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Purpose This study aimed to evaluate the early stability, limb function, and mechanical complications of 3D-printed porous prosthetic reconstruction for “ultra-critical sized bone defects” following intercalary tibial tumor resections. Methods This study defined an “ultra-critical sized bone defect” in the tibia when the length of segmental defect in the tibia was >15.0 cm or >60% of the full tibia and the length of the residual fragment in proximal or distal tibia was between 0.5 cm and 4.0 cm. Thus, five patients with “ultra-critical sized bone defects” following an intercalary tibial malignant tumor resection treated with 3D-printed porous prosthesis between June 2014 and June 2018 were retrospectively reviewed. Patient information, implants design and fabrication, surgical procedures, and early clinical outcome data were collected and evaluated. Results Among the five patients, three were male and two were female, with an average age of 30.2 years. Pathological diagnoses were two osteosarcomas, one Ewing sarcoma, one pseudo-myogenic hemangioendothelioma, and one undifferentiated pleomorphic sarcoma . The average length of the bone defects following tumor resection was 22.8cm, and the average length of ultra-short residual bone was 2.65cm (range=0.6cm–3.8cm). The mean follow-up time was 27.6 months (range=14.0–62.0 months). Early biological fixation was achieved in all five patients. The average time of clinical osseointegration at the bone–porous interface was 3.2 months. All patients were reported to be pain free and have no limitations in their walking distance. No prosthetic mechanical complications were observed. Conclusion Reconstruction of the “ultra-critical sized bone defect” after an intercalary tibial tumor resection using 3D-printed porous prosthesis achieved satisfactory overall early biological fixation and limb function. Excellent primary stability and the following rigid biological fixation were key factors for success. The outcomes of this study were supposed to support further clinical application and evaluation of 3D-printed porous prosthetic reconstruction for “ultra-critical sized bone defects” in the tibia.

Chuanxi Zheng,* Yong Zhou,* Yitian Wang, Yi Luo, Chongqi Tu, Li Min Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li MinDepartment of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, People’s Republic of ChinaTel +86 13760311476Fax +86 028 85582944Email minli1204@scu.edu.cnPurpose: Desmoid fibromatosis (DF) is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Although multiple therapeutic modalities seem effective for DF, the standard systemic treatment for symptomatic and progressive DF remains controversial. As targeted therapy, tyrosine kinase inhibitors have been recently reported to contribute to the treatment of DF. Thus, the purpose of this study was to assess the efficacy and safety of anlotinib, a novel multi-kinase angiogenesis inhibitor, in patients with DF.Patients and Methods: We retrospectively collected the clinical medical records of patients with extremity DF who received anlotinib between January 2019 and January 2020 in our center. Anlotinib was started with a dose of 8 mg daily and adjusted according to the drug-related toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival (PFS) was identified as the primary endpoint and analyzed using the Kaplan–Meier method.Results: In total, 21 (6 male, 15 female) consecutive patients with DF were enrolled. The median medication time was nine months (Q1, Q3: 7.5, 10.5). None of the patients achieved a complete response, but eight (38.1%) patients achieved a partial response and ten patients (47.6%) achieved disease stability. Three (14%) patients developed progressive disease and the 3-, 6-, and 12-month PFS rates were 95.2%, 90.5%, and 84.0%, respectively. The disease control rate was 86.0% (18/21) and the objective response rate was 38.1% (8/21). Moreover, 15/21 (71.4%) patients achieved a reduction in tumor size, accompanied with a decrease in T2-weighted signal intensity on magnetic resonance imaging and clinical benefit.Conclusion: Anlotinib was effective against DF with an acceptable safety profile, and significantly slowed the disease progression. Further, multicenter studies with a longer follow-up time are needed to characterize fully the clinical application of anlotinib in DF.Keywords: desmoid fibromatosis, anlotinib, tyrosine kinase inhibitor, targeted therapy

