Potential role of calcium sulfate/ß-tricalcium phosphate/graphene oxide nanocomposite for bone graft application_mechanical and biological analyses.

BACKGROUND: Bone grafts are extensively used for repairing bone defects and voids in orthopedics and dentistry. Moldable bone grafts offer a promising solution for treating irregular bone defects, which are often difficult to fill with traditional rigid grafts. However, practical applications have been limited by insufficient mechanical strength and rapid degradation. METHODS: This study developed a ceramic composite bone graft composed of calcium sulfate (CS), ß-tricalcium phosphate (ß-TCP) with/without graphene oxide (GO) nano-particles. The biomechanical properties, degradation rate, and in-vitro cellular responses were investigated. In addition, the graft was implanted in-vivo in a critical-sized calvarial defect model. RESULTS: The results showed that the compressive strength significantly improved by 135% and the degradation rate slowed by 25.5% in comparison to the control model. The addition of GO nanoparticles also improved cell compatibility and promoted osteogenic differentiation in the in-vitro cell culture study and was found to be effective at promoting bone repair in the in-vivo animal model. CONCLUSIONS: The mixed ceramic composites presented in this study can be considered as a promising alternative for bone graft applications.

Effects of online high-definition transcranial direct current stimulation over left dorsolateral prefrontal cortex on predominant negative symptoms and EEG functional connectivity in patients with schizophrenia: a randomized, double-blind, controlled trial.

AIMS: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design. METHODS: Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity. RESULTS: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network. CONCLUSIONS: High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting.

Zigzag Barbed Polydioxanone Thread Implantation and Evaluation Using Polydimethylsiloxane Model to Simulate Thread Migration in Tissue.

Facial lifting with polydioxanone barbed threads has been widely used in aesthetic treatment for years. However, gravity resists the thread and continuously pulls the face downward. This study aims to determine methods to lift the skin more efficiently with longer longevity. The quality of the thread is important and is defined by the pulling and pullout strengths. Moreover, the method of using threads is also important. We compared five thread-implantation techniques and six angles for the V-shaped implantation methods using a polydimethylsiloxane model to simulate thread migration in tissues. The results of the simulated thread-lift techniques can provide valuable information for physicians, enabling a more precise design of facelift surgery techniques.

The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models.

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges.

Enhanced Vascular-like Network Formation of Encapsulated HUVECs and ADSCs Coculture in Growth Factors Conjugated GelMA Hydrogels.

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.

Improving the Physical Properties of Starch-Based Powders for Potential Anti-Adhesion Applications.

Postoperative adhesion is one of the most common complications that occur during and after surgery; thus, materials that can prevent adhesion are often applied. Starch powders with a high water absorption capacity are preferred, and many studies have focused on increasing the water absorption of modified starches, as native starch powders display poor water-holding capacities. The effects of salts on the physical properties of acetylated distarch phosphate potato starch powders were investigated here. Changes in functional groups, the crystal structures of modified starch, particle morphologies, water absorption, viscosity, and in vivo adhesion were investigated. The results showed that salts greatly improved the water absorption and viscosity of acetylated distarch phosphate potato starch powders. Among the three different salt-modified starch powders, NaCl-modified starch powders displayed higher water absorption and viscosity and demonstrated better in vivo anti-adhesion performance. The results of this study propose a potential biomaterial that may function as an anti-adhesive, potentially leading to reduced surgical risks and a better quality of life for patients.

Survival of Four Conical Implant Abutment Connections After Removal of the Abutment Screw and Simulated Cyclic Loading: An In Vitro Comparative Study.

