Hydroxyapatite ceramic implants for cranioplasty in children: a retrospective evaluation of clinical outcome and osteointegration.

INTRODUCTION: Cranioplasty in children is a controversial and challenging issue, since there is still no consensus on the ideal material. Main problems in paediatric age are represented by the child's growing skull, the lower bone thickness and the high incidence of cerebrospinal fluid (CSF) disorders or brain swelling. Autologous bone is still considered the "gold standard". When it is not available, a wide range of alloplastic materials have been proposed. Hydroxyapatite, a ceramic-based derivative, bears a chemical composition very similar to the human natural bone, making this material a valuable alternative to other cranioplasty solutions. METHODS: All patients implanted with a custom-made porous hydroxyapatite device at Santobono-Pausilipon Hospital in Naples were retrospectively reviewed. A follow-up CT scan of the skull was performed from 1 up to 48 months postoperatively to document the bone ingrowth as well as the osteointegration process. The bone density was measured as according to the Hounsfield scale at the bone-implant interface. RESULTS: Between 2014 and 2018, 11 patients (7 males, 4 females) underwent cranioplasty with hydroxyapatite ceramic implants (HAP). Patients' age ranged between 3 and 16 years old. Initial aetiology was trauma in most cases. Two subjects were implanted with HAP as primary cranioplasty, 9 as revision surgery following previous cranioplasty failure. Sites of the cranial defect were unilateral fronto-temporo-parietal (N = 8), unilateral frontal (N = 1) and bifrontal (N = 2). Two patients with large bilateral defects received two prostheses. In one of these, the two prostheses were explanted and replaced with two back-up implants (accounting for a total of 15 implants in 11 patients). Osteointegration was measurable for 12 out of 15 implanted devices. The mean percentage was about 51%. There were six asymptomatic prosthesis fractures (40%), all occurring within 6 months from implant. In one case, the bifrontal prostheses were explanted and replaced. This was the only patient who underwent revision surgery. CONCLUSION: Hydroxyapatite ceramic implants represent a valid alternative to other cranioplasty solutions. Where coaptation occurs correctly, with good osteointegration, implant mechanical resistance increases over time.

Custom-made hydroxyapatite for cranial repair in a specific pediatric age group (7-13 years old): a multicenter post-marketing surveillance study.

BACKGROUND: CustomBone Service (CBS) is a patient-specific, biocompatible, and osteoconductive device made of porous hydroxyapatite, indicated for cranial reconstruction in adults and children. Adult literature data report a failure rate of about 8%. The aim of this Post-Marketing Surveillance study is to verify the hypothesis that CBS in children aged 7-13 years old shows a failure rate not superior to adults. MATERIALS AND METHODS: Inclusion criteria were age at implantation ranging 7-13 years old, with at least 1 year elapsed from the date of surgery. The degree of satisfaction of surgeons and patients was assessed. RESULTS: Data about 76 implants in 67 patients (M:F = 41:26) were obtained from 28 centers across 7 European countries. The mean age at surgery was 10.03 ± 1.72 years, with age stratification almost equally distributed. Fifty-nine subjects received one CBS, 7 subjects two and one subject received three CBS. Main etiologies were trauma (60.5%), malformation (11.8%), bone tumor (10.5%), and cerebral tumor (7.9%). Main indications to CBS were decompression (47.4%), autologous bone resorption (18.4%), tumor resection (11.8%), malformation (9.2%), comminuted fracture (5.3%), and other materials rejection (5.3%). Main implantation sites were fronto-parieto-temporal (26.3%), parietal (23.7%), frontal (11.8%), fronto-temporal (10.5%), and parieto-temporal (7.9%). CBS was chosen as first line of treatment in 63.1% of the cases. Mean follow-up was about 36 months. Eleven adverse events (14.5%) were reported in nine devices. Five CBS required explantation (three cases of infection, one fracture, and one mobilization). Failure rate was 6.58%, which is statistically not superior to the explantation rate recorded in adults (two-sided 95%, CI 2.2-14.7%). Satisfaction of surgeons and patients was of about 95%. CONCLUSION: CBS is a safe and effective solution for cranial repair in pediatric patients. In particular, over the age of 7, CBS shows a rate of failure as low as in adults.

Leukocyte presence does not increase microbicidal activity of Platelet-rich Plasma in vitro.

BACKGROUND: Human platelets are a rich reservoir of molecules that promote regenerative processes and microbicidal activity. This activity might be increased by concentration in platelet-rich plasma (PRP) products and modulated by the presence of leukocytes. Despite extensive use in clinical procedures, only few studies have investigated PRP's real microbicidal potential. Therefore, this study aimed at comparing the in vitro microbicidal activity of platelets and leukocyte-enriched PRP (L-PRP) to pure platelet-rich plasma (P-PRP) and the contribution of leukocytes to microbicidal properties. Antimicrobial effects of P- and L-PRP were tested against Escherichia Coli, Staphylococcus Aureus, Klebsiella Pneumoniae, Pseudomonas Aeruginosa and Enterococcus Faecalis. Furthermore, L-PRP was frozen (L-PRP cryo) to assess whether the preparation maintained in vitro characteristics. Microbicidal proteins released by the three preparations were also evaluated. RESULTS: L-PRP, L-PRP cryo and P-PRP generally induced comparable bacterial growth inhibition for up to 4 h' incubation, range 1-4 log. MIP-1α, RANTES, GRO-α, IL-8, NAP-2, SDF-1α and IL-6 showed strong microbicidal potential. CONCLUSIONS: We found in vitro antibacterial activity of L-PRP and P-PRP and the possibility to cryopreserve L-PRP, without important changes to its effectiveness; similar microbicidal activity between preparations containing or not leukocytes; and the contribution of three new molecules (NAP-2, SDF-1α and IL-6).

