (AIS). In posterior corrective surgery for AIS, harvesting autologous bone from the iliac crest still represents the gold standard to augment the local bone graft though it is comparatively invasive and associated with donor site morbidity. Si-CaP enriched with bone marrow aspirate (BMA) might be an appropriate bone graft extender to overcome these difficulties. Eighteen female and three male patients with AIS who underwent corrective posterior instrumentation were observed clinically and radiographically for a minimum of 24 months. In all cases, 20-40 ml Si-CaP granules (ACTIFUSE) mixed with BMA from vertebral bodies was used to extend the local bone graft. Fusion was assessed by standardized conventional radiographs regarding loss of correction and implant failure. Clinical outcome was evaluated with use of the Scoliosis Research Society-22 patient Questionnaire (SRS-22) and a Visual Analog Scale (VAS) for back pain. Cobb angle of major curves averaged 63° preoperatively, 22° after surgery, and 24° at final follow-up, with a maximum loss of correction of 7° recorded after 4 months. No adverse effects related to the study material had been observed. In all patients, there was no evidence of implant failure, and formation of an increasingly densifying 'fusion mass' was visible, as assessed by conventional radiography. VAS score for back pain averaged 1.7 before surgery, 2.3 at discharge, and 1.5 at final follow-up. Outcome assessment using the SRS-22 revealed a significantly enhanced overall health-related quality of life (84 vs. 74 % before surgery; P = 0.0005) due to a significant improvement of the domains 'self image' (77 vs. 59 %; P = 0.0002) and 'pain' (88 vs. 80 %; P = 0.02). Patients' management satisfaction averaged 93 %. Si-CaP augmented with BMA from vertebral bodies seems to prove an effective, safe, and easy to handle bone graft extender in scoliosis surgery and thus a suitable alternative to bone harvesting procedures.

Silicate-Substituted Calcium Phosphate Ceramic Bone Graft Replacement for Spinal Fusion Procedures

Retrospective study. To assess the clinical and radiographical outcomes in spinal fusion procedures using silicate-substituted calcium phosphate (Si-CaP). Si-CaP is a newer-generation synthetic ceramic designed to maximize osteoinduction and osteoconduction. This is a retrospective analysis of a prospectively collected patient database including 108 patients (204 individual spinal levels). Different surgical procedures performed included 25 anterior cervical discectomy and fusions, 17 posterior cervical fusions, 7 combined anterior and posterior cervical fusions, 10 thoracic fusion surgeries, 18 transforaminal lumbar interbody fusions with 12 axial lumbar interbody fusions, 11 transpsoas discectomy and fusions, and 8 combined thoracolumbar fusion procedures. Si-CaP was used as bone extender without any additional graft material, bone marrow aspirate, or bone morphogenetic protein. Clinical outcomes were assessed using the visual analogue scale (VAS), Oswestry Disability Index, and Neck Disability Index. Fusion was determined by the presence of bony bridging on 2 consecutive sections in at least 2 planes on computed tomographic imaging. At a follow-up of 12 (± 4.7) months, 90% of all patients demonstrated radiographical fusion. Fusion rates were highest in the cervical spine (97%) followed by thoracic and lumbar spines (86% and 81%, respectively). There were significant improvements in all clinical outcome measures-Oswestry Disability Index, 11.1 (± 10.2) and Neck Disability Index, 9.0 (± 11.4); VAS-back, 3.1(± 3.0); VAS-leg, 3.5 (± 3.6); VAS-neck, 3.7 (± 2.5); and VAS-arm 4.0 (± 3.2). There was no radiographical loosening of instrumentation due to infection or nonunion in this series, and no subsequent revisions for nonunion were required. Si-CaP is an alternative to autogenous bone graft in spinal arthrodesis procedures. At 12-month follow-up, we detected high levels of bony fusion using Si-CaP in combination with various surgical spinal techniques.