In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use.
The purpose of the current investigation was to evaluate the clinical success of horizontal ridge augmentation in severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from the tibial hemiplateau of cadaver donors, and to analyze the marginal bone level gain prior to dental implant placement at nine months subsequent to bone grafting and before prosthetic rehabilitation. A 52-year-old woman received custom made bone grafts. The patient underwent CT scans two weeks prior and nine months after surgery for graft volume and density analysis. The clinical and radiographic bone observations showed a very low rate of resorption after bone graft and implant placement. The custom-made allograft material was a highly effective modality for restoring the alveolar horizontal ridge, resulting in a reduction of the need to obtain autogenous bone from a secondary site with predictable procedure. Further studies are needed to investigate its behavior at longer time periods.
Background
A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period.
Methods
Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. Evaluations: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. Statistical analysis: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons.
Results
KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group.
Conclusions
The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease.
Trial registration
NCT02417610.
Registration, 15/04/2015.
ClinicalTrials.gov database link:
Human bone is a specialized tissue with unique material properties, providing mechanical support and resistance to the skeleton and simultaneously assuring capability of adaptation and remodelling. Knowing the properties of such a structure down to the micro-scale is of utmost importance, not only for the design of effective biomimetic materials but also to be able to detect pathological alterations in material properties, such as micro-fractures or abnormal tissue remodelling. The Brillouin and Raman micro-spectroscopic (BRmS) approach has the potential to become a first-choice technique, as it is capable of simultaneously investigating samples’ mechanical and structural properties in a non-destructive and label-free way. Here, we perform a mapping of cortical and trabecular bone sections of a femoral epiphysis, demonstrating the capability of the technique for discovering the morpho-mechanics of cells, the extracellular matrix, and marrow constituents. Moreover, the interpretation of Brillouin and Raman spectra merged with an approach of data mining is used to compare the mechanical alterations in specimens excised from distinct anatomical areas and subjected to different sample processing. The results disclose in both cases specific alterations in the morphology and/or in the tissue chemical make-up, which strongly affects bone mechanical properties, providing a method potentially extendable to other important biomedical issues.
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