Exploring the effect of hydroxyapatite nanoparticle shape on red blood cells and blood coagulation.

Aim: In this study, we evaluated the effects of two types of hydroxyapatite (HAP) nanoparticles, sharing the same surface chemistry but differing in shape, on the biological characteristics of plasma, platelets and red blood cells.Materials & methods: Initially, two different shapes (rod-shaped and sphere-shaped) of HAPs were characterized. These HAPs were then co-cultured with plasma and red blood cells to examine their impact on coagulation and hemolysis. The impact of HAPs on white blood cells count in mice were evaluated following gavage and tail vein injection.Results: Sphere-shaped HAP is more likely to adsorb onto platelet surfaces, while rod-shaped HAP is more likely to cause hemolysis. Although there are differences in the in vitro experimental results between sphere-shaped HAP and rod-shaped HAP, both types demonstrate good blood compatibility at a 20 mM concentration. Furthermore, in vivo experiments showed that sphere-shaped nano-HAP induced a more pronounced increase in white blood cell count, suggesting that it may exhibit greater toxicity.Conclusion: While differences exist in the blood compatibility test results between the two HAPs, these differences are minimal, with both results falling within a safe range. Overall, HAP demonstrates excellent blood compatibility.

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In vitro/In vivo Evaluations of Hydroxyapatite Nanoparticles with Different Geometry.

Purpose: Hydroxyapatite-based nanoparticles have found diverse applications in drug delivery, gene carriers, diagnostics, bioimaging and tissue engineering, owing to their ability to easily enter the bloodstream and target specific sites. However, there is limited understanding of the potential adverse effects and molecular mechanisms of these nanoparticles with varying geometries upon their entry into the bloodstream. Here, we used two commercially available hydroxyapatite nanoparticles (HANPs) with different geometries (less than 100 nm in size each) to investigate this issue. Methods: First, the particle size, Zeta potential, and surface morphology of nano-hydroxyapatite were characterized. Subsequently, the effects of 2~2000 µM nano-hydroxyapatite on the proliferation, migration, cell cycle distribution, and apoptosis levels of umbilical vein endothelial cells were evaluated. Additionally, the impact of nanoparticles of various shapes on the differential expression of genes was investigated using transcriptome sequencing. Additionally, we investigated the in vivo biocompatibility of HANPs through gavage administration of nanohydroxyapatite in mice. Results: Our results demonstrate that while rod-shaped HANPs promote proliferation in Human Umbilical Vein Endothelial Cell (HUVEC) monolayers at 200 µM, sphere-shaped HANPs exhibit significant toxicity to these monolayers at the same concentration, inducing apoptosis/necrosis and S-phase cell cycle arrest through inflammation. Additionally, sphere-shaped HANPs enhance SULT1A3 levels relative to rod-shaped HANPs, facilitating chemical carcinogenesis-DNA adduct signaling pathways in HUVEC monolayers. In vivo experiments have shown that while HANPs can influence the number of blood cells and comprehensive metabolic indicators in blood, they do not exhibit significant toxicity. Conclusion: In conclusion, this study has demonstrated that the geometry and surface area of HANPs significantly affect VEC survival status and proliferation. These findings hold significant implications for the optimization of biomaterials in cell engineering applications.

Population dynamics in spatial suppression gene drive models and the effect of resistance, density dependence, and life history.

Due to their super-Mendelian inheritance, gene drive systems have the potential to provide revolutionary solutions to critical public health and environmental problems. For suppression drives, however, spatial structure can cause "chasing" population dynamics that may postpone target population elimination or even cause the drive to fail. In chasing, wild-type individuals elude the drive and recolonize previously suppressed areas. The drive can re-enter these recolonized areas, but often is not able to catch up to wild-type and finally eliminate it. Previous methods for chasing detection are only suitable to limited parameter ranges. In this study with expanded parameter ranges, we found that the shift from chasing dynamics to static equilibrium outcomes is continuous as drive performance is reduced. To quantify this, we defined a Weighted Average Nearest Neighbor statistic to assess the clustering degree during chasing, while also characterizing chasing by the per-generation chance of population elimination and drive loss. To detect chasing dynamics in local areas and to detect the start of chasing, we implemented Density-Based Spatial Clustering of Applications with Noise. Using these techniques, we determined the effect of arena size, resistance allele formation rate in both the germline and in the early embryo from maternally deposited Cas9, life history and reproduction strategies, and density-dependent growth curve shape on chasing outcomes. We found that larger real-world areas will be much more vulnerable to chasing and that species with overlapping generations, fecundity-based density dependence, and concave density-dependent growth curves have smaller and more clustered local chasing with a greater chance of eventual population elimination. We also found that embryo resistance and germline resistance hinder drive performance in different ways. These considerations will be important for determining the necessary drive performance parameters needed for success in different species, and whether future drives could potentially be considered as release candidates.

