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An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1455-1464, 2015. [ABSTRACT FROM AUTHOR]

Porous carbon fiber felts (PCFFs) have great applications in orthopedic surgery because of the strong mechanical strength, low density, high stability, and porous structure, but they are biologically inert. To improve their biological properties, we developed, for the first time, the hydroxyapatite (HA)/chitosan/carbon porous scaffolds (HCCPs). HA/chitosan nanohybrid coatings have been fabricated on PCFFs according to the following stages: (i) deposition of chitosan/calcium phosphate precursors on PCFFs; and (ii) hydrothermal transformation of the calcium phosphate precursors in chitosan matrix into HA nanocrystals. The scanning electron microscopy images indicate that PCFFs are uniformly covered with elongated HA nanoplates and chitosan, and the macropores in PCFFs still remain. Interestingly, the calcium-deficient HA crystals exist as plate-like shapes with thickness of 10-18 nm, width of 30-40 nm, and length of 80-120 nm, which are similar to the biological apatite. The HA in HCCPs is similar to the mineral of natural bone in chemical composition, crystallinity, and morphology. As compared with PCFFs, HCCPs exhibit higher in vitro bioactivity and biocompatibility because of the presence of the HA/chitosan nanohybrid coatings. HCCPs not only promote the formation of bone-like apatite in simulated body fluid, but also improve the adhesion, spreading, and proliferation of human bone marrow stromal cells. Hence, HCCPs have great potentials as scaffold materials for bone tissue engineering and implantation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1740-1748, 2014. [ABSTRACT FROM AUTHOR]

In order to improve the biocompatibility of metallic implants, bioactive components are often used as coatings so that a real bond with the surrounding bone tissue can be formed. We prepared ethyl cellulose/carbonated hydroxyapatite composite coatings (ECHCs) on Ti6Al4V substrates with carbonated hydroxyapatite coatings (CHACs) without ethyl cellulose as controls. The inorganic constituent on the CHACs and ECHCs is calcium-deficient carbonated hydroxyapatite with a flaky texture and a low degree of crystallinity. The flaky carbonated hydroxyapatite plates aggregate to form macropores with an aperture size of around 0.5-2.0 μm. The presence of ethyl cellulose provides superior morphology, contact angle, and biocompatibility characteristics. In comparison to CHACs, ECHCs exhibit a smoother, crack-free surface because the cracks are filled by ethyl cellulose. Moreover, the contact angle of ECHCs is 37.3°, greater than that of CHACs (13.0°). Surface biocompatibility was investigated by using human bone mesenchymal stem cells (hBMSCs). The attachment, spreadability, viability and proliferation of hBMSCs on ECHCs are superior to those on CHACs. Thus, the crack-free ECHCs have excellent biocompatibility and are appropriate for use as biological implants. [ABSTRACT FROM AUTHOR]

The bone graft-associated infection is widely considered in orthopedic surgery, which may lead to implant failure, extensive bone debridement, and increased patient morbidity. In this study, we fabricated ZSM-5 zeolites for drug delivery systems by hydrothermal method. The structure, morphology, biocompatibility, drug delivery property, and bactericidal property of the ZSM-5 zeolites were investigated. The ZSM-5 zeolites have mordenite framework inverted-type structure and exhibit the disk-like shape with the diameter of ∼350 nm and thickness of ∼165 nm. The biocompatibility tests indicate that human bone marrow stromal cells spread out well on the surfaces of the ZSM-5 zeolites and proliferate significantly with increasing culture time. As compared with the conventional hydroxyapatite particles, the ZSM-5 zeolites possess greater drug loading efficiency and drug sustained release property because of the ordered micropores, large Brunauer-Emmett-Teller (BET) surface areas, and functional groups. For the gentamicin-loaded ZSM-5 zeolites, the sustained release of gentamicin minimizes significantly bacterial adhesion and prevents biofilm formation against Staphylococcus epidermidis. The excellent biocompatibility, drug delivery property, and bactericidal property of the ZSM-5 zeolites suggest that they have great application potentials for treating implant-associated infections. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 583-591, 2014. [ABSTRACT FROM AUTHOR]

Implant-associated infection remains a difficult medical problem in orthopaedic surgery. Here, we report on the fabrication of gentamicin-loaded mesoporous bioactive glass (Gent-MBG) for use as a controlled antibiotic delivery system to achieve the sustained release of antibiotics in the local sites of bone defects. The high surface area and mesoporous structure of MBG enable higher drug loading efficiency (79-83 %) than non-mesoporous biological glass (NBG) (18-19 %). Gent-MBG exhibits sustained drug release for more than 6 days, and this controlled release of gentamicin significantly inhibits bacterial adhesion and prevents biofilm formation by S. aureus (ATCC25923) and S. epidermidis (ATCC35984). Biocompatibility tests with human bone marrow stromal cells (hBMSCs) indicate that MBG has better biocompatibility than NBG. Therefore, Gent-MBG can be used as a controlled drug delivery system to prevent and/or treat orthopedic peri-implant infections. [ABSTRACT FROM AUTHOR]