Wang Y, Lu M, Zhou Y, et al. Cancer Manag Res.2020;12:5255–5264. The authors have advised that there is an error in Table 1on page 5257. The value “26.00” in the Median row forAge(years) should read “31.5”. The authors have also advised that there is an error inTable 2 on page 5258. The column heading “OverallSurvival” should read “Overall Follow-up Time”. The authors apologize for these errors and advise it doesnot affect the conclusions of the paper. Read the original article

Xi Fu,1 Pin Liu,1 Dingyun Zhao,2 Bo Yuan,1 Zhanwen Xiao,1 Yong Zhou,2 Xiao Yang,1 Xiangdong Zhu,1 Chongqi Tu,2 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of China; 2Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Xiangdong ZhuNational Engineering Research Center for Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, People’s Republic of ChinaTel +86 28 8547 0770Email zhu_xd1973@scu.edu.cnChongqi TuDepartment of Orthopaedics, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, People’s Republic of ChinaTel +86 28 8542 2570Email tcqbonetumor@163.comBackground: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects.Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro.Materials and Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments.Results: By controlling Si content in ∼ 0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect.Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.Keywords: electrochemical deposition, hydroxyapatite, silicon, coating, morphology, MC3T3-E1 cells, HUVECs

Jing Wang,1 Menglu Wang,1 Fuying Chen,1 Yihang Wei,1 Xuening Chen,1 Yong Zhou,2 Xiao Yang,1 Xiangdong Zhu,1 Chongqi Tu,2 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of China; 2Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Xuening Chen; Xiangdong ZhuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of ChinaEmail xchen6@scu.edu.cn; zhu_xd1973@scu.edu.cnBackground: The hierarchical porous structure and surface topography of calcium phosphate (CaP) bioceramics have a crucial impact on their osteoinductivity.Purpose: To fabricate a biomimetic bone graft with an interconnected porous structure analogous to that of trabecular bone and a bioactive nanostructured surface with excellent osteoinductive potential.Materials and methods: A biphasic CaP (BCP) substrate with highly porous structure was fabricated by an improved sponge replication method. Surface modification was performed by uniformly depositing a hydroxyapatite (HA) nanoparticle layer to create nHA-coated BCP scaffolds. The effects of these scaffolds on osteogenic differentiation of murine bone marrow-derived stem cells (BMSCs) were investigated in vitro, and their osteoinductivity was further assessed in vivo.Results: The BCP and nHA-coated BCP scaffolds had similar trabecular bone-like architectures but different surface structures, with mean grain sizes of ∼55 nm and ∼1 μm, respectively. Compared with the BCP substrate, the nHA-coated BCP scaffolds favored cell adhesion and promoted osteogenic differentiation of BMSCs, as evidenced by upregulated expression of osteogenic genes, enhanced alkaline phosphatase activity, and increased osteocalcin production. This could be attributed to activation of the BMP/Smad signaling pathway, as significantly higher expression levels of BMPRI, Smad1, Smad4, and Smad5 were observed in the nHA-coated BCP group. The nHA-coated BCP scaffold not only maintained scaffold integrity but also induced ectopic bone formation when implanted into rabbit dorsal muscle in vivo for 90 days, whereas the BCP substrate underwent marked biodegradation that led to severe inflammation with no sign of osteogenesis.Conclusion: The present study demonstrates the potential of this biomimetic bone graft with a trabecular framework and nanotopography for use in orthopedic applications.Keywords: nano-hydroxyapatite, calcium phosphate ceramics, porous scaffolds, MSCs, osteoblastic differentiation, osteoinduction

