MicroRNA (miR) delivery to regulate chronic inflammation hold extraordinary promise, with new therapeutic possibilities emanating from their ability to fine-tune multiple target gene regulation pathways which is an important factor in controlling aberrant inflammatory reactions in complex multifactorial disease. However, several hurdles have prevented advancements in miR-based therapies. These include off-target effects of miRs, limited trafficking, and inefficient delivery. We propose a magnetically guided nanocarrier to transport therapeutically relevant miRs to assist self- resolving inflammation processes at injury sites and reduce the impact of chronic inflammation- related diseases such as tendinopathies. The high prevalence, significant socio-economic burden and increasing recognition of dysregulated immune mediated pathways in tendon disease provide a compelling rationale for exploring inflammation-targeting strategies as novel treatments in this condition. By combining cationic polymers, miR species (e.g., miR 29a, miR155 antagonist), and magnetic nanoparticles in the form of magnetoplexes with highly efficient magnetofection procedures, we developed inexpensive, easy-to-fabricate, and biocompatible systems with competent miR-binding and fast cellular uptake into different types of human cells, namely macrophages and tendon-derived cells. The system was shown to be cell-compatible and to successfully modulate the expression and production of inflammatory markers in tendon cells, with evidence of functional pro-healing changes in immune cell phenotypes. Hence, magnetoplexes represent a simple, safe, and non-viral nanoplatform that enables contactless miR delivery and high- precision control to reprogram cell profiles toward improved pro-regenerative environments.

Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM

RES Hub (Norte-01-0145-FEDER-022190).

Chronic inflammatory events have been associated to almost every chronic disease, including cardiovascular-, neurodegenerative- and autoimmune- diseases, cancer, and host-implant rejection. Given the toll of chronic inflammation in healthcare and socioeconomical costs developing strategies to resolve and control chronic states of inflammation remain a priority for the significant benefit of patients.

Macrophages (Mφ) hold a central role both in the initiation and resolution of inflammatory events, assuming different functional profiles. The outstanding features of Mφ counting with the easy access to tissues, and the extended networking make Mφ excellent candidates for precision therapy. Moreover, sophisticated macrophage-oriented systems could offer innovative immune-regulatory alternatives to effectively regulate chronic environments that traditional pharmacological agents cannot provide.

We propose magnetically assisted systems for balancing Mφ functions at the injury site. This platform combines polymers, inflammatory miRNA antagonists and magnetically responsive nanoparticles to stimulate Mφ functions towards pro-regenerative phenotypes. Strategies with magnetically assisted systems include contactless presentation of immune-modulatory molecules, cell internalization of regulatory agents for functional programming via magnetofection, and multiple payload delivery and release.

Overall, Mφ-oriented systems stimulated pro-regenerative functions of Mφ supporting magnetically assisted theranostic nanoplatforms for precision therapies, envisioning safer and more effective control over the distribution of sensitive nanotherapeutics for the treatments of chronical inflammatory conditions.

Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM

RES Hub (Norte-01-0145-FEDER-022190).

Introduction

The purpose of this study was to compare pre-operative acetabular cup parameters using this novel dynamic imaging sequence to the Lewinnek safe zone

Introduction: Intraarticular fractures of distal radius are associated with high energy mechanisms, are severe and difficult to obtain a surgical reduction. The aim of our paper is to compare the clinical, radiographically and activity results in workers treated with surgical and conservative procedures.

MATERIAL AND METHODS: A prospective study was organized in 43 heavy-labour workers (34 male and 9 female) with unstable fractures of distal radius, treated between 2003 and 2005. The minimal follow-up was of one year. The mean age were 40 years (22–65 years) and dominant limb was involved in 40% of the cases. To treatment groups were established. Group 1, conservative treated with indirect reduction and cast immobilization (n=20) and Group 2 surgically treated with indirect reduction and percutaneous fixation with K-wires and cast immobilization (n=24).

Pain, mobility and radiograhs were evaluated and also strength (isokinetics), functionality (DASH score) and, finally, the return to work at 3, 6 and 12 months.

RESULTS: Fracture healing was obtained at 7 weeks but the time to return to work were 14 weeks after surgery. Pain score, at 12 months, were 2,3 points for conservative treatment and 2,9 points for the surgically group. The flexion – extension mobility loss, in relation to the contralateral wrist, was lesser in the conservative group at 3 and 6 month but similar (11°) at 12 months in both groups. Radiographs corrections were anatomically in 38% of the cases of group 1 and in 80% of group 2. Functional and strength results were similar in both groups. All the patients return to the same work activity.

CONCLUSIONS: Percutaneous fixation of unstable intraarticular distal radius fracture is comparable to the conservative treatment but the percentage of anatomical reductions was higher. It would be of importance in the evolution of the patients.