Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.     

The promotion of osteointegration under diabetic conditions using chitosan/hydroxyapatite composite coating on porous titanium surfaces

Composited Chitosan/Hydroxyapatite (CS/HA) material coated on titanium surface (cTi) is a promising approach to produce biomaterials with better osseointegration capacity, but its bio-performance under diabetic conditions and the mechanisms involved remain elusive. We propose that the alterations in the Wnt/β-catenin pathway may play a role in mediating the improvement effect of cTi on diabetes-induced impaired implant osteointegration. To confirm the hypothesis, primary rat osteoblasts incubated on Ti and cTi were subjected to normal serum (NS), diabetic serum (DS), DS + Wnt3a (a specific Wnt agonist) and DS + Dkk1 (a specific Wnt antagonist) treatment. In vivo study was performed on diabetic sheep implanted with Ti or cTi into the bone defect on crista iliaca. Results showed that diabetes depressed osteoblast function evidenced by impaired cell adhesion and morphology, decreased cell proliferation and ALP activity, and higher apoptotic rate on Ti. Importantly, both cTi and Wnt3a treatment ameliorated osteoblastic dysfunction and apoptosis under diabetic condition. Implantation with cTi significantly improved osteointegration evidenced by Micro-CT and histological examinations compared with Ti. Moreover, the aforementioned promotive effects afforded by cTi were abolished by blocking Wnt pathway with Dkk1. Our study explicitly demonstrates that CS/HA composite material improves diabetes-induced impaired osteointegration of Ti via the reactivation of Wnt/β-catenin pathway and provides a target point for biomaterial modification to attain better clinical performance in diabetic patients.     

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.     

通过自生长方式实现壳聚糖-胶原聚合物引导的牙体硬组织仿生再矿化

目的 以改良的壳聚糖、胶原等生物大分子作为矿化模板,引导釉质实现类似自生长的再矿化。方法 通过对天然聚阳离子多糖--壳聚糖进行磷酸化本体改性,生成其聚阴离子衍生物磷酸化壳聚糖;以京尼平为交联剂将磷酸化壳聚糖与聚阳离子的Ⅰ型胶原交联改性,构建双性聚电解质复合物水凝胶作为生物矿化的大分子模板,以紫外光辐射激发其在惰性牙体表面的化学组装,仿生唾液提供矿化离子,调控磷灰石晶体在牙体原位的形成与组装,生成羟磷灰石。结果 红外光谱检测证实,PO43−官能团（3 446 cm-1）成功引入壳聚糖,扫描电子显微镜下双性聚电解质复合物水凝胶呈现多孔并存,孔孔交通的级联结构。水凝胶原位接枝能够生成白色晶体,X射线衍射证实新生的晶体为羟磷灰石,该沉积层与原有釉质同质结合,类似釉柱平行排列;新生晶体直径30~60 nm,硬度接近牙本质。结论 取材容易、操作便利的双性聚离子凝胶能够在一定程度上模仿釉质矿化模板,实现羟磷灰石的自生长,这对釉质结构仿生的发展有重要意义。     

基于增材制造技术修复缺损颅骨的研究和应用

该文运用增材制造技术快速制备三维重建的缺损颅骨植入体,通过对骨植入体材料对比分析,选择多孔羟基磷灰石材料应用于颅骨植入手术中。运用Mimics 10.0软件对临床计算机断层扫描(CT)影像数据重建三维植人体模型,采用增材制造技术制备多孔羟基磷灰石颅骨植入体,与颅骨贴合度好,表面光滑平顺,而多孔羟基磷灰石能够引导和诱导骨的形成,大大提高其生物相容性。增材制造技术快速制备的特点促使个性化颅骨修补植入物成为可能,个性化医用三维模型用于植入手术降低手术风险,术后效果好,具有推广应用的前景。     

Clinical and radiographic evaluation of the efficacy of platelet-rich plasma combined with hydroxyapatite bone graft substitutes in the treatment of intra-bony defects in maxillofacial region

Objective. The aim of this study is to evaluate the efficacy of platelet-rich plasma (PRP) clinically and radiographically when combined with bovine derived hydroxyapatite (HA) bone grafting materials and resorbable collagen membranes for the treatment of intra-bony defects frequently seen at the distal aspect of mandibular second molars following the surgical extraction of fully impacted mandibular wisdom teeth. Study design. Eighteen patients were scheduled for post-operative visits at 1, 3 and 6 months post-operatively, probing depths were measured and digital panoramic radiographs were taken. Results. There were no significant differences on probing depths among two groups. Radiographic assessment also showed no significant difference among groups at 1st and 6th month intervals, while 3 months post-operatively the amount of radiographic density at the PRP side was significantly higher. Conclusion. Combined use of PRP and bovine-derived HA graft materials for the treatment of intra-bony defects might be an appropriate approach when the main goal is providing earlier bone regeneration.     