This in vitro study evaluated the mechanical behavior of different conical connection implant systems after abutment screw withdrawal. Four conical connection systems were selected based on different conical half-angles: Ankylos (5.7°), Cowell (7.0°), Straumann (7.5°), and Astra (11.0°). In each system, 5 implants and abutments were used (n = 5). According to the recommended value, each abutment screw was torqued to settle the abutment and then withdrawn through a predesigned hole of the cemented crown. The retentiveness of the abutment was evaluated by the following mechanical testing. All specimens were subjected to cyclic loading of 20-200 N, 30°, and 4-mm off-axis to the implant axis, for 106 cycles. The pullout forces and axial displacements of the abutments were measured. The data of the Cowell system was obtained from our previous work. All groups other than Astra group, in which abutment loosened after abutment screw withdrawal, passed the cyclic loading test. Straumann group demonstrated a significantly lower pullout force (27.4 ± 21.1 N) than Ankylos (160.1 ± 41.4 N) and Cowell (183.7 ± 30.5 N) groups. All groups showed abutment rebound after screw withdrawal except Straumann group. In addition, Ankylos, Cowell, and Straumann groups demonstrated axial displacement after cyclic loading. In terms of the retentiveness of the abutment after abutment screw withdrawal examined in this study, Ankylos and Cowell groups had much higher retentiveness than Straumann group, while Astra group had none. Conical angle could be a key design parameter to make abutment screw withdrawal after conical abutment settlement feasible, but more studies must be conducted for clinical application.

Effects of Chitosan on Chondrocytes Derived from Human Nasal Septal Cartilage.

BACKGROUND/AIM: The aim of this study was to evaluate the influence of chitosan on the growth of nasal septal chondrocytes (NSCs). The final goal was to establish a novel methodology to enhance nasal septal cartilage regeneration. MATERIALS AND METHODS: Human NSCs were isolated and their morphology was examined using Alcian blue staining and observed by light microscopy. The isolated NSCs were grown with various concentrations of chitosan and the expression of COL2A1 was investigated. RESULTS: NSCs were successfully isolated from nasal septal cartilage. Co-culture with 0.2% of chitosan greatly enhanced proliferation of NSCs compared to control cells. However, 0.5% of chitosan was harmful to NSCs, resulting in cell detachment from the culture plate. Furthermore, the addition of 0.2% chitosan significantly improved the expression of COL2A1 in NSCs. CONCLUSION: To our knowledge, this is the first report to demonstrate that chitosan could effectively guide the attachment and growth of human NSCs. Chitosan appears to be a promising additive for NSC culture, which sets the stage for studying tissue regeneration in nasal septal cartilage deficiency, rhinoplasty, and craniofacial reconstruction.

Lidocaine induces epithelial­mesenchymal transition and aggravates cancer behaviors in non­small cell lung cancer A549 cells.

The effects of clinically relevant concentrations of lidocaine on epithelial-mesenchymal transition (EMT) and associated lung cancer behaviors have rarely been investigated. The aim of the present study was to assess the impact of lidocaine on EMT and its related phenomena, including chemoresistance. Lung cancer cell lines (A549 and LLC.LG) were incubated with various concentrations of lidocaine, 5-fluorouracil (5-FU) or both to test their effects on cell viability. Subsequently, the effects of lidocaine on various cell behaviors were assessed in vitro and in vivo using Transwell migration, colony-formation and anoikis-resistant cell aggregation assays, and human tumor cell metastasis in a chorioallantoic membrane (CAM) model quantitated by PCR analysis. Prototypical EMT markers and their molecular switch were analyzed using western blotting. In addition, a conditioned metastasis pathway was generated through Ingenuity Pathway Analysis. Based on these measured proteins (slug, vimentin and E-cadherin), the molecules involved and the alteration of genes associated with metastasis were predicted. Of note, clinically relevant concentrations of lidocaine did not affect lung cancer cell viability or alter the effects of 5-FU on cell survival; however, at this dose range, lidocaine attenuated the 5-FU-induced inhibitory effect on cell migration and promoted EMT. The expression levels of vimentin and Slug were upregulated, whereas the expression of E-cadherin was downregulated. EMT-associated anoikis resistance was also induced by lidocaine administration. In addition, portions of the lower CAM with a dense distribution of blood vessels exhibited markedly increased Alu expression 24 h following the inoculation of lidocaine-treated A549 cells on the upper CAM. Thus, at clinically relevant concentrations, lidocaine has the potential to aggravate cancer behaviors in non-small cell lung cancer cells. The phenomena accompanying lidocaine-aggravated migration and metastasis included altered prototypical EMT markers, anoikis-resistant cell aggregation and attenuation of the 5-FU-induced inhibitory effect on cell migration.

In vitro studies of factors affecting debridement of dental implants by tricalcium phosphate powder abrasive treatment.

Peri-implantitis is a common complication characterized by inflammation in tissues surrounding dental implants due to plaque accumulation, which can lead to implant failure. While air flow abrasive treatment has been found to be effective for debriding implant surfaces, little is known about the factors that affect its cleaning capacity. This study systematically examined the cleaning capacity of air powder abrasive (APA) treatment with ß-tricalcium phosphate (ß-TCP) powder, using various powder jetting strengths and different particle sizes. Three sizes of ß-TCP powder (S, M, and L) were prepared, and different powder settings (low, medium, and high) were tested. The cleaning capacity was determined by quantifying ink removal, which simulated biofilm removal from the implant surfaces at different time points. The results of the systematic comparisons showed that the most efficient cleaning of implant surfaces was achieved using size M particles with medium setting. Additionally, the amount of powder consumed was found to be critical to cleaning efficiency, and the implant surfaces were altered in all tested groups. These systematically analyzed outcomes may provide insights into the development of potential non-surgical strategies for treating peri-implant diseases.

Long-term effects of tear film component deposition on the surface and optical properties of two different orthokeratology lenses.

PURPOSE: To understand the effects of long-term deposition of tear film components on the surface and optical properties of orthokeratology (ortho-k) lenses, two different lenses, Brighten 22 and Optimum Extra, were tested here. METHODS: Ortho-k lenses were immersed in artificial tears and cleaned with a commercial care solution repeatedly for up to 90 days. Both the daily and accumulated lysozyme deposition amounts using an Enzyme-Linked ImmunoSorbent Assay were then analyzed. The base curve, central thickness, power, and transmission of visible light, ultraviolet A, and ultraviolet B were analyzed before and after repeated tear film component deposition procedures. The surface roughness using atomic force microscopy was observed and an energy dispersive spectrometer was used to analyze the composition of the deposits. RESULTS: The highest levels of lysozyme were adsorbed on both lens materials during the first four days of the procedure and became saturated by day 6. For both lens materials, contamination on the lenses was easily observed by day 30, and the degree of surface roughness was higher. The transmission levels of different light spectrums were reduced showing that the optical characteristics of both lenses were also affected. CONCLUSIONS: The results provide in vitro evidence that lysozyme could not be completely removed from orthokeratology lenses. Both surface and optical properties were affected by the deposition of tear film components. However, only one commercial multipurpose care solution was used to clean the lens in this study when the main ingredient was a surfactant, and the results might be different when other care regimens with other key ingredients are used. In addition, whether tear film component deposition might result in increased risks of infection or corneal abrasion will require further investigation.

Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment.

Background: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis. Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery. Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV's cornea. Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.

Unusual capitate fracture with dorsal shearing pattern and concomitant carpometacarpal dislocation with a 6-year follow-up: A case report.

BACKGROUND: Isolated capitate fractures are rare carpal fractures. Following high-energy injuries, capitate fractures are usually associated with other carpal fractures or ligament injuries. The management of capitate fractures depends on the fracture pattern. Here, we report an unusual capitate fracture with a dorsal shearing pattern and concomitant carpometacarpal dislocation, with a 6-year follow-up. To the best of our knowledge, this fracture pattern and surgical management have not been previously reported. CASE SUMMARY: A 28-year-old man presented with left-hand volar tenderness and decreased grip strength that persisted for one month after a traffic accident. Radiography showed a distal capitate fracture with carpometacarpal joint incongruence. Computed tomography (CT) revealed a distal capitate fracture with carpometacarpal joint dislocation. The distal fragment was rotated by 90° in the sagittal plane, and an oblique shearing fracture pattern was noted. Open reduction and internal fixation (ORIF) with a locking plate were performed using the dorsal approach. The imaging studies performed 3 mo and 6 years following surgery revealed a healed fracture, and the Disabilities of the Arm, Shoulder, and Hand and visual analog scale scores were significantly improved. CONCLUSION: CT can detect capitate fractures with dorsal shearing pattern and concomitant carpometacarpal dislocation. ORIF using a locking plate are possible.

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines.

