Modulation of the hepatic RANK-RANKL-OPG axis by combined C5 and CD14 inhibition in a long-term polytrauma model.

Background: Polytrauma and hemorrhagic shock can lead to direct and indirect liver damage involving intricate pathophysiologic mechanisms. While hepatic function has been frequently highlighted, there is minimal research on how the receptor activator of the NF-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system is regulated in the liver following trauma. Furthermore, cross-talking complement and toll-like-receptor (TLR) systems can contribute to the posttraumatic response.

Biomechanical analysis of a magnesium plantar plate prototype system for the first tarsometatarsal joint fusion: a cadaveric study.

Background: Titanium plantar plates have proven successful in the fixation of the first tarsometatarsal arthrodesis (TMT). However, a second surgery is typically needed for implant removal, and potential adverse effects, carried by the conventional implantations, are not uncommon. The purpose of this study was to determine whether a novel magnesium-based plantar plate system provides similar fusion stability to a titanium-based plantar plate system under various loading conditions.

osteogenic and angiogenic effects of a family of natural origin PO-free bioactive glasses.

Bioactive glasses (BGs) belong to a group of ceramic biomaterials having numerous applications due to their excellent biocompatibility and bioactivity. Depending on their composition, properties of BGs can be finely tuned. In this study, we investigated both angiogenic and osteogenic properties of a novel family of BGs from the SiO-CaO-NaO system.

Pulmonary miRNA expression after polytrauma depends on the surgical invasiveness and displays an anti-inflammatory pattern by the combined inhibition of C5 and CD14.

Background: Respiratory failure can be a severe complication after polytrauma. Extensive systemic inflammation due to surgical interventions, as well as exacerbated post-traumatic immune responses influence the occurrence and progression of respiratory failure. This study investigated the effect of different surgical treatment modalities as well as combined inhibition of the complement component C5 and the toll-like receptor molecule CD14 (C5/CD14 inhibition) on the pulmonary microRNA (miRNA) signature after polytrauma, using a translational porcine polytrauma model.

Lactate dehydrogenase can be used for differential diagnosis to identify patients with severe polytrauma with or without chest injury-A retrospective study.

Background: Chest injury is an important factor regarding the prognosis of patients with polytrauma (PT), and the rapid diagnosis of chest injury is of utmost importance. Therefore, the current study focused on patients' physiology and laboratory findings to quickly identify PT patients with chest injury.

Method: Data on 64 PT patients treated at a trauma center level I between June 2020 and August 2021 were retrospectively collected.

Discovering the nucleus in a world of biomaterials.

The nucleus serves as the central hub for cellular activity, driving cell identity and behavior. Despite its crucial role, understanding how biomaterials influence the nucleus remains an underexplored area of research. In our opinion, this is an overlooked opportunity, particularly in regenerative medicine - a field where cellular control is not just beneficial, but essential.

Porcine Mandibular Bone Marrow-Derived Mesenchymal Stem Cell (BMSC)-Derived Extracellular Vesicles Can Promote the Osteogenic Differentiation Capacity of Porcine Tibial-Derived BMSCs.

Objective: Existing research suggests that bone marrow-derived mesenchymal stem cells (BMSCs) may promote endogenous bone repair. This may be through the secretion of factors that stimulate repair processes or directly through differentiation into osteoblast-progenitor cells. However, the osteogenic potential of BMSCs varies among different tissue sources (e.

Extracellular vesicles are key players in mesenchymal stem cells' dual potential to regenerate and modulate the immune system.

MSCs are used for treatment of inflammatory conditions or for regenerative purposes. MSCs are complete cells and allogenic transplantation is in principle possible, but mostly autologous use is preferred. In recent years, it was discovered that cells secrete extracellular vesicles.

Extracellular vesicles derived from endothelial cells modulate macrophage phenotype in vitro.

Extracellular vesicles (EVs) mediate cell-to-cell communication by horizontally transferring biological materials from host cells to target cells. During exposure to pathogens, pathogen-associated molecular patterns (e.g.

Cellular uptake of modified mRNA occurs via caveolae-mediated endocytosis, yielding high protein expression in slow-dividing cells.

Nucleic acids have clear clinical potential for gene therapy. Plasmid DNA (pDNA) was the first nucleic acid to be pursued as a therapeutic molecule. Recently, mRNA came into play as it offers improved safety and affordability.

