Synergistic effect of drug/antibiotic-impregnated micro/nanohybrid mesoporous bioactive glass/calcium phosphate composite bone cement on antibacterial and osteoconductive activities.

Calcium phosphate bone cements (CPC) can be used in minimally invasive surgery because of their injectability, and they can also be used to repair small and irregular bone defects. This study aimed to release the antibiotic gentamicin sulfate (Genta) to reduce tissue inflammation and prevent infection in the early stages of bone recovery. Subsequently, the sustained release of the bone-promoting drug ferulic acid (FA) mimicked the response of osteoprogenitor D1 cells interaction, thereby accelerating the healing process of the overall bone repair. Accordingly, the different particle properties of micro-nano hybrid mesoporous bioactive glass (MBG), namely, micro-sized MBG (mMBG) and nano-sized MBG (nMBG), were explored separately to generate different dose releases in MBG/CPC composite bone cement. Results show that nMBG had better sustained-release ability than mMBG when impregnated with the same dose. When 10 wt% of mMBG hybrid nMBG and composite CPC were used, the amount of MBG slightly shortened the working/setting time and lowered the strength but did not hinder the biocompatibility, injectability, anti-disintegration, and phase transformation of the composite bone cement. Furthermore, compared with 2.5wt%Genta@mMBG/7.5 wt% FA@nMBG/CPC, 5wt.%Genta@mMBG/5wt.%FA@nMBG/CPC exhibited better antibacterial activity, better compressive strength, stronger mineralization of osteoprogenitor cell, and similar 14-day slow-release trend of FA. The MBG/CPC composite bone cement developed can be used in clinical surgery to achieve the synergistic sustained release of antibacterial and osteoconductive activities.

Chemical cross-linking on gelatin-hyaluronan loaded with hinokitiol for the preparation of guided tissue regeneration hydrogel membranes with antibacterial and biocompatible properties.

The mechanical properties and structural stability of hydrogels and their performance in antidegradation can be enhanced by cross-linking them with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). However, residual EDC compromises the biocompatibility of cross-linked hydrogels and the formability of un-cross-linked hydrogels. In this study, a facile process for preparing hydrogel regenerative membranes exerting antibacterial effects and containing gelatin/hyaluronic acid (G/HA) through solution casting was proposed. The membranes were cross-linked with EDC (G/HA-Ec-0H) and impregnated with two concentrations of the antibacterial agent of hinokitiol (G/HA-Ec-2H and G/HA-Ec-4H). Amide bonds formed, and the rate of active amino acid fixation was higher than 90%, which was directly proportional to the degree of cross-linking. The G/HA-Ec-2H and G/HA-Ec-4H groups with hinokitiol showed good antibacterial properties. The rate of hydrogel degradation decreased, and the integrity of sample morphology was maintained at more than 80% for over 3 days in the immersion. Then, the hydrogel structures relaxed and disintegrated through a rapid degradation reaction within 24 h. The biocompatibility results showed that low concentrations of hinokitiol did not affect cell viability. Moreover, hydrogel membranes after 14 days of cell incubation showed good cell adhesion and proliferation. In summary, the membrane biostability of the cross-linked gelatin/hyaluronan hydrogels was enhanced by EDC at a biocompatible concentration, and the functionalized group of G/HA-Ec-2H shows potential as a biodegradable material for biocompatible tissue-guarded regeneration membranes with antibacterial properties.

Osteoregenerative capacities of dicalcium phosphate-rich calcium phosphate bone cement.

Calcium phosphate cement (CPC) is a widely used bone substitute. However, CPC application is limited by poor bioresorption, which is attributed to apatite, the stable product. This study aims to systematically survey the biological performance of dicalcium phosphate (DCP)-rich CPC. DCP-rich CPC exhibited a twofold, surface-modified DCP anhydrous (DCPA)-to-tetracalcium phosphate (TTCP) molar ratio, whereas conventional CPC (c-CPC) showed a onefold, surface unmodified DCPA-to-TTCP molar ratio. Cell adhesion, morphology, viability, and alkaline phosphatase (ALP) activity in the two CPCs were examined with bone cell progenitor D1 cultured in vitro. Microcomputed tomography and histological observation were conducted after CPC implantation in vivo to analyze the residual implant ratio and new bone formation rate. D1 cells cultured on DCP-rich CPC surfaces exhibited higher cell viability, ALP activity, and ALP quantity than c-CPC. Histological evaluation indicated that DCP-rich CPC showed lesser residual implant and higher new bone formation rate than c-CPC. Therefore, DCP-rich CPC can improve bioresorption. The newly developed DCP-rich CPC exhibited potential therapeutic applications for bone reconstruction.