BACKGROUND/AIM: Surface biomarkers, such as CD44 and CD133, have been demonstrated to be expressed in prostate cancer cells, and our previous study has shown that prostate cancer cell lines could be divided into three groups according to the single and combined expression pattern of CD44 and 133. In order to refine prognostication in prostate cancer cells, we further investigated genetic biomarkers, prostate cancer antigen 3 (PCA3), kallikrein 4 (KLK4), and KLK9 in different prostate cancer cell lines. MATERIALS AND METHODS: CWR22Rv1, PC3, and DU145 cell lines were cultured until 95% confluence. The single expression of CD44 or CD133 and their combined expression were analyzed by flow cytometry, and gene expression of b-actin, PCA3, KLK4, and KLK9 was analyzed by real-time polymerase chain reaction. RESULTS: The single expression of CD133 was less than 4% in all cell lines examined. PC3 and DU145 cells displayed a high expression of CD44 (>91%), whereas CWR22Rv1 was the only cell line that demonstrated a high co-expression of both CD44 and CD133 (>91%). In addition, PC3 and DU145 displayed low expression of PCA3, KLK4, and KLK9 when compared with their own b-actin expression. In contrast, CWR22Rva showed high expression of PCA3 and KLK4 although KLK9 expression was also low. CONCLUSION: Both surface and genetic biomarkers should be validated for a more accurate prognosis in prostate cancer.

Investigation and Characterization of Factors Affecting Rheological Properties of Poloxamer-Based Thermo-Sensitive Hydrogel.

Poloxamers are negatively temperature-sensitive hydrogels and their hydrophilic groups interact with water molecules at lower temperatures (liquid phase) while their hydrophobic groups interact more strongly with increases in temperature causing gelation. To investigate the factors affecting the rheological properties of poloxamers, various parameters including different poloxamer P407 concentrations, poloxamers P407/P188 blending ratios and additives were examined. The results presented a clear trend of decreasing gelling temperature/time when P407 was at higher concentrations. Moreover, the addition of P188 enhanced the gelling temperature regardless of poloxamer concentration. Polysaccharides and their derivatives have been widely used as components of hydrogel and we found that alginic acid (AA) or carboxymethyl cellulose (CMC) reduced the gelling temperature of poloxamers. In addition, AA-containing poloxamer promoted cell proliferation and both AA -and CMC-containing poloxamer hydrogels reduced cell migration. This study investigated the intriguing characteristics of poloxamer-based hydrogel, providing useful information to compounding an ideal and desired thermo-sensitive hydrogel for further potential clinical applications such as development of sprayable anti-adhesive barrier, wound-healing dressings or injectable drug-delivery system for cartilage repair.

Preparation and Characterization of Extracellular Matrix Hydrogels Derived from Acellular Cartilage Tissue.

Decellularized matrices can effectively reduce severe immune rejection with their cells and eliminated nucleic acid material and provide specific environments for tissue repair or tissue regeneration. In this study, we prepared acellular cartilage matrix (ACM) powder through the decellularization method and developed ACM hydrogels by physical, chemical, and enzymatic digestion methods. The results demonstrated that the small size group of ACM hydrogels exhibited better gel conditions when the concentration of ACM hydrogels was 30 and 20 mg/mL in 1N HCl through parameter adjustment. The data also confirmed that the ACM hydrogels retained the main components of cartilage: 61.18% of glycosaminoglycan (GAG) and 78.29% of collagen, with 99.61% of its DNA removed compared to samples without the decellularization procedure (set as 100%). Through turbidimetric gelation kinetics, hydrogel rheological property analysis, and hydrogel tissue physical property testing, this study also revealed that increasing hydrogel concentration is helpful for gelation. Besides, the ex vivo test confirmed that a higher concentration of ACM hydrogels had good adhesive properties and could fill in cartilage defects adequately. This study offers useful information for developing and manufacturing ACM hydrogels to serve as potential alternative scaffolds for future cartilage defect treatment.

Thermosensitive hydrogel carrying extracellular vesicles from adipose-derived stem cells promotes peripheral nerve regeneration after microsurgical repair.

