β-TCP Granules Research Articles

Pore size influence in fabricating DCPD-Coated Porous β-TCP granules: compositional, morphological, and functional group perspective

Pore size influence in fabricating DCPD-Coated Porous β-TCP granules: compositional, morphological, and functional group perspective

Improving bone defect healing using magnesium phosphate granules with tailored degradation characteristics

ObjectivesDental implant placement frequently requires preceding bone augmentation, for example, with hydroxyapatite (HA) or β-tricalcium phosphate (β-TCP) granules. However, HA is degraded very slowly in vivo and for β-TCP inconsistent degradation profiles from too rapid to rather slow are reported. To shorten the healing time before implant placement, rapidly resorbing synthetic materials are of great interest. In this study, we investigated the potential of magnesium phosphates in granular form as bone replacement materials. MethodsSpherical granules of four different materials were prepared via an emulsion process and investigated in trabecular bone defects in sheep: struvite (MgNH4PO4·6H2O), K-struvite (MgKPO4·6H2O), farringtonite (Mg3(PO4)2) and β-TCP. ResultsAll materials except K-struvite exhibited promising support of bone regeneration, biomechanical properties and degradation. Struvite and β-TCP granules degraded at a similar rate, with a relative granules area of 29% and 30% of the defect area 4 months after implantation, respectively, whereas 18% was found for farringtonite. Only the K-struvite granules degraded too rapidly, with a relative granules area of 2% remaining, resulting in initial fibrous tissue formation and intermediate impairment of biomechanical properties. Significance:We demonstrated that the magnesium phosphates struvite and farringtonite have a comparable or even improved degradation behavior in vivo compared to β-TCP. This emphasizes that magnesium phosphates may be a promising alternative to established calcium phosphate bone substitute materials.

Carbonate apatite versus β-tricalcium phosphate for rat vertical bone augmentation: A comparison of bioresorbable bone substitutes using polytetrafluoroethylene tubes.

This study radiologically and histologically compared two bioresorbable bone substitutes with different compositions carbonate apatite (Cytrans® Granules; CGs) and β-tricalcium phosphate (β-TCP) for vertical bone augmentation on a rat skull using a polytetrafluoroethylene (PTFE) tubes. This PTFE tube was placed at the center of the skull, fixed with Super Bond, and augmented with CGs or β-TCP granules. Specimens with surrounding tissue were harvested at 4, 8, and 12 weeks postoperatively, and radiological and histological evaluations were performed. The bone volume to total volume ratio (BV/TV) of the β-TCP-implanted group was markedly higher than that of the CG-implanted group at 4 and 12 weeks postoperatively. Compared to CGs, β-TCP exhibited the ability to form blood vessels into the graft material for a short period after transplantation, as well as an elevated production of collagen into β-TCP granules during the bone formation process.

Phosphorylated pullulan promotes calcification during bone regeneration in the bone defects of rat tibiae.

The current study aimed to evaluate bone tissue regeneration using a combination of β-tricalcium phosphate (βTCP) and phosphorylated pullulan (PPL, a phosphate-rich polysaccharide polymer consisting of maltotriose units). Round defects of 2mm diameter were created in the arterial center of rat tibiae, which were further treated with vehicle (control group), βTCP (βTCP group), or βTCP + PPL (βTCP + PPL group) grafts. The control specimens without bone grafts exhibited rapid bone formation after 1week; however, the regenerated bone was not resorbed until 4weeks. In contrast, βTCP-grafted specimens exhibited fewer but thicker trabeculae, whereas the βTCP + PPL group displayed many fine trabeculae at 4weeks. In the βTCP + PPL group, new bone was associated with the βTCP granules and PPL. Similarly, PHOSPHO1-positive osteoblasts were localized on the βTCP granules as well as the PPL. On the other hand, TRAP-reactive osteoclasts predominantly localized on newly-formed bone and βTCP granules rather than on the PPL. No significant differences were observed in the expression of Alp, Integrin αv, Osteopontin, Osteocalcin, and Dmp-1 in PPL-treated MC3T3-E1 osteoblastic cells, suggesting that PPL did not facilitate osteoblastic differentiation. However, von Kossa staining identified abundant needle-like calcified structures extending inside the PPL. Furthermore, transmission electron microscopy (TEM) revealed many globular structures identical to calcified nodules. In addition, calcified collagen fibrils were observed in the superficial layer of the PPL. Thus, PPL may serve as a scaffold for osteoblastic bone formation and promotes calcification on its surface. In conclusion, we speculated that βTCP and PPL might promote bone regeneration and could be integrated into promising osteoconductive materials.