Biphasic products of dicalcium phosphate-rich cement with injectability and nondispersibility.

In this study, a calcium phosphate cement was developed using tetracalcium phosphate and surface-modified dicalcium phosphate anhydrous (DCPA). This developed injectable bone graft substitute can be molded to the shape of the bone cavity and set in situ through the piping system that has an adequate mechanical strength, non-dispersibility, and biocompatibility. The materials were based on the modified DCPA compositions of calcium phosphate cement (CPC), where the phase ratio of the surface-modified DCPA is higher than that of the conventional CPC for forming dicalcium phosphate (DCP)-rich cement. The composition and morphology of several calcium phosphate cement specimens during setting were analyzed via X-ray diffractometry and transmission electron microscopy coupled with an energy dispersive spectroscopy system. The compressive strength of DCP-rich CPCs was greater than 30MPa after 24h of immersion in vitro. The reaction of the CPCs produced steady final biphasic products of DCPs with apatite. The composites of calcium phosphate cements derived from tetracalcium phosphate mixed with surface-modified DCPA exhibited excellent mechanical properties, injectability, and interlocking forces between particles, and they also featured nondispersive behavior when immersed in a physiological solution.

Properties of osteoconductive biomaterials: calcium phosphate cement with different ratios of platelet-rich plasma as identifiers.

This study aims to evaluate further the performance of a platelet-rich plasma (PRP) additive incorporated with calcium phosphate bone cement (CPC) in vitro to prove its efficiency as bone graft substitutes and its compatibility to be incorporated into the CPC with other techniques in clinical restoration in vivo. The growth factor release ability and the osteogenic evaluation of PRP, CPC, and PRP/CPC testing groups with 5, 10, and 15 wt.% PRP were compared in vitro. Four groups were measured using non-decalcified staining methods in vivo, which include the testing group of 10 wt.% PRP/CPC selected from the evaluation in vitro, by using both the autograft with rabbit trabecular and CPC-only as comparison groups and the group without grafting material as the control sample. The results obtained through specimen immersion show that growth factor release and alkaline phosphatase activities after osteoprogenitor cell culture had a significantly better effect on 10 and 15 wt.% PRP/CPC than on the other groups in vitro. Analysis results suggest that PRP was still retained in the CPC matrix even after 32 days of immersion. The results in vivo show that the histology of the autograft bone and the control group without grafting material exhibited fibrous connective and adipose tissues, which obviously filled the created cavity even at nine weeks after the operation. Osteoregeneration was more successful in the PRP-additive group, which accumulated bone remodeling than in the other groups. In conclusion, CPC could be a potential carrier with adequate PRP additives that bear a therapeutic potential for enhanced bone tissue regeneration.

Calcium phosphate bone cement with 10 wt% platelet-rich plasma in vitro and in vivo.

OBJECTIVES: The aim of this study was to evaluate the performance of a 10 wt% platelet-rich plasma (PRP) additive composite with calcium phosphate cement (CPC) in vitro and in vivo. METHODS: The in vitro testing of modulus, the apatite conversion rate, morphology, cell and alkaline phosphatase (ALP) activities, and in vivo testing of histological examinations between two groups of 10 wt% PRP/CPC and CPC were characterised and compared. RESULTS: Although the crystallite morphologies showed a retarded effect in the PRP/CPC group in vitro, the modulus results showed that the 10 wt% PRP/CPC group had a significant reduction in strength but had no significant changes in the relative conversion ratio of the apatite phase with CPC only. The osteogenic evaluation of ALP expression was significantly increased by the PRP additives group with stem cells (D1) cultured for different periods (2-32 days). Our histological examinations showed that greater remodelling and the phenomenon of isolated/detached CPC particles were significantly observed at 9 weeks after implantation when the 10 wt% PRP/CPC composite was used. CONCLUSION: The results demonstrate that CPC may be a potential candidate as a carrier with PRP additives for bone regeneration.