Abstract: Mesoporous titania coatings (MTCs) with a pore size of 4.75nm were prepared on Ti6Al4V substrates by a sol–gel process, and then irradiated with UV light at room temperature for 2h. The effects of mesoporous structure and UV irradiation on the in vitro bioactivity were investigated. Simulated body fluid (SBF) tests reveal that the MTCs exhibit a high apatite-forming ability, which may be attributed to the following reasons: (i) the BET surface area of the MTCs is ∼190m2/g, resulting in a greater density of Ti–OH groups than that without mesoporous structure; (ii) theoretical analysis reveals that the mesoporous structure can improve the driving force and nucleation rate of apatite precipitation in SBF. As compared with the MTCs, the UV-irradiated coatings do not exhibit any change in phase components and surface morphologies. However, the apatite-forming ability is higher on the UV irradiation coatings than on the MTCs because of the increase of Ti–OH groups and the improvement of wettability after UV irradiation. In addition, the investigation of the MG63 cell proliferation on the both substrates was performed. The results indicate that the MTCs before and after UV irradiation exhibit a good biocompatibility and are fit for the MG63 cell proliferation. [Copyright &y& Elsevier]

Postoperative implant-associated infection remains a serious complication in total joint arthroplasty (TJA) surgery. The addition of antibiotics to bone cement is used as an antimicrobial prophylaxis in cemented joint arthroplasty; however, in cementless arthroplasty, there are no comparable measures for the local delivery of antibiotics. In this study, a gentamicin-loaded Fe 3 O 4 /carbonated hydroxyapatite coating (Gent-MCHC) was fabricated according to the following steps: (i) deposition of Fe 3 O 4 /CaCO 3 particles on Ti6Al4V substrates by electrophoretic deposition; (ii) conversions of MCHC from Fe 3 O 4 /CaCO 3 coatings by chemical treatment; and (iii) formation of Gent-MCHC by loading gentamicin into MCHC. MCHC possessed mesoporous structure with a pore size of about 3.8 nm and magnetic property with the saturation magnetization strength of about 4.03 emu/g. Gent-MCHC had higher drug loading efficiency and drug release capacity, and superior biocompatibility and mitogenic activity than Ti6Al4V. Moreover, Gent-MCHC deterred bacterial adhesion and prevented biofilm formation. These results demonstrate that Gent-MCHC can be used as a local drug delivery system to prevent implant-associated infection in TJA surgery. [ABSTRACT FROM AUTHOR]

Abstract: Hydroxyapatite (HA)/chitosan nanohybrid coatings (HA/CS/CFs) on porous carbon fiber felts (PCFFs) have been fabricated according to the following stages: (i) deposition of chitosan/calcium phasphate precursors on PCFFs by dip-coating method and (ii) in situ formation of HA/CS/CFs by biomimetic method. PCFFs are covered uniformly with HA nanorods and chitosan, and the macropores in PCFFs still remained. Interestingly, the calcium-deficient HA nanorods with a diameter of ~20nm and length of 50–100nm possess poor crystallinity. HA/CS/CFs exhibit the excellent in vitro biocompatibility, which can improve adhesion, spreading, and proliferation of human bone marrow stromal cells (hBMSCs). Hence, HA/CS/CFs have great potential for bone scaffold materials. [Copyright &y& Elsevier]

Abstract: A multifunctional magnetic mesoporous bioactive glass (MMBG) has been widely used for a drug delivery system, but its biological properties have been rarely reported. Herein, the effects of mesopores and Fe3O4 nanoparticles on drug loading–release property, bactericidal property and biocompatibility have been investigated by using mesoporous bioactive glass (MBG) and non-mesoporous bioactive glass (NBG) as control samples. Both MMBG and MBG have better drug loading efficiency than NBG because they possess ordered mesoporous channels, big specific surface areas and high pore volumes. As compared with MBG, the Fe3O4 nanoparticles in MMBG not only provide magnetic property, but also improve sustained drug release property. For gentamicin-loaded MMBG (Gent-MMBG), the sustained release of gentamicin and the Fe3O4 nanoparticles minimize bacterial adhesion significantly and prevent biofilm formation against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Moreover, the magnetic Fe3O4 nanoparticles in MMBG can promote crucial cell functions such as cell adhesion, spreading and proliferation. The excellent biocompatibility and drug delivery property of MMBG suggest that Gent-MMBG has great potentials for treatment of implant-associated infections. [Copyright &y& Elsevier]