球状多孔質β型リン酸三カルシウム顆粒を用いたセメントの作製と評価

Calcium phosphate cements (CPCs) with macropores and micropores for high bone regeneration ability are desired. CPCs with macropores and micropores which were prepared by combining porous granules have been reported. In this study, the cement system composed of β-tricalcium phosphate (β-TCP) granules and phosphoric acid solution was selected, and the effects of the characteristics of granules on the microstructures and properties of the cements were examined. The spherical porous β-TCP granules with high porosity and irregular porous β-TCP granules with low porosity were prepared, and they were mixed with a phosphoric acid solution. When the spherical porous granules with high porosity were used, the granules were packed uniformly in the cement, and the size distribution of the macropores formed among the granules was narrower than that of the cement prepared using the irregular porous β-TCP granules with low porosity. The cement with high porosity can be obtained from the spherical porous granules with high porosity. The cement prepared using the spherical granules with high porosity showed lower compressive strength and higher dissolution rate than the cement prepared using irregular granules with low porosity.

Evaluation of Two Configurations of Hydroxyapatite and Beta-Tricalcium Phosphate in Sinus Grafts with Simultaneous Implant Installation: An Experimental Study in Rabbits.

This study aimed to evaluate peri-implant bone formation in rabbits after sinus grafting mediated by hydroxyapatite and beta-tricalcium phosphate (HA + β-TCP) in granule or paste configurations, concomitant with immediate implant installation. Thirty-four rabbit maxillary sinuses were grafted with HA + β-TCP, half of which were applied in a granule and half in a paste composition. Implant placement was performed simultaneously. At 7 and 40 days postoperatively, the animals were euthanized, and samples were prepared for tomographic, microtomographic, histological, histometric (hematoxylin and eosin staining, HE), and immunohistochemical (labeling of transcription factor Runx-2 [RUNX2], vascular endothelial growth factor [VEGF], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analysis. Implant removal torque was also measured. On tomography, maintenance of sinus membrane integrity was observed in both the groups. Higher values of morphometric parameters evaluated by micro-CT were found in the "paste group" after seven days. At 40 days, there were no significant differences between the groups in most of the microtomographic parameters evaluated. In histological sections stained with HE, a higher percentage of newly formed bone was observed in the "granule group" after 40 days. Similar positive immunolabeling was observed for both RUNX2 and OCN in both the experimental groups. TRAP immunolabeling was similar in both groups as well. VEGF labeling increased in the "granule group", indicating a higher osteoconductive potential in this biomaterial. Similar removal torque values were observed in both groups. Thus, the two HA + β-TCP configurations showed similar healing patterns of simultaneously installed implants adjacent to sinus floor elevation. However, significantly higher bone values were observed for the "granule configuration". The HA + β-TCP granules and paste presentations showed favorable long-term healing results, with bone formation in similar quantities and quality adjacent to the implants.

Bone tissue 3D bioprinting in regenerative dentistry through the perspective of the diamond concept of healing: A narrative review.

Three-dimensional bioprinting technology appears to be a promising solution for the treatment and reconstruction of a wide range of maxillofacial bone defects. In this review, the authors discuss different bioprinting solutions and options in the context of the 4 factors of bone healing: structures or scaffolds, osteogenic cells, growth factors, and stabilization (diamond concept of healing), as well as the influence of a 5th factor - vascularization. Bone is a complex tissue; hence, bone bioprinting may require different technical approaches and mixed methods. Ultraviolet (UV) crosslinkable hydrogels, such as gelatin methacryloyl (GelMA), are among the most promising bioinks; they are enhanced by hydroxyapatite or 1-2.5 mm beta-tricalcium phosphate (β-TCP) granules and porous scaffolds with recommended pore sizes greater than 300 μm. The advantages of mesenchymal stem cells (MSCs) are their significant availability, low tumorigenicity, and great potential for differentiation into osteoblasts or endothelial cells (ECs). Although growth factors require advanced delivery systems, they provide excellent improvement in the functionality of printed tissues. A proper vasculature system supplies cells with oxygen and nutrients, removes waste products, promotes osteogenesis, prevents ischemic necrosis, and improves the mechanical properties of bone. With all of these aspects perfectly balanced and working in synergy, the clinical use of bioprinting is only a matter of time.