Yitian Wang,* Li Min,* Yong Zhou, Fan Tang, Yi Luo, Wenli Zhang, Hong Duan, Chongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People‘s Republic of China*These authors contributed equally to this workBackground: Evidence suggests that advanced or metastatic alveolar soft part sarcoma (ASPS) with high metastatic potential is chemo-resistant. However, the benefits of tyrosine kinase inhibitors have been demonstrated for the treatment of ASPS.Purpose: This study aimed to investigate the efficacy and safety of apatinib, aspecific VEGFR-2 inhibitor, in ASPS patients. This retrospective analysis involved six patients with metastatic ASPS not amenable to curative treatment.Patients and methods: Apatinib was administered at a dose of 500mg per day. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines. Survival analysis was performed using the Kaplan–Meier test, and a safety profile was recorded.Results: The mean age of patients was 26.5 (range, 17–32) years. The median progression-free survival (PFS) was 18.53 months (95% CI, 12.23-NE). However, median overall survival (OS) has not been reached. Twenty-four month PFS and OS rates were 50.0% and 100.0%, respectively. One patient achieved a complete response, and the remaining patients achieved partial responses, with an objective response rate of 100%. Median follow-up was 20.6 (range, 12.43–34.13) months. The most common adverse events included gastrointestinal discomfort (4/6[66.7%]), hair hypopigmentation (4/6[66.7%]) and hand-foot skin reaction (3/6[50.0%]).Conclusion: Apatinib shows beneficial activity in metastatic ASPS patients, and further studies are warranted with more cases and longer follow-up periods to fully characterize clinical efficacy and safety of apatinib in ASPS.Keywords: alveolar soft part sarcoma, apatinib, efficacy, safety, vascular endothelial growth factor

Hongfeng Wu,1 Zhongtao Li,2 Jiaoqing Tang,2 Xiao Yang,1 Yong Zhou,3 Bo Guo,4 Lin Wang,2 Xiangdong Zhu,1 Chongqi Tu,3 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; 2Department of Dermatology, West China Hospital of Sichuan University, Chengdu 610041, China; 3Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, China; 4Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu 610041, China Background: Treatment for melanoma is a challenging clinical problem, and some new strategies are worth exploring.Purpose: The objective of this study was to investigate the in vitro and in vivo anti-melanoma effects of hydroxyapatite nanoparticles (HANPs) and discuss the involved material factors.Materials and methods: Five types of HANPs, ie, HA-A, HA-B, HA-C, HA-D, and HA-E, were prepared by wet chemical method combining with polymer template and appropriate post-treatments. The in vitro effects of the as-prepared five HANPs on inhibiting the viability of A375 melanoma cells and inducing the apoptosis of the cells were evaluated by Cell Counting Kit-8 analysis, cell nucleus morphology observation, flow cytometer, and PCR analysis. The in vivo anti-melanoma effects of HANPs were studied in the tumor model of nude mice.Results: The five HANPs had different physicochemical properties, including morphology, size, specific surface area (SSA), crystallinity, and so on. By the in vitro cell study, it was found that the material factors played important roles in the anti-melanoma effect of HANPs. Among the as-prepared five HANPs, HA-A with granular shape, smaller size, higher SSA, and lower crystallinity exhibited best effect on inhibiting the viability of A375 cells. At the concentration of 200 µg/mL, HA-A resulted in the lowest cell viability (34.90%) at day 3. All the HANPs could induce the apoptosis of A375 cells, and the relatively higher apoptosis rates of the cells were found in HA-A (20.10%) and HA-B (19.41%) at day 3. However, all the HANPs showed no inhibitory effect on the viability of the normal human epidermal fibroblasts. The preliminary in vivo evaluation showed that both HA-A and HA-C could delay the formation and growth speed of melanoma tissue significantly. Likely, HA-A exhibited better effect on inhibiting the growth of melanoma tissue than HA-C. The inhibition rate of HA-A for tumor tissue growth reached 49.1% at day 23.Conclusion: The current study confirmed the anti-melanoma effect of HANPs and provided a new idea for the clinical treatment of melanoma. Keywords: hydroxyapatite, nanoparticles, melanoma cells, fibroblasts, viability, apoptosis, tumor, suppression