Lanthanides-Substituted Hydroxyapatite/Aloe vera Composite Coated Titanium Plate for Bone Tissue Regeneration.

PURPOSE: To develop the surface-treated metal implant with highly encouraged positive properties, including high anti-corrosiveness, bio-activeness and bio-compatibleness for orthopedic applications. METHODS: In this work, the surface of commercially pure titanium (Ti) metal was treated with bio-compatible polydopamine (PD) by merely immersing the Ti plate in PD solution. The composite of trivalent lanthanide minerals (La3+, Ce3+ and Gd3+)-substituted hydroxyapatite (MHAP) with Aloe vera (AV) gel was prepared and coated on the PD-Ti plate by electrophoretic deposition (EPD) method. The choice of trivalent lanthanide ions is based on their bio-compatible nature and bone-seeking properties. The formation of the PD layer, composites, and composite coatings on Ti plate and PD-Ti surface was confirmed by FT-IR, XRD, SEM and HR-TEM observations. In-vitro assessments such as osteoblasts like MG-63 cell viability, alkaline phosphatase activity and mineralization ability of the MHAP/AV composite were tested, and the composite-coated plate was implanted into a rat bone defect model for in-vivo bone regeneration studies. RESULTS: The coating ability of the MHAP/AV composite was highly preferred to PD-treated Ti plate than an untreated Ti plate due to the metal absorption ability of PD. This was confirmed by SEM analysis. The in-vitro and in-vivo studies show the better osteogenic ability of MHAP/AV composite at 14th day and 4th week of an experimental period, respectively. CONCLUSION: The osteoblast ability of the fabricated device without producing any adverse effect in the rat model recommends that the fabricated device would serve as a better platform on the hard tissue regeneration for load-bearing applications of orthopedics.

A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts.

Dysregulated microRNAs in osteoclasts could cause many skeletal diseases. The therapeutic manipulation of these pathogenic microRNAs necessitates novel, efficient delivery systems to facilitate microRNAs modulators targeting osteoclasts with minimal off-target effects. Bone resorption surfaces characterized by highly crystallized hydroxyapatite are dominantly occupied by osteoclasts. Considering that the eight repeating sequences of aspartate (D-Asp8) could preferably bind to highly crystallized hydroxyapatite, we developed a targeting system by conjugating D-Asp8 peptide with liposome for delivering microRNA modulators specifically to bone resorption surfaces and subsequently encapsulated antagomir-148a (a microRNA modulator suppressing the osteoclastogenic miR-148a), i.e. (D-Asp8)-liposome-antagomir-148a. Our results demonstrated that D-Asp8 could facilitate the enrichment of antagomir-148a and the subsequent down-regulation of miR-148a in osteoclasts in vivo, resulting in reduced bone resorption and attenuated deterioration of trabecular architecture in osteoporotic mice. Mechanistically, the osteoclast-targeted delivery depended on the interaction between bone resorption surfaces and D-Asp8. No detectable liver and kidney toxicity was found in mice after single/multiple dose(s) treatment of (D-Asp8)-liposome-antagomir-148a. These results indicated that (D-Asp8)-liposome as a promising osteoclast-targeting delivery system could facilitate clinical translation of microRNA modulators in treating those osteoclast-dysfunction-induced skeletal diseases.