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 (β-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 2weeks 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 6months. Resorption of the unidirectional porous β-TCP granules was observed over time and partial replacement with autologous bone was evident from 6months after the revision surgery. Two years and 6months after the revision surgery, although there were some residual β-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 β-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.

A fully ingrowing implant for cranial reconstruction: Results in critical size defects in sheep using 3D-printed titanium scaffold.

Current alloplastic materials such as PMMA, titanium or PEEK don't show relevant bone ingrowth into the implant when used for cranioplasty, ceramic implants have the drawback being brittle. New materials and implant designs are urgently needed being biocompatible, stable enough for cranioplasty and stimulating bone formation. In an in vivo critical size sheep model circular cranial defects (>2.4cm) were covered with three different types of a 3D-printed porous titanium scaffolds with multidirectional, stochastically distributed architecture (uncoated scaffold, hydroxyapatite-coated scaffold, uncoated scaffold filled with a calcium phosphate bone cement paste containing β-TCP granules). An empty titanium mesh served as control. Among the different investigated setups the hydroxyapatite-coated scaffolds showed a surprisingly favourable performance. Push-out tests revealed a 2.9 fold higher force needed in the hydroxyapatite-coated scaffolds compared to the mesh group. Mean CT density at five different points inside the scaffold was 2385HU in the hydroxyapatite-coated group compared to 1978HU in the uncoated scaffold at nine months. Average lateral bone ingrowth after four months in the hydroxyapatite-coated scaffold group was up to the implant center, 12.1mm on average, compared to 2.8mm in the control group covered with mesh only. These properties make the investigated scaffold with multidirectional, stochastically distributed structure superior to all products currently on the market. The study gives a good idea of what future materials for cranioplasty might look like.

Effects of ultraviolet irradiation on beta-tricalcium phosphate as a bone graft substitute.

Surface modification of various materials using ultraviolet (UV) irradiation improves their wettability. The purpose of this study was to investigate the wettability of a β-tricalcium phosphate (TCP) surface and the composition changes and bioactivity of β-TCP after UV irradiation. We applied 172nm UV treatment to a β-TCP surface and measured the contact angle before and after UV irradiation. Energy-dispersive X-ray and Fourier transform infrared spectroscopy examinations were performed on the β-TCP disk with or without UV treatment. In an adhesion test of bone marrow cells using β-TCP disks with and without UV irradiation, cell attachment was measured 10, 30, 50, and 70h after β-TCP insertion. UV-irradiated β-TCP osteogenesis and absorption of bone substitutes were evaluated using hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining in a rabbit sinus model. The contact angle on the TCP surface decreased from 70° to 10° owing to UV irradiation. Conversely, UV irradiation did not change the composition of carbon, oxygen, and phosphorus. In the cell adhesion test, UV-irradiated β-TCP significantly increased cell adhesion compared with UV-unirradiated β-TCP after 10 to 30h of culture. In the rabbit sinus model, TRAP staining showed that UV-irradiated β-TCP significantly increased the number of TRAP-positive cells compared with unirradiated β-TCP granules in the central part of β-TCP. Our results indicate that the UV irradiation of β-TCP improves its clinical utility for surgical bone augmentation in the oral and maxillofacial region.