MiRNAs as Potential Regulators of Enthesis Healing: Findings in a Rodent Injury Model.

MicroRNAs (miRNAs) are short non-coding RNA sequences with the ability to inhibit the expression of a target mRNA at the post-transcriptional level, acting as modulators of both the degenerative and regenerative processes. Therefore, these molecules constitute a potential source of novel therapeutic tools. In this study, we investigated the miRNA expression profile that presented in enthesis tissue upon injury.

Osteoblast derived extracellular vesicles induced by dexamethasone: A novel biomimetic tool for enhancing osteogenesis .

Extracellular vesicles (EVs) are newly appreciated communicators involved in intercellular crosstalk, and have emerged as a promising biomimetic tool for bone tissue regeneration, overcoming many of the limitations associated with cell-based therapies. However, the significance of osteoblast-derived extracellular vesicles on osteogenesis has not been fully established. In this present study, we aim to investigate the therapeutic potential of extracellular vesicles secreted from consecutive 14 days of dexamethasone-stimulated osteoblasts (OB-EV) to act as a biomimetic tool for regulating osteogenesis, and to elucidate the underlying mechanisms.

The addition of zinc ions to polymer-ceramic composites accelerated osteogenic differentiation of human mesenchymal stromal cells.

Critical-sized bone defects, caused by congenital disorders or trauma, are defects that will not heal spontaneously and require surgical intervention. Recent advances in biomaterial design for the treatment of such defects focus on improving their osteoinductive properties. Here, we propose a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50 % beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating on the TCP particles.

SULFORAPHANE ADMINISTRATION AFTER HEMORRHAGIC SHOCK/RESUSCITATION IN MICE REDUCES THE SECRETION OF INFLAMMATORY CYTOKINES AND INCREASES THE IMMUNOCOMPETENCE OF SPLENIC MACROPHAGES.

Objective : The purpose of this study was to investigate the immunomodulatory effects of sulforaphane (SFN), a nuclear factor erythroid 2-related factor (Nrf2) pathway activator, on splenic macrophages' immunocompetence after hemorrhagic shock/resuscitation (HS/R). Methods : Male C57/BL6 wild-type mice (n = 6 per group) were subjected to either pressure-controlled HS (MAP, 35-45 mm Hg) or a sham procedure surgery (without HS). After 90 minutes of HS, fluid resuscitation with withdrawn blood and 0.

Specific microRNAs are associated with fracture healing phases, patient age and multi-trauma.

Background: Immediately after a fracture occurs, a fracture hematoma (fxH) is formed. This fxH plays an important role in fracture healing and, under normal circumstances, aids in generating an environment in which a wide variety of cells orchestrate processes involved in fracture healing. MicroRNAs (miRNAs) may influence these processes.

Enthesis: not the same in each localisation - a molecular, histological and biomechanical study.

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location.

Enthesis Healing Is Dependent on Scaffold Interphase Morphology-Results from a Rodent Patellar Model.

The use of multiphasic scaffolds to treat injured tendon-to-bone entheses has shown promising results in vitro. Here, we used two versions of a biphasic silk fibroin scaffold to treat an enthesis defect created in a rat patellar model in vivo. One version presented a mixed transition between the bony and the tendon end of the construct (S-MT) while this transition was abrupt in the second version (S-AT).

Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2.

Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA).

Synthetic mRNA - emerging new class of drug for tissue regeneration.

mRNA has the potential to be the next generation drug for tissue restoration in regenerative medicine. The variety of mRNAs that could be synthesized with the aim of increasing the expression of any required protein offers new opportunities. However, the intrinsic immunogenicity and lack of stability of mRNA has long restricted the potential of mRNA therapeutics.

Phosphorous pentoxide-free bioactive glass exhibits dose-dependent angiogenic and osteogenic capacities which are retained in glass polymeric composite scaffolds.

Bioactive glasses (BGs) are attractive materials for bone tissue engineering because of their bioactivity and osteoinductivity. In this study, we report the synthesis of a novel phosphorous pentoxide-free, silicate-based bioactive glass (52S-BG) composed of 52.1% SiO, 23.

Gene therapy for bone healing: lessons learned and new approaches.

Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use.