Peripheral nerve injuries are commonly occurring traumas of the extremities; functional recovery is hindered by slow nerve regeneration (<1 mm/day) following microsurgical repair and subsequent muscle atrophy. Functional recovery after peripheral nerve repair is highly dependent on local Schwann cell activity and axon regeneration speed. Herein, to promote nerve regeneration, paracrine signals of adipose-derived stem cells were applied in the form of extracellular vesicles (EVs) loaded in a thermosensitive hydrogel (PALDE) that could solidify rapidly and sustain high EV concentration around a repaired nerve during surgery. Cell experiments revealed that PALDE hydrogel markedly promotes Schwann-cell migration and proliferation and axon outgrowth. In a rat sciatic nerve repair model, the PALDE hydrogel increased repaired-nerve conduction efficacy; contraction force of leg muscles innervated by the repaired nerve also recovered. Electromicroscopic examination of downstream nerves indicated that fascicle diameter and myeline thickness in the PALDE group (1.91 ± 0.61 and 1.06 ± 0.40 µm, respectively) were significantly higher than those in PALD and control groups. Thus, this EV-loaded thermosensitive hydrogel is a potential cell-free therapeutic modality to improve peripheral-nerve regeneration, offering sustained and focused EV release around the nerve-injury site to overcome rapid clearance and maintain EV bioactivity in vivo.

The Effect of Polysaccharides on Preventing Proteins and Cholesterol from Being Adsorbed on the Surface of Orthokeratology Lenses.

The adsorption of tear film compositions such as proteins and lipids on the orthokeratology lenses often lead to infection or corneal damage. In order to investigate whether polysaccharides could prevent tear compositions from being adsorbed on the lens, alginic acid and lambda-carrageenan were added into artificial tear solution. By measuring daily adsorption of cholesterol, lysozyme, and albumin, our results showed that polysaccharides could weakly prevent cholesterol adsorption. In addition, polysaccharides could also reduce albumin deposition over time. Although the effect of polysaccharides on lysozyme adsorption was distinct depending on the concentrations of polysaccharides, the overall results demonstrated that polysaccharides could decrease protein deposition over time. Our results provided an in vitro evidence that polysaccharides may be applied as coating materials on the lens or as the composition of artificial tear solutions or eyedrops, in order to prevent adsorption of tear film compositions that may lead to a reduced incidence of infection or corneal damage for orthokeratology lens wearers.

The efficacy of vancomycin-loaded biphasic calcium phosphate bone substitute in the promotion of new bone growth and the prevention of postoperative infection.

Background: Due to the increasing need for suitable alternatives to bone grafts, artificial bones made of biphasic calcium phosphate (BCP) are currently being extensively researched. These porous bone substitutes have also demonstrated considerable incorporation with the host bone, and new bone is able to grow within the porous structure. They therefore offer a potential therapeutic approach for bone defects. Methods: Vancomycin-loaded Bicera™, a BCP bone substitute, was investigated in order to prevent implant-associated osteomyelitis and postoperative infection after orthopedic surgery. The loading capacity of Bicera™ was measured to understand its potential antibiotic adsorption volume. An antibiotic susceptibility test was also carried out to analyze the effect of Bicera™ loaded with different concentrations of vancomycin on the growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin-loaded Bicera™ was implanted into rabbits with bone defects, and general gross, radiographic, and histological evaluation was undertaken at 4, 12, and 24 weeks after implantation. Results: The maximum loading capacity of vancomycin-loaded Bicera™ was 0.9 ml of liquid regardless of the vancomycin concentration. Antibiotic susceptibility tests showed that vancomycin-loaded Bicera™ inhibited the growth of MRSA for 6 weeks. In addition, animal studies revealed that new bone grew into the vancomycin-loaded Bicera™. The percentage of new bone formation from 4 to 24 weeks after implantation increased from 17% to 36%. Conclusion: Vancomycin-loaded Bicera™ could effectively inhibit the growth of MRSA in vitro. It was found to incorporate into the host bone well, and new bone was able to grow within the bone substitute. The results of this study indicate that vancomycin-loaded Bicera™ is a potential bone substitute that can prevent implant-associated osteomyelitis and postoperative infection.

Development of Injectable Calcium Sulfate and Self-Setting Calcium Phosphate Composite Bone Graft Materials for Minimally Invasive Surgery.

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty.