Interface Between Titanium Miniplate/Screw and Human Calvaria

This study demonstrates interfacial changes of titanium miniplate/screw with normal calvaria and nonvascularized calvarial bone graft ensued from craniectomy in a 53-year-old female. In 18 months after operation, a right parietal bone containing an L-shaped miniplate with screws, 5mm long and 2mm in external diameter, was harvested, fixed, and embedded in methylmetacrylate. Fifteen micrometer thick sections were made by an EXAKT cutting-grinding system (Exakt Company, Hamburg, Germany), and reviewed under the bright field light microscope. The mean of the bonecontacting surface ratio (BCSR) in six screwed bone was 64.1%; 69.3% in normal bone, and 60.4% in grafted bone. The trabecular bone areas in 10x5mm (50mm2) rectangular area of diploe surrounding the screws was 43.02mm2; 45.25mm2 in normal calvaria; and 41.82mm2 in grafted bone. The mean Ca/P peak-height ratio of the plated and screwed calvaria was 1.47 in a 9mm wide zone around each screw; 1.37 in normal calvaria; and 1.51 in grafted calvaria. We concede that the effect of direct contact of titanium with screws onto the bone is as much as an osseous integration (osseointegration)

Recombinant Human Bone Morphogenetic Protein-2 and Collagen for Bone Regeneration

The study reported describes a combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) and collagen (C) to regenerate bone. Unilateral critical-sized defects (CSDs) were prepared in radii of 32 skeletally mature New Zealand white rabbits. Rabbits were divided evenly among four treatments: autograft, absorbable C (Helistatt), 35 mg of rhBMP-2 combined with absorbable C (rhBMP-2/C), and untreated CSDs. The two euthanasia periods were 4 and 8 weeks. Radiographs were taken the day of surgery, every 2 weeks, and at term and the percent of radiopacity was measured. Data analysis revealed a time-dependent increase in the percent radiopacity with rhBMP-2/C. Histological examination revealed the rhBMP-2/C treatment regenerated osseous contour by 8 weeks. According to quantitative histomorphometry, the CSD and C groups had significantly less new bone than either autograft or rhBMP-2/C (p ¡ 0.05). The results suggest that rhBMP-2/C could be an effective therapy to restore segmental bone defects

Preclinical Toxicology Studies of Recombinant Human Platelet-Derived Growth Factor-BB Either Alone or in Combination with Beta-Tricalcium Phosphate and Type I Collagen

Human platelet-derived growth factor-BB (hPDGF-BB) is a basic polypeptide growth factor released from platelets at the injury site. It is a multifunctional molecule that regulates DNA synthesis and cell division and induces biological effects that are implicated in tissue repair, atherosclerosis, inflammatory responses, and neoplastic diseases. This paper is an overview of the toxicology data generated from a broad testing platform to determine bone, soft tissue, and systemic responses following administration of rhPDGF-BB. Moreover, the systemic and local toxicity of recombinant human PDGF-BB (rhPDGF-BB) in combination with either beta-tricalcium phosphate (β-TCP) or collagen combined with β-TCP was studied to determine dermal sensitization, irritation, intramuscular tissue responses, pyrogenicity, genotoxicity, and hemolytic properties. All data strongly suggest that rhPDGF-BB either alone or in combination with β-TCP or collagen with β-TCP is biocompatible and has neither systemic nor local toxicity, supporting its safe use in enhancing wound healing in patients

Semiconductor-based DNA sequencing of histone modification states

The recent development of a semiconductor-based, non-optical DNA sequencing technology promises scalable, low-cost and rapid sequence data production. The technology has previously been applied mainly to genomic sequencing and targeted re-sequencing. Here we demonstrate the utility of Ion Torrent semiconductor-based sequencing for sensitive, efficient and rapid chromatin immunoprecipitation followed by sequencing (ChIP-seq) through the application of sample preparation methods that are optimized for ChIP-seq on the Ion Torrent platform. We leverage this method for epigenetic profiling of tumour tissues

In Vivo GFP Knockdown by Cationic Nanogel-siRNA Polyplexes

RNA interference (RNAi) is a powerful tool to treat diseases and elucidate target gene function. Prior to clinical implementation, however, challenges including the safe, efficient and targeted delivery of siRNA must be addressed. Here, we report cationic nanogel nanostructured polymers (NSPs) prepared by atom transfer radical polymerization (ATRP) for in vitro and in vivo siRNA delivery in mammalian models. Outcomes from siRNA protection studies suggested that nanogel NSPs reduce enzymatic degradation of siRNA within polyplexes. Further, the methylation of siRNA may enhance nuclease resistance without compromising gene knockdown potency. NSP-mediated RNAi treatments against Gapdh significantly reduced GAPDH enzyme activity in mammalian cell culture models supplemented with 10% serum. Moreover, nanogel NSP-mediated siRNA delivery significantly inhibited in vivo GFP expression in a mouse model. GFP knockdown was siRNA sequence-dependent and facilitated by nanogel NSP carriers. Continued testing of NSP/siRNA compositions in disease models may produce important new therapeutic options for patient care

Synthesis of Poly(meth)acrylates with Thioether and Tertiary Sulfonium Groups by ARGET ATRP and Their Use as siRNA Delivery Agents

The field of RNA interference depends on the development of safe and efficient carriers for short interfering ribonucleic acid (siRNA) delivery. Conventional cationic monomers for siRNA delivery have utilized the nitrogen heteroatom to produce cationic charges. Here, we polymerized cationic sulfonium (meth)­acrylate by activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to form polymers with narrow molecular weight distributions for siRNA delivery. The tertiary sulfonium species was stable toward dealkylation in water but less stable in the polar aprotic solvent dimethyl sulfoxide. Block copolymers poly­(ethylene oxide) with poly­(meth)­acrylate containing sulfonium moieties were prepared as an siRNA delivery platform. Results suggested block copolymers were biocompatible up to 50 μg/mL <i>in vitro</i> and formed polyplexes with siRNA. Additionally, block copolymers protected siRNAs against endonuclease digestion and facilitated knockdown of glyceraldehyde 3-phosphate dehydrogenase (<i>Gapdh</i>) mRNA expression in murine calvarial preosteoblasts. The versatility, biocompatibility, and cationic nature of these tertiary sulfonium groups are expected to find widespread biological applications