Platelet-rich plasma affects bacterial growth in vitro.

BACKGROUND AIMS: Platelet-rich plasma (PRP), a blood derivative rich in platelets, is a relatively new technique used in tissue regeneration and engineering. The increased quantity of platelets makes this formulation of considerable value for their role in tissue healing and microbicidal activity. This activity was investigated against five of the most important strains involved in nosocomial infections (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Streptococcus faecalis) to understand the prophylactic role of pure (P)-PRP. Microbicidal proteins released from activated P-PRP platelets were also determined. METHODS: The microbicidal activity of P-PRP and platelet-poor plasma (PPP) was evaluated on different concentrations of the five bacterial strains incubated for 1, 2, 4 and 18 h and plated on agar for 18-24 h. P-PRP and PPP-released microbicidal proteins were evaluated by means of multiplex bead-based immunoassays. RESULTS: P-PRP and PPP inhibited bacterial growth for up to 2 h of incubation. The effect of P-PRP was significantly higher than that of PPP, mainly at the low seeding concentrations and/or shorter incubation times, depending on the bacterial strain. Chemokine (C-C motif) ligand-3, chemokine (C-C motif) ligand-5 and chemokine (C-X-C motif) ligand-1 were the molecules mostly related to Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis inhibition. Escherichia coli and Klebsiella pneumoniae were less influenced. CONCLUSIONS: The present results show that P-PRP might supply an early protection against bacterial contaminations during surgical interventions because the inhibitory activity is already evident from the first hour of treatment, which suggests that physiological molecules supplied in loco might be important in the time frame needed for the activation of the innate immune response.

Segmental chromosome aberrations converge on overexpression of mitotic spindle regulatory genes in high-risk neuroblastoma.

Integration of genome-wide profiles of DNA copy number alterations (CNAs) and gene expression variations (GEVs) could provide combined power to the identification of driver genes and gene networks in tumors. Here we merge matched genome and transcriptome microarray analyses from neuroblastoma samples to derive correlation patterns of CNAs and GEVs, irrespective of their genomic location. Neuroblastoma correlation patterns are strongly asymmetrical, being on average 10 CNAs linked to 1 GEV, and show the widespread prevalence of long range covariance. Functional enrichment and network analysis of the genes covarying with CNAs consistently point to a major cell function, the regulation of mitotic spindle assembly. Moreover, elevated expression of 14 key genes promoting this function is strongly associated to high-risk neuroblastomas with 1p loss and MYCN amplification in a set of 410 tumor samples (P < 0.00001). Independent CNA/GEV profiling on neuroblastoma cell lines shows that increased levels of expression of these genes are linked to 1p loss. By this approach, we reveal a convergence of clustered neuroblastoma CNAs toward increased expression of a group of prognostic and functionally cooperating genes. We therefore propose gain of function of the spindle assembly machinery as a lesion potentially offering new targets for therapy of high-risk neuroblastoma.

Ceramic bone graft substitute (Mg-HA) in spinal fusion: A prospective pilot study.

Background: Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion due to its known osteoinductive and osteoconductive properties. However, complications related to harvesting procedure and donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. Among all, ceramic-based biomaterials have been widely studied and employed in the last years as bone graft substitutes. Methods: We report here the results of a prospective pilot study aimed to evaluating the grade of ossification obtained by the use of an Mg-doped hydroxyapatite (HA) product to achieve postero-lateral fusion in degenerative spine diseases. Results: Results show a successful degree of fusion of about 62% at the 12-month follow-up and an improvement of quality of life and health status following surgery, as evaluated by clinical scores (ODI, VAS, and EQ-5L). No adverse events related to the material were reported. Conclusion: The present pilot study shows the effectiveness and the safety profile of an Mg-doped HA bone graft substitute used to achieve postero-lateral fusion in the treatment of degenerative spine diseases, laying down the basis for further larger clinical investigations.

A new bioinspired collagen-hydroxyapatite bone graft substitute in adult scoliosis surgery: results at 3-year follow-up.

BACKGROUND: Spinal fusion is a common procedure used for surgical treatment of spinal deformity. In recent years, many bone graft substitutes (BGS) have been developed to provide good arthrodesis when the available autologous bone harvested from the patient is not enough. The aim of this study was to analyze the use of a new-generation composite material (RegenOss) made of Mg-hydroxyapatite nanoparticles nucleated on type I collagen to obtain long posterolateral fusion in adult scoliosis surgery. METHODS: A total of 41 patients who underwent spinal fusion for the treatment of adult scoliosis were retrospectively analyzed. According to Lenke classification, visual analog scale (VAS) score and Oswestry Disability Index (ODI) score, radiographic rates of bone union were evaluated before surgery and at 6, 12 and 36 months of follow-up. Fusion was considered to be successful when criteria for Lenke grade A or B were satisfied. Patient-related risk factors were considered for the evaluation of the final outcome. RESULTS: At 36-month follow-up, radiographic evidence of spinal fusion was present in the majority of patients (95.1%). A time-dependent statistically significant improvement was evidenced after surgery for all clinical outcomes evaluated. Based on the demographic data collected, there were no statistically significant factors determining fusion. The correction of deformity was maintained at different time points. No intraoperative or postoperative complications were recorded. CONCLUSIONS: The present study demonstrated that RegenOss can safely be used to achieve good arthrodesis when associated with autologous bone graft to obtain long spinal fusion in the treatment of adult scoliosis.

Leukocyte-Rich Platelet-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee.

INTRODUCTION: The presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet-rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation. METHODS: Thirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF-AB/BB). RESULTS: In general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors. CONCLUSIONS: In contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators.