Gradients of three-dimensional (3D) hierarchical tissues are common in nature and present specific architectures, as this is the case of the anisotropic subchondral bone interfaced with articular cartilage. While diverse fabrication techniques based on 3D printing, microfabrication, and microfluidics have been used to recreate tailored biomimetic tissues and their respective microenvironment, an alternative solution is still needed for improved biomimetic gradient tissues under dynamic conditions with control over pre-vasculature formation. Here, we engineered a gradient osteochondral human-based tissue with precise control over both cell/tissue phenotype and pre-vasculature formation, which opens-up possibilities for the study of complex tissues interfaces, with broader applications in drug testing and regenerative medicine.

The fabrication of 3D gradients of microparticles was performed combining methacrylated gelatin (GelMA) and gellan gum (GG) (3:1, w:w ratio) with hydroxyapatite microparticles (HAp, 30% w/w). The mixing of the interface was controlled by the temperature of two polymeric layers, being the second added at 10 ºC higher than the first one. This subsequent addition of polymeric solutions at different temperatures promoted convection, which drove the microparticles through the interface from the first to the second layered gel forming the HAp gradient. After ionic and photo-crosslinking, the freezing step was programmed using an external cover of styrofoam forcing the ice crystals to grow linearly, generating an anisotropic architecture in a gradient scaffold. A dual-chamber microreactor device was designed (figure 1A) to culture fat pad adipose-derived stem cells and microvascular endothelial cells under two biochemical microenvironments.

Using control over temperature and crosslinking, hydrogel-like structures were built in 3D anisotropic HAp gradients. Then, an in vitro osteochondral tissue model was obtained using a dual-chamber platform. Results showed a significant difference of SOX9 (p < 0.05), Osteocalcin and RUNX2 (p < 0.05) from the top to the bottom regions of the 3D gradient structures under dynamic conditions. Finally, a pre-vasculature was controlled over 7 days, stimulating the endothelization of the subchondral bone-like region 35% more (p < 0.05) when compared to the cartilage-like region.

In this work, microparticle and biochemical gradients were fabricated into anisotropic architectures. The obtained outcomes enable the precise control of 3D gradients in programmable architectures, such as anisotropic structures, with broad applications in interfaced tissue engineering, regenerative medicine and drug testing.

Introduction: Most of the bone metastases have origin in breast, lung, prostate, thyroid and kidney neoplasms. The commonest locations are the axial skeleton and the proximal region of the long bones, being the femur the most affected one. The main objectives of the surgical treatment are a quick functional recuperation and immediate pain relief.

Objectives: The aim of this work was to define a strategy for the surgical treatment of the bone methastasis located in the femur.

Material: The study includes 94 patients with femoral methastasis (100 metastasis) surgicaly treated in the last 10 years in our department.

Methods: Retrospective descriptive study based on medical records evaluation.

Results: The proximal third of the femur was involved in 80 % of the cases. Pathological fracture was identified in 72 cases and impending fracture in 28. Half of the primitive neoplasms was originated in the breast. It was identified as solitary metastatic lesion only in 33 % of the situations. The mean patient survival time was 9,2 months. They were treated with a cemented calcar-replacing prosthesis in 40 patients, 10 patients submited to conventional arthroplasty and 36 with intramedullary fixation (usually a cephalomedullary nail). The remainder 14 were treated with other surgical techniques.

Discussion: The surgery is indicated in case of painful lytic injury or unresponsive to radiotherapy, pathological or impending fracture. The surgical technique depends on the location and size of the lesion and if it is a solitary or multiple bone lesion, choosing between arthroplasties, of preference with long femoral stem, and intramedullary fixation. As we have performed a retrospective study, a functional rigorous evaluation was not possible.

Conclusion: The treatment of metastatic femoral disease is not performed with the intention of cure but to improve significantly the patient’s life quality. The proximal third of the femur is the most reached place. Breast cancer was responsible for around 50 % of the cases. In 50% of the patients the surgical option was an arthroplasty and techniques of femoral nailing were performed in 36%. The cemented replacement prosthesis is used in proximal large injuries with periarticular involvement: The intramedullary fixation is reserved for situations in which the femoral head and neck are not involved. The length of patient survival must exceed the predictable surgical recovery period.

Introduction: Soft tissue sarcomas (STS) are rare tumors. A multidisciplinary approach including surgery, chemotherapy and radiation therapy is recommended.

Materials and Methods: In the last 12 years, 249 patients with STS were teated in our Institution. All of them were treted with a multidisciplinary approach using all or some of the previous refered treatments.

Results: The overall local recurrence rate in the group of patients submited to surgery was 25% and this factor was related mostly with contaminated margins. Surgical resections were associted with soft tissue reconstructions when needed.

Radiation therapy was used in both regimens pre and post operativly, chemotherapy was also used in 85% of the patients, and was not dependent of tumor histotype.

23 patients were submited to surgery of lung metastasis.

Survival rates were determined and compared with stage (AJCC), tumor histotype and surgical margins.

Conclusions: Multidisciplinary approach is the recommended treatment for STS.