3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Three-dimensional-printed MPBI@ß-TCP scaffold promotes bone regeneration and impedes osteosarcoma under near-infrared laser irradiation.

Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2 )/polydopamine (PDA)/-bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the ß-TCP scaffold and analyzed the outcomes. The MoS2 /PDA-BMP2-IGF-1@ß-TCP (MPBI@ß-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@ß-TCP scaffold was evaluated. It was found that MPBI@ß-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@ß-TCP. Additionally, MPBI@ß-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@ß-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@ß-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@ß-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.

Combined Effect of a Bioinspired Self-Assembling Peptide and Fluoride Varnish on Remineralisation of Artificial Early Enamel Caries Lesion: An in vitro Study.

INTRODUCTION: This study aimed to investigate the remineralisation effect of combined use of a bioinspired self-assembling peptide (P26) and fluoride varnish on artificial early enamel caries lesions. METHODS: Bovine enamel blocks with artificial early enamel caries lesions were prepared. The blocks were randomly allocated to four experimental groups to receive the following treatments: A = P26 + fluoride varnish, B = P26, C = fluoride varnish, and D. distilled water (negative control). The treated blocks were subjected to pH cycling. Enamel blocks were collected at time points of 7 days (d7) and 21 days (d21). The mineral gain, elemental analysis and crystal characteristics of the caries lesion were assessed by micro-computed tomography, scanning electron microscopy with energy dispersive X-ray and X-ray diffraction (XRD), respectively. RESULTS: The mean ± standard deviation of mineral gain of group A to D were 17.4 ± 4.2%, 10.7 ± 2.2%, 10.1 ± 1.2%, and 6.8 ± 0.5% at d7, respectively, and 15.2 ± 2.6%, 8.7 ± 3.1%, 9.7 ± 1.2%, and 7.8 ± 2.3% at d21, respectively. A significant higher mineral gain was observed in group A when compared to other groups at both d7 and d21 (p < 0.05). The calcium-to-phosphate ratio remained consistent across all groups, ranging between 1.2 and 1.4. XRD analysis indicated that crystal composition on the surfaces was apatite for all groups. CONCLUSION: In conclusion, the present study provided a first indication of better remineralisation effects of the combined use of the bioinspired self-assembling peptide P26 and fluoride varnish compared to the effects of the respective individual uses of P26 or fluoride varnish.

Improvement of absorbability, osteoconductivity, and strength of a ß-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.

BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new ß-tricalcium phosphate (ß-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional ß-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each ß-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

Optimization of Parameters for Atom Probe Tomography Analysis of ß-Tricalcium Phosphates.

The biocompatibility and resorption characteristics of ß-tricalcium phosphate (ß-TCP, Ca3(PO4)2) have made it a coveted alternative for bone grafts. However, the underlying mechanisms governing the biological interactions between ß-tricalcium phosphate and osteoclasts remain elusive. It has been speculated that the composition at grain boundaries might vary and affect ß-TCP resorption properties. Atom probe tomography (APT) offers a quantitative approach to assess the composition of the grain boundaries, and thus advance our comprehension of the biological responses within the microstructure and chemical composition at the nanoscale. The precise quantitative analysis of chemical composition remains a notable challenge in APT, primarily due to the influence of measurement conditions on compositional accuracy. In this study, we investigated the impact of laser pulse energy on the composition of ß-TCP using APT, aiming for the most precise Ca:P ratio and consistent results across multiple analyses performed with different sets of analysis conditions and on two different instruments.

Remineralization of post-orthodontic white spot lesions with a fluoride varnish and a self-assembling P 11 - 4 peptides: a prospective in-vivo-study.

OBJECTIVE: The objective was to evaluate the remineralization effects of fluoride varnish (Clinpro White varnish), self-assembling peptide (Curodont™ Repair) and their combined use on WSL after orthodontic treatment. MATERIALS AND METHODS: Thirty-two subjects, aged of 10-18 (mean age 13.91 ± 2.92) with 107 post-orthodontic WSL were included in the study. Subjects were divided into four groups as control, tricalcium phosphate (TCP) containing fluoride varnish (Clinpro White varnish) group, self-assembling P11-4 peptides (Curodont™ Repair) group and combined application of the two products. At the beginning, each subjects' caries risk profile was assessed by evaluating diet cariogenicity, plaque index, gingival bleeding index and stimulated salivary flow rate. Before the application of the remineralization agents, WSL baseline demineralization values were determined with QLF Inspektor™ Pro, laser fluorescence using DIAGNOdent and color values were measured by Vita EasyShade. Remineralization data were obtained by measuring ΔF, ΔQ, and lesion area with QLF. The aesthetic improvement after the remineralization process was evaluated with a spectrophotometer at six weeks, three and six months. RESULTS: No statistically significant differences were found between the groups in terms of criteria determining patients' caries risk profiles, DIAGNOdent data, and plaque index scores (p > 0.05). Intra-group evaluation following remineralization revealed statistically significant increases in ΔF and ΔQ with a decrease in lesion area for the fluoride varnish group at six months, for the peptide group at three months, and for the combined application group at three and six months (p < 0.05). In inter-group comparisons, ΔF and ΔQ values were found to be statistically significant only in the fluoride group at six months compared to the other groups (p < 0.05). While the L* value decreased significantly in all groups at six months, a statistically significant difference in ΔE* values was observed only in the control group between three and six months. CONCLUSION: Fluoride varnish with TCP showed highest remineralization at 6 months, and the remineralization was positively affected in the short term (three months) after the use of self-assembling P11-4 peptides and their combined application. CLINICAL RELEVANCE: Remineralization obtained after single application of agents tested in six months in-vivo showed parallel results. In an attempt to trigger subsurface remineralization, the combined use of fluoride with self-assembling peptides as biomimetic remineralization agent needs further evaluation.

3D-printed polycaprolactone scaffolds coated with beta tricalcium phosphate for bone regeneration.

BACKGROUND/PURPOSE: 3D-printing technology is an important tool for the bone tissue engineering (BTE). The aim of this study was to investigate the interaction of polycaprolactone (PCL) scaffolds and modified mesh PCL coated with beta TCP (PCL/ß-TCP) scaffolds with MG-63. METHODS: This study used the fused deposition modeling (FDM) technique with the 3D printing technique to fabricate the thermoplastic polymer and composite scaffolds. Scaffold structure and coating quality were observed under a scanning electron microscope (SEM). MG-63 cells were injected and attached to the mesh-manufactured PCL scaffolds. The biocompatibility of mesh structured PCL and PCL/ß-TCP scaffolds could be examined by measuring the viability of MG-63 cells of MTT assay. Bone cell differentiation was evaluated ALP activity by mineralization assay. RESULTS: The results showed that both mesh PCL scaffolds and PCL/ß-TCP scaffolds were non-toxic to the cells. The ALP activities of cells in PCL/ß-TCP scaffolds groups were significant differences and better than PCL groups in all groups at all experimental dates. The mineralization process was time-dependent, and significantly higher mineralization of osteosarcoma cells was observed on PCL/ß-TCP scaffolds at experimental dates. CONCLUSION: We concluded that both meshes structured PCL and PCL/ß-TCP scaffolds could promote the MG-63 cell growth, and PCL/ß-TCP was better than the PCL scaffolds for the outcome of MG63 cell differentiation and mineralization.

Functionalization of Ceramic Scaffolds with Exosomes from Bone Marrow Mesenchymal Stromal Cells for Bone Tissue Engineering.

The functionalization of bone substitutes with exosomes appears to be a promising technique to enhance bone tissue formation. This study investigates the potential of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) to improve bone healing and bone augmentation when incorporated into wide open-porous 3D-printed ceramic Gyroid scaffolds. We demonstrated the multipotent characteristics of BMSCs and characterized the extracted exosomes using nanoparticle tracking analysis and proteomic profiling. Through cell culture experimentation, we demonstrated that BMSC-derived exosomes possess the ability to attract cells and significantly facilitate their differentiation into the osteogenic lineage. Furthermore, we observed that scaffold architecture influences exosome release kinetics, with Gyroid scaffolds exhibiting slower release rates compared to Lattice scaffolds. Nevertheless, in vivo implantation did not show increased bone ingrowth in scaffolds loaded with exosomes, suggesting that the scaffold microarchitecture and material were already optimized for osteoconduction and bone augmentation. These findings highlight the lack of understanding about the optimal delivery of exosomes for osteoconduction and bone augmentation by advanced ceramic scaffolds.

Characterization of Porous ß-Type Tricalcium Phosphate Ceramics Formed via Physical Foaming with Freeze-Drying.

Porous ß-tricalcium phosphate (Ca3(PO4)2; ß-TCP) was prepared via freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing ß-TCP slurries above a liquid nitrogen surface at -180 °C with subsequent immersion in liquid nitrogen at -196 °C. These materials were then dried under reduced pressure in a freeze-dryer, after which they were sintered with heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the ß-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of 1.24 ± 0.25 µm and macroscopic, interconnected pores of 25.8 ± 4.7 µm in size. The effects of nonionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity, whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (>75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Three-Dimensionally Cultured Jaw Periosteal Cells Attenuate Macrophage Activation of CD4+ T Cells and Inhibit Osteoclastogenesis.

The implementation of a successful therapeutic approach that includes tissue-engineered grafts requires detailed analyses of graft-immune cell interactions in order to predict possible immune reactions after implantation. The phenotypic plasticity of macrophages plays a central role in immune cell chemotaxis, inflammatory regulation and bone regeneration. The present study addresses effects emanating from JPC-seeded ß-TCP constructs (3DJPCs) co-cultivated with THP-1 derived M1/M2 macrophages within a horizontal co-culture system. After five days of co-culture, macrophage phenotype and chemokine secretion were analyzed by flow cytometry, quantitative PCR and proteome arrays. The results showed that pro-inflammatory factors in M1 macrophages were inhibited by 3DJPCs, while anti-inflammatory factors were activated, possibly affected by the multiple chemokines secreted by 3D-cultured JPCs. In addition, osteoclast markers of polarized macrophages were inhibited by osteogenically induced 3DJPCs. Functional assays revealed a significantly lower percentage of proliferating CD4+ T cells in the groups treated with secretomes from M1/M2 macrophages previously co-cultured with 3DJPCs compared to controls without secretomes. Quantifications of pit area resorption assays showed evidence that supernatants from 3DJPCs co-cultured with M1/M2 macrophages were able to completely suppress osteoclast maturation, compared to the control group without secretomes. These findings demonstrate the ability of 3D cultured JPCs to modulate macrophage plasticity.

Performance of microbial inoculation and tricalcium phosphate on nitrogen retention and conversion: Core microorganisms and enzyme activity during kitchen waste composting.

The substantial release of NH3 during composting leads to nitrogen (N) losses and poses environmental hazards. Additives can mitigate nitrogen loss by adsorbing NH3/NH4, adjusting pH, and enhancing nitrification, thereby improving compost quality. Herein, we assessed the effects of combining bacterial inoculants (BI) (1.5%) with tricalcium phosphate (CA) (2.5%) on N retention, organic N conversion, bacterial biomass, functional genes, network patterns, and enzyme activity during kitchen waste (KW) composting. Results revealed that adding of 1.5%/2.5% (BI + CA) significantly (p < 0.05) improved ecological parameters, including pH (7.82), electrical conductivity (3.49 mS/cm), and N retention during composting. The bacterial network properties of CA (265 node) and BI + CA (341 node) exhibited a substantial niche overlap compared to CK (210 node). Additionally, treatments increased organic N and total N (TN) content while reducing NH4+-N by 65.42% (CA) and 77.56% (BI + CA) compared to the control (33%). The treatments, particularly BI + CA, significantly (p < 0.05) increased amino acid N, hydrolyzable unknown N (HUN), and amide N, while amino sugar N decreased due to bacterial consumption. Network analysis revealed that the combination expanded the core bacterial nodes and edges involved in organic N transformation. Key genes facilitating nitrogen mediation included nitrate reductase (nasC and nirA), nitrogenase (nifK and nifD), and hydroxylamine oxidase (hao). The structural equation model suggested that combined application (CA) and microbial inoculants enhance enzyme activity and bacterial interactions during composting, thereby improving nitrogen conversion and increasing the nutrient content of compost products.

Long-Term Outcomes and a Radiological Assessment of Hydroxyapatite-Tricalcium Phosphate-Coated Total Hip Arthroplasty (Trilogy/Zimmer): A Long-Term Follow-Up Study.

Background and Objectives: Favorable short- and mid-term results for hydroxyapatite (HA)-tricalcium phosphate (TCP)-coated total hip arthroplasty (THA) (Trilogy/Zimmer) have been reported in the literature; however, the long-term results beyond 15 years have not been documented. Therefore, this study evaluated the long-term postoperative results, radiological bone changes, and implant fixation of the acetabular component of HA-TCP-coated THA. Materials and Methods: This is a retrospective cohort study of 212 patients who underwent primary HA-TCP-coated THA (Trilogy/Zimmer) at our institution between 1 October 2002, and 31 March 2008; 166 who were available for follow-up at least 15 years postoperatively were included (capture rate: 78.3%). All implants were Trilogy/Zimmer. We investigated the survival rate, with aseptic loosening as the endpoint. Clinical evaluations included the presence of dislocation and a modified Harris Hip Score (mHHS) preoperatively and at the final observation. Results: The mean age at surgery and at the follow-up period were 57.7 ± 9.6 and 17.1 ± 1.5 years, respectively. The survival rate was 99.4% (165/166), with aseptic loosening as the endpoint. Dislocation was observed in 4/166 (2.4%) patients. The mHHS improved significantly from 46.1 points preoperatively to 82.2 points during the last survey (p < 0.05). The results revealed that fixation was favorable in all cases except for one case of aseptic loosening. The Trilogy implant coated with HA-TCP was highly effective in bone induction, and bone ingrowth was considered to have occurred without failure, further indicating its usefulness. The long-term results of cementless THA using an HA-TCP coating (Trilogy/Zimmer), with a mean follow-up period of 17.1 years, revealed a commendable survival rate of 99.4%, considering aseptic loosening as the endpoint. Conclusions: HA-TCP-coated THA (Trilogy/Zimmer) had good long-term results. However, further long-term observation is required in patients who have undergone this surgery, and the stem side should be evaluated and investigated, including comorbidities.

Stability of guided bone regeneration with two ratios of biphasic calcium phosphate at implant sites in the esthetic zone: A randomized controlled clinical trial.

AIMS: The aim of this randomized, double-blind, clinical trial was to compare the stability of the horizontal dimensions (facial bone thickness) of augmented bone using biphasic calcium phosphate (BCP) with hydroxyapatite/ß-tricalcium phosphate ratio of either 60/40 or 70/30. MATERIALS AND METHODS: Sixty dental implants placed with contour augmentation in the esthetic zone were randomized to 60/40 BCP (n = 30) or 70/30 BCP (n = 30). Cone-beam computed tomographic was used to assess facial bone thickness post-implantation and 6 months later at implant platform and 2, 4, and 6 mm apical to it. RESULTS: The percentage of horizontal dimension reduction was 23.64%, 12.83%, 9.62%, and 8.21% in 70/30 BCP group, while 44.26%, 31.91%, 25.88%, and 21.49% in 60/40 BCP group at the level of the implant platform and 2, 4, and 6 mm apical, respectively. Statistically significant difference was found at 6 months at all levels of measurement (p-value < .05). CONCLUSIONS: BCP bone grafts with HA/ß-TCP ratio of 60/40 and 70/30 showed comparable outcomes for contour augmentation simultaneously with implant placement. Interestingly, the 70/30 ratio was significantly superior in maintaining facial thickness and showed more stable horizontal dimensions of the augmented site.

Regeneration of critical-sized grade II furcation using a novel injectable melatonin-loaded scaffold.

BACKGROUND: Periodontal regenerative therapy using bone-substituting materials has gained favorable clinical significance in enhancing osseous regeneration. These materials should be biocompatible, osteogenic, malleable, and biodegradable. This study assessed the periodontal regenerative capacity of a novel biodegradable bioactive hydrogel template of organic-inorganic composite loaded with melatonin. MATERIALS AND METHODS: A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis. RESULTS: Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment. CONCLUSIONS: Melatonin-loaded hydrogel template accelerated formation and enhanced quality of newly formed bone, allowing complete periodontal regeneration. Furthermore, the scaffold prevented overgrowth and entrapment of epithelial cells in furcation defects.

An effectiveness and economic analyses of tricalcium phosphate combined with iliac bone graft versus RhBMP-2 in single-level XLIF surgery in Thailand.

STUDY DESIGN: Retrospective study. OBJECTIVES: To perform effectiveness and economic analyses using data from a retrospective study of patients who underwent XLIF surgery using tricalcium phosphate combined with iliac bone graft (TCP + IBG) or BMP-2 in Thailand. METHODS: Data were collected from retrospective review of the medical charts and the spine registry of Siriraj Hospital, Bangkok, Thailand. The patients were divided into two groups (TCP + IBG group and BMP-2 group). Demographic, perioperative data, radiographic, clinical results, and quality of life related to health were collected and analyzed at 2-year follow-up. All economic data were collected during the perioperative period and presented as total charge, bone graft, implant/instrumentation, operative service, surgical supply, transfusion, medication, anesthesia, laboratory, and physical therapy. RESULTS: Twenty-five TCP + IBG and 30 BMP-2 patients with spondylolisthesis and spinal stenosis as primary diagnosis were included. There were no significant differences in all demographic parameters (gender, age, underlying disease, diagnosis, and level of spine) between these two groups. During the perioperative period, the TCP + IBG group had more mean blood loss and more postoperative complications compared to the BMP-2 group. At 2 years of follow-up, there were no significant differences between the radiographic and clinical outcomes of the TCP + IBG and BMP-2 groups. The fusion rate for TCP + IBG and BMP-2 at 2 years of follow-up was 80% and 96.7%, respectively, and no statistically significant differences were observed. All clinical outcomes (Utility, Oswestry Disability Index, and EuroQol Visual Analog Scale) at 2-year follow-up improved significantly compared to preoperative outcomes, but there were no significant differences between the TCP + IBG and BMP-2 groups, either at preoperatively or at 2-year follow-up. The total charge of TCP + IBG was statistically significantly lower than that of BMP-2. Furthermore, the charges of TCP + IBG and BMP-2 during the perioperative period in Thailand were up to three times less than those in the United States. CONCLUSIONS: Using TCP + IBG as a standalone bone substitution for XLIF surgery with additional posterior instrumentation resulted in significantly lower direct medical charge compared to those using BMP-2 in the perioperative period. However, we could not detect a difference in the long-term radiographic and clinical outcomes of patients with TCP + IBG and BMP-2. These suggest that TCP + IBG may be a valuable alterative bone graft, especially in low- and middle-income countries.

Unidirectional porous beta-tricalcium phosphate as a potential bone regeneration material for infectious bony cavity without debridement in pyogenic spondylitis.

An 81-year-old man was initially diagnosed with T11 osteoporotic vertebral fracture. The fractured vertebral body was filled with unidirectional porous beta-tricalcium phosphate (ß-TCP) granules, and posterior spinal fixation was conducted using percutaneous pedicle screws. However, the pain did not improve, the inflammatory response increased, and bone destructive changes extended to T10. The correct diagnosis was pyogenic spondylitis with concomitant T11 fragility vertebral fracture. Revision surgery was conducted 2 weeks after the initial surgery, the T10 and T11 pedicle screws were removed, and refixation was conducted. After the revision surgery, the pain improved and mobilization proceeded. The infection was suppressed by the administration of sensitive antibiotics. One month after surgery, a lateral bone bridge appeared at the T10/11 intervertebral level. This increased in size over time, and synostosis was achieved at 6 months. Resorption of the unidirectional porous ß-TCP granules was observed over time and partial replacement with autologous bone was evident from 6 months after the revision surgery. Two years and 6 months after the revision surgery, although there were some residual ß-TCP and bony defect in the center of the vertebral body, the bilateral walls have well regenerated. This suggested that given an environment of sensitive antibiotic administration and restricted local instability, unidirectional porous ß-TCP implanted into an infected vertebral body may function as a resorbable bone regeneration scaffold without impeding infection control even without debridement of the infected bony cavity.

Development of bioinspired damage-tolerant calcium phosphate bulk materials.

Improving the damage tolerance and reliability of ceramic artificial bone materials, such as sintered bodies of hydroxyapatite (HAp), that remain in vivo for long periods of time is of utmost importance. However, the intrinsic brittleness and low damage tolerance of ceramics make this challenging. This paper reports the synthesis of highly damage tolerant calcium phosphate-based materials with a bioinspired design for novel artificial bones. The heat treatment of isophthalate ion-containing octacalcium phosphate compacts in a nitrogen atmosphere at 1000°C for 24 h produced an HAp/ß-tricalcium phosphate/pyrolytic carbon composite with a brick-and-mortar structure (similar to that of the nacreous layer). This composite exhibited excellent damage tolerance, with no brittle fracture upon nailing, likely attributable to the specific mechanical properties derived from its unique microstructure. Its maximum bending stress, maximum bending strain, Young's modulus, and Vickers hardness were 11.7 MPa, 2.8 × 10‒2, 5.3 GPa, and 11.7 kgf/mm2, respectively. The material exhibited a lower Young's modulus and higher fracture strain than that of HAp-sintered bodies and sintered-body samples prepared from pure octacalcium phosphate compacts. Additionally, the apatite-forming ability of the obtained material was confirmed in vitro, using a simulated body fluid. The proposed bioinspired material design could enable the fabrication of highly damage tolerant artificial bones that remain in vivo for long durations of time.

ß-Tricalcium Phosphate-Modified Aerogel Containing PVA/Chitosan Hybrid Nanospun Scaffolds for Bone Regeneration.

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of ß-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.

Influence of Scaffold Microarchitecture on Angiogenesis and Regulation of Cell Differentiation during the Early Phase of Bone Healing: A Transcriptomics and Histological Analysis.

The early phase of bone healing is a complex and poorly understood process. With additive manufacturing, we can generate a specific and customizable library of bone substitutes to explore this phase. In this study, we produced tricalcium phosphate-based scaffolds with microarchitectures composed of filaments of 0.50 mm in diameter, named Fil050G, and 1.25 mm named Fil125G, respectively. The implants were removed after only 10 days in vivo followed by RNA sequencing (RNAseq) and histological analysis. RNAseq results revealed upregulation of adaptive immune response, regulation of cell adhesion, and cell migration-related genes in both of our two constructs. However, significant overexpression of genes linked to angiogenesis, regulation of cell differentiation, ossification, and bone development was observed solely in Fil050G scaffolds. Moreover, quantitative immunohistochemistry of structures positive for laminin revealed a significantly higher number of blood vessels in Fil050G samples. Furthermore, µCT detected a higher amount of mineralized tissue in Fil050G samples suggesting a superior osteoconductive potential. Hence, different filament diameters and distances in bone substitutes significantly influence angiogenesis and regulation of cell differentiation involved in the early phase of bone regeneration, which precedes osteoconductivity and bony bridging seen in later phases and as consequence, impacts the overall clinical outcome.

Development and In Vitro Characterization of Antibiotic-Loaded Nanocarriers for Dental Delivery.

The aim of this research work was to formulate and evaluate ciprofloxacin hydrochloride-loaded nanocarriers for treating dental infections and bone regeneration. Periodontal infection is associated with inflammation, soft tissue destruction, and bone loss. The objective of the study was to extract ß tricalcium phosphate (ß-TCP) from coral beach sand using the hydrothermal conversion method and load these nanocarriers with ciprofloxacin hydrochloride. The developed drug-loaded nanocarriers were evaluated for various parameters. In vitro drug-loading studies showed the highest drug loading of 71% for F1 with a drug: carrier ratio compared to plain ciprofloxacin hydrochloride gel. ß-TCP and nanocarriers were evaluated for powder characteristics and the results were found to have excellent and fair flowability. In vitro drug release studies conducted over a period of 5 days confirmed the percentage drug release of 96% at the end of 120 h. Nanocarriers were found to be effective against S. aureus and E. coli showing statistically significant antibacterial activity at (* p < 0.05) significant level as compared to plain ciprofloxacin hydrochloride gel. The particle size of ß-TCP and nanocarriers was found to be 2 µm. Fourier transform infra-red studies showed good compatibility between the drug and the excipients. Differential scanning calorimetry studies revealed the amorphous nature of the nanocarriers as evident from the peak shift. It is obvious from the XRD studies that the phase intensity was reduced, which demonstrates a decrease in crystallinity. Nanocarriers released the drug in a controlled manner, hence may prove to be a better option to treat dental caries as compared to conventional treatments.