A Combination of Guanidyl and Phenyl Groups on a Dendrimer Enables Efficient siRNA and DNA Delivery

Gene therapy has received considerable attention due to its great potential in the treatment of various diseases; however, the design of efficient and biocompatible carriers for the delivery of siRNA as well as DNA still remains a major challenge. In this study, we developed an efficient carrier for gene delivery by modification of a compound containing both guanidyl and phenyl groups on the surface of a cationic dendrimer. The guanidyl group on the dendrimer facilitates nucleic acid condensation via specific guanidinium–phosphate interactions, whereas the phenyl group on the polymer is critical for efficient endosomal escape. The combination of guanidyl and phenyl shows a synergistic effect in facilitated endocytosis. The designed material is much more efficient in siRNA and DNA delivery than control materials such as dendrimers engineered with a guanidyl or phenyl group only, as well as intact dendrimers, and shows comparable efficacy to commercial transfection reagent Lipofectamine 2000. In addition, the material and its complex with nucleic acid show minimal toxicity on the transfected cells. This study provides a new strategy to develop multifunctional polymers for efficient siRNA and DNA delivery

The surgical sites where the screws were placed.

<p>The surgical sites where the screws were placed.</p

Histological sections of smooth surface (SS) (A, C and E) and roughened surface (RS) (B, D and F) screws at 6 weeks.

<p>Fibrous tissue formation can be seen around the screws, as indicated by the red arrow. Black arrows indicate the bone tissue.</p

(A) Stiffness and (B) angle-related stiffness at 6 (group A) and 12 weeks (group B).

<p>(A) Stiffness and (B) angle-related stiffness at 6 (group A) and 12 weeks (group B).</p

Mechanical testing results of pullout tests and torsion tests (mean±SD).

<p>*For the maximum pullout strength and stiffness, significant difference was observed between SS and RS in the same group, and for the maximum torque and angle-related stiffness, there was significant difference between the two groups at either time point.</p

Figure 1

<p>(A) Conventional titanium alloy screw with a smooth surface (SS). (B) Titanium alloy screws with a roughened surface (RS) were fabricated by electron beam melting (EBM).</p

Scanning electron microscopy image of the broken end of roughened surface (RS) screw; each layer of the melted Ti6Al4V (No 1–4) and the broken end (black arrow) can be observed clearly.

<p>Scanning electron microscopy image of the broken end of roughened surface (RS) screw; each layer of the melted Ti6Al4V (No 1–4) and the broken end (black arrow) can be observed clearly.</p

ROI parameters of the SS and the RS screws (mean±SD).

<p>BV/TV: Bone volume/Total volume; BS/BV: Bone surface area/Bone volume; Tb.Th: Trabecular thickness. Tb.N: Trabecular number.</p

Histological sections of smooth surface (SS) (A, C and E) and roughened surface (RS) (B, D and F) screws at 12 weeks.

<p>Fibrous tissue, which was evident at 6 weeks, had almost disappeared by this timepoint. Black arrows indicate that the bone tissue integrates with the screws and grows into the gaps of the RS.</p

Tailored Surface Treatment of 3D Printed Porous Ti6Al4V by Microarc Oxidation for Enhanced Osseointegration via Optimized Bone In-Growth Patterns and Interlocked Bone/Implant Interface

3D printed porous titanium (Ti) holds enormous potential for load-bearing orthopedic applications. Although the 3D printing technique has good control over the macro-sturctures of porous Ti, the surface properties that affect tissue response are beyond its control, adding the need for tailored surface treatment to improve its osseointegration capacity. Here, the one step microarc oxidation (MAO) process was applied to a 3D printed porous Ti6Al4V (Ti64) scaffold to endow the scaffold with a homogeneous layer of microporous TiO₂ and significant amounts of amorphous calcium-phosphate. Following the treatment, the porous Ti64 scaffolds exhibited a drastically improved apatite forming ability, cyto-compatibility, and alkaline phosphatase activity. In vivo test in a rabbit model showed that the bone in-growth at the untreated scaffold was in a pattern of distance osteogenesis by which bone formed only at the periphery of the scaffold. In contrast, the bone in-growth at the MAO-treated scaffold exhibited a pattern of contact osteogenesis by which bone formed in situ on the entire surface of the scaffold. This pattern of bone in-growth significantly increased bone formation both in and around the scaffold possibly through enhancement of bone formation and disruption of bone remodeling. Moreover, the implant surface of the MAO-treated scaffold interlocked with the bone tissues through the fabricated microporous topographies to generate a stronger bone/implant interface. The increased osteoinetegration strength was further proven by a push out test. MAO exhibits a high efficiency in the enhancement of osteointegration of porous Ti64 via optimizing the patterns of bone in-growth and bone/implant interlocking. Therefore, post-treatment of 3D printed porous Ti64 with MAO technology might open up several possibilities for the development of bioactive customized implants in orthopedic applications