Osteocytes Influence on Bone Matrix Integrity Affects Biomechanical Competence at Bone-Implant Interface of Bioactive-Coated Titanium Implants in Rat Tibiae

Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.

Factors Associated with Bone Erosion in Patients with Gout: A Dual-Energy Gemstone Spectral Imaging Computed Tomography Study

ABSTRACT Objective This study aimed to assess the factors influencing bone erosion in patients with gout using dual-energy gemstone spectral imaging CT. Methods We compared the clinical data, laboratory indices, and tissue urate levels at the monosodium urate (MSU)-bone interface measured by dual-energy gemstone spectral imaging computed tomography of 87 gout patients with (n=41) and without (n=46) bone erosion. Logistic regression analysis was used to investigate the risk factors associated with bone erosion. Results In total, 47.1% of patients with gout had bone erosion. The disease duration, serum uric acid, tissue urate levels, and the presence of tophi were significantly higher (p<0.05) in gout patients with bone erosion than in those without bone erosion. Longer disease duration (OR=1.11, 95% CI: 1.00–1.24, p<0.05) and increased tissue urate levels (OR=1.01, 95% CI: 1.00–1.02, p<0.05) were independently associated with bone erosion. Tissue urate levels at the MSU-bone interface were correlated with the presence of tophi (r=0.62, p<0.001), bone erosion (r=0.51, p<0.001), renal calculus (r=0.24, p=0.03), and serum uric acid levels (r=0.23, p=0.03). Conclusion This study found that longer disease duration and elevated tissue urate concentrations at the MSU-bone interface were associated with bone erosion in patients with gout.

Nanog/NFATc1/Osterix signaling pathway-mediated promotion of bone formation at the tendon–bone interface after ACL reconstruction with De-BMSCs transplantation

Background Bone formation plays an important role in early tendon–bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon–bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Methods BMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon–bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Results De-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon–bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN. Conclusions De-BMSCs transplantation could promote bone formation at the tendon–bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.

A Dual-Factor Releasing Hydrogel for Rotator Cuff Injury Repair

Rotator cuff injury causes pain in the shoulder and is a challenge to be repaired even after surgical reconstruction. Here, we developed a dual-factor releasing hydrogel based on sulfhydrylated chitosan to deliver KGN and FGF-2 to the injured area to enable fast healing of the tendon–bone interface, which is essential for the repair of rotator cuff injury. We found that the two factors could be easily loaded into the hydrogel, which could in turn continuously release the factors in physiological conditions. The hydrogel was found to be a porous structure through a scanning electron microscope (SEM). The micropores in the hydrogel structure enable the loading and releasing of these molecules. This study showed that KGN and FGF-2 could play a synergistic effect by recruiting and promoting stem cell proliferation and chondrogenesis, thus accelerating the healing of the tendon–bone interface. An in vivo study based on a rabbit rotator cuff injury model demonstrated that the dual-factor releasing hydrogel possesses superior repair capacity than a single-factor releasing hydrogel and the untreated groups. In conclusion, the KGN and FGF-2 dual-factor releasing hydrogel could be a promising biomaterial for the regeneration of the tendon–bone interface and rotator cuff injury repair.

Stress Distribution Along the Implant-Bone Interface: A Pilot Study using Finite Element Analysis to Compare Tilted and Non-Tilted Implants under Different Loads

Introduction: This study used finite element analysis to evaluate stress distribution of implants placed at different angulations under two loadings. Stress was measured at the implant-bone interface. Methods: Four models of implant and bone were manufactured via three-dimensional optical scanning and point cloud data extraction. They included implants placed: 1) Without tilt 2) tilted at 15o, 3) tilted at 30o, and 4) tilted at 45o. A tissue-level implant was scanned, and a mandible bone model was extracted from cone-beam computed tomography systems. A 3D model of the implants in the mandible were constructed. The finite element analyses were carried out using simulation software. The physical interaction at implant-bone interfaces during loading were considered through bonded surface-to-surface contacts. Static loading (with axial forces of 150N and 300N) were applied to evaluate the implant-bone model. Results: The amount of stress along the implant-bone interface was greater under 300N loading than 150N loading. The stress along tilted implants were greater than that of non-tilted implants under both 150N and 300N. There was no significant variance among the various angles of implants. The displacements along the tilted implants were larger than those of nontilted implants. The stress distribution along the implant-bone interface increased when the loading increased. Conclusion: The tilted implants presented greater stress distribution. The in vitro stress distribution analysis using FEA will provide clinical guidance for implant placement.