Calcium-Zinc Phosphate Chemical Conversion Coating Facilitates the Osteointegration of Biodegradable Zinc Alloy Implants by Orchestrating Macrophage Phenotype.

Zinc (Zn) alloys provide a new generation for orthopedic applications due to their essential physiological effects and promising degradation properties. However, excessive release of Zn ions (Zn2+ ) during degradation and the severe inflammatory microenvironment are not conducive to osseointegration, which is determined by the characteristics of the implant surface. Therefore, it is essential to modulate the release rate of Zn alloys by surface modification technology and endow them with anti-inflammatory and osteogenic effects. In this study, two kinds of phosphate chemical conversion (PCC) coatings with different compositions and morphological structures are prepared, namely Zn-P (with disk-like crystals) and Ca-Zn-P (with lamellar crystals). Although all the PCC-coated Zn implants have low cytotoxicity, Ca-Zn-P show better osteoimmunomodulation effects in several aspects: the induction of the M2-phenotype macrophage polarization and thus promotion of osteogenesis in vitro; the regulation of the bone immune microenvironment which is conducive to tissue regeneration and osseointegration in vivo; and the release of ions (through PI3K/AKT and Wnt signaling pathways) and the morphological structures (through RhoGTPase signaling pathways) act as possible mechanisms of M2 polarization. The Ca-Zn-P coating can be considered to provide new insights into bone immunomodulation and osseointegration.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.