A biomimetic hyaluronic acid-silk fibroin nanofiber scaffold promoting regeneration of transected urothelium.

This study was designed to investigate the regulatory effect of hyaluronic acid (HA)-coating silk fibroin (SF) nanofibers during epithelialization of urinary tract for urethral regeneration. The obtained electrospun biomimetic tubular HA-SF nanofiber scaffold is composed of a dense inner layer and a porous outer layer in order to mimic adhesion and cavernous layers of the native tissue, respectively. A thin layer of HA-gel coating was fixed in the inner wall to provide SF nanofibers with a dense and smooth surface nano-topography and higher hydrophilicity. Compared with pure SF nanofibers, HA-SF nanofibers significantly promoted the adhesion, growth, and proliferation of primary urothelial cells, and up-regulate the expression of uroplakin-3 (terminal differentiation keratin protein in urothelium). Using the New Zealand male rabbit urethral injury model, the scaffold composed of tubular HA-SF nanofibers could recruit lumen and myoepithelial cells from the adjacent area of the host, rapidly reconstructing the urothelial barrier in the wound area in order to keep the urinary tract unobstructed, thereby promoting luminal epithelialization, smooth muscle bundle structural remodeling, and capillary formation. Overall, the synergistic effects of nano-topography and biophysical cues in a biomimetic scaffold design for effective endogenous regeneration.

MutiLoc Nail Versus Philos Plate in Treating Proximal Humeral Fractures: A Retrospective Study Among the Alderly.

BACKGROUND: Proximal humeral fractures (PHFs) account for 4-5% of all fractures in the elderly. There is still a controversy among the treatments in the displaced PHFs. Our aim was to explore the clinical outcome of PHFs with the treatment of MultiLoc nail or Philos plate in the elderly patients. METHODS: A total of 82 sustained elderly patients with PHFs were finally recruited between Dec 2016 and Dec 2017. 34 patients were treated with MultiLoc nail and 48 patients were treated with Philos plate. The demographics, fracture types, blood loss, operation time, union time, postoperative complications, visual analog scores (VASs), Constant scores, American Shoulder and Elbow Scores (ASESs), and neck-shaft-angle (NSA) between the two groups were compared. RESULTS: No differences were observed in the demographics, fracture types, VAS, Constant scores, and ASES scores between the two groups at final follow-up. Compared with the plate group, the blood loss, operation time, and union time were significantly lower in the nail group (all P < .05). The rate of general complications was 54.17% in the plate group, which was higher than that in the nail group (26.47%, P = .01). Three patients experienced reoperation in the plate group (3/48; 6.25%), but none in the nail group. Although there were no significant differences in intraoperative NSA between the two groups, the NSA at final follow-up in the nail group was much higher than the plate group (137.55 ± 5.53°vs 134.47 ± 5.92°, P = .02). CONCLUSIONS: Multiloc intramedullary nail showed the similar effectiveness of final VAS, final Constant scores, and ASES scores in PHFs treatment with Philos plate. However, MultiLoc nail is superior to Philos plate in blood loss, operation time, complications, reoperation rate, and the change of NSA.

Complications associated with hyperextension bicondylar tibial plateau fractures: a retrospective study.

BACKGROUND: Hyperextension bicondylar tibial plateau fracture (HBTPF) is a particular form of tibial plateau fracture which has gained increasing interest recently but were rarely documented. In this study, we reported the characteristics, clinical intervention, and therapeutic outcomes of HBTPF patients. METHODS: From May 2015 to October 2017, clinical data of consecutive patients with bicondylar tibial plateau fractures (BTPF) who underwent surgical treatment in our hospital were retrospectively studied. The patients were allocated to either the HBTPF group (study group) or the non-HBTPF group (control group) based on the radiological features, and inclusion and exclusion criteria. Demographics, characteristics of knee joint injuries, complications, and outcomes were compared between the two groups. RESULTS: In total, 59 patients were included in this study. Among them, 17 patients with HBTPF were identified and 42 patients were diagnosed as non-HBTPF. No differences in age, sex, cause of injury, side of injury, site of injury, nerve injury, operation time, and treatment time and incision complication between HBTPF and non-HBTPF group. The incidence rate of popliteal artery injury in HBTPF group was 29.4 %, which was significantly higher than that of non-HBTPF group. Small bone chips on the lateral film were found in 94.1 % of the patients in HBTPF group, which was significantly higher than that of non-HBTPF group. The range of motion (ROM) and hospital for special surgery (HSS) score of HBTPF group were significantly lower than those of non-HBTPF group. CONCLUSIONS: HBTPF is a severe injury with a higher incidence rate of popliteal artery injury and worse outcomes than non-HBTPF. Small bone chips at the anterior margin of the proximal tibia on the lateral plain film might be a characteristic of HBTPF.