Security and reliability of CUSTOMBONE cranioplasties: A prospective multicentric study.

BACKGROUND: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis. OBJECTIVE: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years. RESULTS: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection. CONCLUSION: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary.

Biomaterials as bone graft substitutes for spine surgery: from preclinical results to clinical study.

Vertebral fusion is performed in order to stabilize the spine in the presence of degenerative, traumatic or oncological pathologies that alter its stability. The autologous bone, harvested from the patient's iliac crest or from the lamina during surgery, is still considered the "gold standard" for spine fusion due to its osteogenic, osteoinductive and osteoconductive properties. However, several biological and synthetic bone substitutes have been introduced as alternatives for regenerating bone tissue. We have studied in particular the use of ceramic biomaterials prepared from hydroxypatite (HA), starting from in vitro analysis, through an in vivo study on ovine animal model and a post-market surveillance analysis, to finally design and perform a clinical study, which is ongoing in our Department. In the first step, HA-derived biomaterials were tested in vitro in the presence of bone marrow-derived human mesenchymal stem cells (hMSCs) and evaluated for their ability to activate precursor cells. In the second step, the biomimetic bone graft substitute SintLife® putty (MgHA) was evaluated in vivo. A posterolateral fusion procedure was applied on 18 sheep, where a fusion level was treated with MgHA, while the other level was treated with autologous bone. Microtomography and histological/histomorphometric analysis were performed six months of after surgery. In the third step, we reported the results of a post-market surveillance study conducted on 4 independent cohorts of patients (total 115 patients), in which HA-derived biomaterials were used as bone graft substitutes or extenders. Finally, a clinical study has been designed and approved by the Ethics Committee of our Institute and is currently ongoing. This study aims to evaluate the efficacy of the ceramic biomaterial SintLife® putty for bone replacement in patients treated by posterolateral fusion for degenerative spine disorders. HA biomaterials were effective in promoting the in vitro growth of hMSCs and their osteogenic differentiation. In the animal model, SintLife® putty has been effective in generating neo-formed bone tissue with morphological and structural features similar to those of the pre-existing bone. The post-market surveillance analysis has not reported any intra-operative nor early or late post-operative adverse events. Seven patients are currently recruited for the clinical trial designed to evaluate Sintlife efficacy for spine fusion (FU range: 1-7 months). No adverse events have been recorded. The first CT analysis performed at 6 months FU showed a good spine fusion. The study is ongoing. Our results, obtained from in vitro, preclinical and clinical studies, suggest that biomaterials derived from hydroxyapatite could be a valid alternative to autologous bone graft for vertebral fusion. This would potentially avoid or reduce the need of autologous bone harvesting and therefore, the risk of drawback-related side effects.

Custom made cranioplasty prostheses in porous hydroxy-apatite using 3D design techniques: 7 years experience in 25 patients.

BACKGROUND: None of the materials currently used to reconstruct skull defects is fully satisfactory. Their biological and physical properties are very different to those of natural bone. Solid state, high porosity hydroxy-apatite (HA) seems to be a good support for bone regeneration within the prostheses, enabling integration of the heterologous material with low post-implant infective risk. MATERIALS AND METHODS: A model of the cranium of each patient was made in epoxy resin by stereolithography. The prosthesis was built on this model using a ceramic sintering process. In each case, an exact copy of the missing bone flap was obtained (curvature, dimensions, margins, irregularities and thickness). The porosity obtained is the same as that of the spongy bone of the skull with interconnected macropores (>150 microm) to promote osteoblast migration into the prosthetic core. In The Neurosurgery Division of Cesena, 26 cranioplasty prostheses have been implanted with this technique in 7 years (from 1998 to 2004). No particular criteria were pre-established, but the main indications for use of ceramic prostheses were complex and/or extended (surface >25 cm(2)) post-surgery craniolacuna and/or previous unsuccessful procedures due to rejection, infection or bone flap reabsorption. RESULTS: Twenty-five patients were included in this study. A clinical check-up and 3D CT (mean follow-up 30 months, range 12-79) always showed an excellent aesthetic result. No cases of infection, rejection or spontaneous prosthesis fragmentation were found. The surgical procedure was simpler and shorter than for other described procedures. CONCLUSIONS: Bioceramic porous hydroxy-apatite prosthesis have been demonstrated as a valid alternative to traditional cranioplasty techniques both aesthetically and in terms of absence of infections/rejections. Principal limitations for the use of HA prostheses are the need for stereolithography process, the poor malleability of the material and the high cost.