Treatment of sphenoid dysplasia with a titanium-reinforced porous polyethylene implant in orbitofrontal neurofibroma: Report of three cases

Orbital manifestations occur in less than 1% of patients with neurofibromatosis type 1 (NF1). These manifestations are frequently associated with sphenoid wing dysplasia. The typical radiologic feature is partial or total loss of the greater wing of the sphenoid bone, which leads to herniation of the temporal lobe through the orbital cavity resulting in proptosis and pulsating exophthalmos. Traditional reconstruction of this bone defect involves split bone grafting or titanium mesh. However, these techniques have some limitations due to bone resorption and infection risk. We report the use of 0.85 mm titanium-reinforced porous polyethylene implant sheet in three cases of orbital neurofibromatosis with sphenoid dysplasia. The role of this material was to create a barrier between the brain and orbital cavity. The implant sheet was modeled intraoperatively to reconstruct the orbital cavity anatomy and fitted without any screws. The malleability of the implant allows quick reconstruction of the curved orbital skeleton. Furthermore, the implant doesn't interfere with postoperative imaging and may decrease risk infection.     

Biological Advantages of Porous Hydroxyapatite Scaffold Made by Solid Freeform Fabrication for Bone Tissue Regeneration

Presently, commercially available porous bone substitutes are manufactured by the sacrificial template method, direct foaming method, and polymer replication method (PRM). However, current manufacturing methods provide only the simplest form of the bone scaffold and cannot easily control pore size. Recent developments in medical imaging technology, computer‐aided design, and solid freeform fabrication (SFF), have made it possible to accurately produce porous synthetic bone scaffolds to fit the defected bone shape. Porous scaffolds were fabricated by SFF and PRM for a comparison of physical and mechanical properties of scaffold. The suggested three‐dimensional model has interconnected cubic pores of 500 μm and its calculated porosity is 25%. Whereas hydroxyapatite scaffolds fabricated by SFF had connective macropores, those by PRM formed a closed pore external surface with internally interconnected pores. SFF was supposed to be a proper method for fabricating an interconnected macroporous network. Biocompatibility was confirmed by testing the cytotoxicity, hemolysis, irritation, sensitization, and implantation. In summary, the aim was to verify the safety and efficacy of the scaffolds by biomechanical and biological tests with the hope that this research could promote the feasibility of using the scaffolds as a bone substitute.     

Bone response to free form-fabricated hydroxyapatite and zirconia scaffolds: a histological study in the human maxilla

Objectives: Synthetic and biological materials are increasingly used to provide temporary or permanent scaffolds for bone regeneration. This study evaluated the effect of material chemistry and microporosity on bone ingrowth and osseointegration of zirconia (ZrO₂) and hydroxyapatite (HA) scaffolds in the human maxilla.
Material and methods: Twelve patients subjected to dental implant placement were enrolled in the study. Scaffolds of ZrO₂ and HA were placed in the maxilla of each subject, using a randomization protocol. After 3 months of healing, biopsies were harvested comprising the scaffolds and surrounding bone tissue. The biopsies were processed for histological evaluation and morphometric analysis (bone ingrowth and bone-to-scaffold contact).
Results: Healing was uneventful in all cases. All scaffolds demonstrated a measurable bone response using light microscopy and scanning electron microscopy. Microporous HA scaffolds revealed four times larger bone ingrowth and seven times larger bone contact as compared with ZrO₂ scaffolds.
Conclusion: The results show that chemistry and microporosity of HA promote bone ingrowth and bone contact of ceramic scaffolds in human maxilla.     

Metal Phosphate-Supported Pt Catalysts for CO Oxidation

Oxides (such as SiO₂, TiO₂, ZrO₂, Al₂O₃, Fe₂O₃, CeO₂) have often been used to prepare supported Pt catalysts for CO oxidation and other reactions, whereas metal phosphate-supported Pt catalysts for CO oxidation were rarely reported. Metal phosphates are a family of metal salts with high thermal stability and acid-base properties. Hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, denoted as Ca-P-O here) also has rich hydroxyls. Here we report a series of metal phosphate-supported Pt (Pt/M-P-O, M = Mg, Al, Ca, Fe, Co, Zn, La) catalysts for CO oxidation. Pt/Ca-P-O shows the highest activity. Relevant characterization was conducted using N₂ adsorption-desorption, inductively coupled plasma (ICP) atomic emission spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), CO₂ temperature-programmed desorption (CO₂-TPD), X-ray photoelectron spectroscopy (XPS), and H₂ temperature-programmed reduction (H₂-TPR). This work furnishes a new catalyst system for CO oxidation and other possible reactions.