Abstract: Chitosan/carbonated hydroxyapatite composite coatings (CCHCs) were fabricated according to the following steps: (i) preparation of calcium carbonate coatings (CCCs) on Ti6Al4V substrates by electrophoretic deposition; (ii) transformation of CCCs into carbonated hydroxyapatite coatings (CHACs) in a phosphate buffer solution (PBS); and (iii) formation of CCHCs by modification of CHACs with chitosan. Inorganic constituents in CCHCs are plate-like carbonated hydroxyapatite particles with a low crystallinity. Interestingly, macropores with a pore size of 0.5–2μm still remain among the carbonated hydroxyapatite plates even after the chitosan deposits homogeneously on the coatings. Moreover, CCHCs have moderately hydrophilic surfaces with a contact angle of 29.4° due to the presence of the chitosan. Biocompatibility tests have been carried out by using human bone mesenchymal stem cells (hBMSCs) as cell models. The hBMSCs show better cell morphology, adhesion, spreading and proliferation on CCHCs than on CHACs. The excellent biocompatibility of CCHCs is mainly attributed to the organic/inorganic compositions, macroporous structure and moderately hydrophilic surfaces. Hence, CCHCs have great potentials for bone implants. [Copyright &y& Elsevier]

Abstract: Implant-associated infection is a serious problem in orthopaedic surgery. One of the most effective ways is to introduce a controlled antibiotics delivery system into the bone filling materials, achieving sustained release of antibiotics in the local sites of bone defects. In the present work, mesoporous carbonated hydroxyapatite microspheres (MCHMs) loaded with gentamicin have been fabricated according to the following stages: (i) the preparation of the MCHMs by hydrothermal method using calcium carbonate microspheres as sacrificial templates, and (ii) loading gentamicin into the MCHMs. The MCHMs exhibit the 3D hierarchical nanostructures constructed by nanoplates as building blocks with mesopores and macropores, which make them have the higher drug loading efficiency of 70–75% than the conventional hydroxyapatite particles (HAPs) of 20–25%. The gentamicin-loaded MCHMs display the sustained drug release property, and the controlled release of gentamicin can minimize significantly bacterial adhesion and prevent biofilm formation against S. epidermidis. The biocompatibility tests by using human bone marrow stromal cells (hBMSCs) as cell models indicate that the gentamicin-loaded MCHMs have as excellent biocompatibility as the HAPs, and the dose of the released gentamicin from the MCHMs has no toxic effects on the hBMSCs. Hence, the gentamicin-loaded MCHMs can be served as a simple, non-toxic and controlled drug delivery system to treat bone infections. [Copyright &y& Elsevier]

Chitosan (CTS) and mesoporous calcium silicate (MCS) have been developed for bone defect healing; however, their bone regeneration capacity still does not satisfy the patients with bone diseases. Gadolinium (Gd) is accumulated in human bones, and plays a beneficial role in regulating cell performance and bone regeneration. We firstly constructed Gd-doped MCS/CTS (Gd-MCS/CTS) scaffolds by a lyophilization technology. The interconnected arrangement of CTS films lead to forming macropores by using ice crystals as templates during the lyophilization procedure, and the Gd-MCS nanoparticles dispersed uniformly on the macropore walls. The biocompatible chemical components and hierarchical pores facilitated the attachment and spreading of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Interestingly, the Gd dopants in the scaffolds effectively activated the Wnt/β-catenin signaling pathway, resulting in excellent cell proliferation and osteogenic differentiation capacities. The osteogenic-related genes such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and collagen type1 (COL-1) were remarkably up-regulated by Gd-MCS scaffolds as compared with MCS scaffolds, and their expression levels increased in a positive correlation with Gd doping amounts. Moreover, in vivo rat cranial defect tests further confirmed that Gd-MCS/CTS scaffolds significantly stimulated collagen deposition and new bone formation. The exciting finding suggested the beneficial effects of Gd3+ ions on osteogenic differentiation and new bone regeneration, and Gd-MCS/CTS scaffolds can be employed as a novel platform for bone defect healing. Unlabelled Image • Gd-doped calcium silicate/chitosan scaffolds were developed for bone defect healing. • Interconnected arrangement of chitosan films induced macropore formation. • Gd dopants in porous scaffolds activated Wnt/β-catenin signaling pathway. • Gd-doped calcium silicate/chitosan scaffolds enhanced new bone regeneration. [ABSTRACT FROM AUTHOR]