Feasibility study on surface morphology regulation of β-tricalcium phosphate bone graft for enhancing cellular response

Beta-tricalcium phosphate (βTCP) granules are commonly used as an artificial bone graft material. Meanwhile, the surface morphology of the bone graft is an important factor for cellular response. In this study, feasibility study on surface morphology regulation of βTCP bone graft for enhancing cellular response were investigated. The regulation was achieved on the basis of a multistep heating process. Briefly, initial heat treatment of βTCP granules at 1300 °C for 12 h resulted in fabrication of alpha-tricalcium phosphate (αTCP) granules with interconnected micropores. In the second heat treatment, exposure of αTCP granules to 100% relative humidity at 100 °C resulted in partial hydrolysis of αTCP, leading to the fabrication of needle-like calcium-deficient hydroxyapatite (cdHAp) crystals on the αTCP surface. After the third heat treatment at 1100 °C, both cdHAp and αTCP converted back to βTCP, and interconnected micropores with a roughened surface structure were formed. In vitro cell evaluation demonstrated that βTCP granules obtained by the series of heat treatments exhibited 24 times higher cell proliferation at day 9, and four times higher alkaline phosphatase activity compared with untreated βTCP granules. Therefore, we concluded that regulation of surface morphology by a series of heat treatments is useful for improving cellular response to βTCP bone grafting materials.

Utility of Thermal Cross-Linking in Stabilizing Hydrogels with Beta-Tricalcium Phosphate and/or Epigallocatechin Gallate for Use in Bone Regeneration Therapy.

β-tricalcium phosphate (β-TCP) granules are commonly used materials in dentistry or orthopedic surgery. However, further improvements are required to raise the operability and bone-forming ability of β-TCP granules in a clinical setting. Recently, we developed epigallocatechin gallate (EGCG)-modified gelatin sponges as a novel biomaterial for bone regeneration. However, there is no study on using the above material for preparing hydrogel incorporating β-TCP granules. Here, we demonstrate that vacuum heating treatment induced thermal cross-linking in gelatin sponges modified with EGCG and incorporating β-TCP granules (vhEc-GS-β) so that the hydrogels prepared from vhEc-GS-β showed high stability, β-TCP granule retention, operability, and cytocompatibility. Additionally, microcomputed tomography morphometry revealed that the hydrogels from vhEc-GS-β had significantly higher bone-forming ability than β-TCP alone. Tartrate-resistant acid phosphatase staining demonstrated that the number of osteoclasts increased at three weeks in defects treated with the hydrogels from vhEc-GS-β compared with that around β-TCP alone. The overall results indicate that thermal cross-linking treatment for the preparation of sponges (precursor of hydrogels) can be a promising process to enhance the bone-forming ability. This insight should provide a basis for the development of novel materials with good operativity and bone-forming ability for bone regenerative medicine.

In vivo evaluation of bone regeneration behavior of novel β-tricalcium phosphate/layered double hydroxide nanocomposite granule as bone graft substitutes.

This study was based on in vivo assessment of bone regeneration capacity of synthesized porous β-tricalcium phosphate (β-TCP) nanocomposite granules and aimed to explore the effects of fabricated β-TCP granules reinforced with layered double hydroxides (LDH) nanoclay compared to β-TCP granules, in terms of osteoconductivity and biodegradability. Granules with diameters of 2-3 mm were implanted into cavities drilled in rabbit distal femur and were left in situ for up to 3months. The mechanical study demonstrated that the presence of LDH nanoparticles in β-TCP granules resulted in a significant increase in compressive modulus from 174.4 to 231.4MPa, while the porosity was constant at 76%-80%. The results revealed that the obtained granules showed no cytotoxicity. In this study, x-ray radiographic, micro-computed tomography, and histological staining analysis were taken to evaluate the percentage of bone ingrowth and biodegradability of the porous granules. The results exhibited that both granules support bone regeneration and also the amount of new bone formation in the bone defect filled with both granules was almost six times higher than the empty defects. Although no significant difference in bone formation for two different granules was observed, a higher biodegradability was detected in β-TCP granules in comparison to β-TCP/LDH granules. Overall, the addition of LDH nanoclay (10%) enhanced the physicochemical and mechanical properties of β-TCP granules while it is biological and osteoconductity properties have been maintained and its biodegradation rate has been decreased.

Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation.

We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-tricalcium phosphate (β-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 μg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 μg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.

Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics.

Various stresses latently induce cellular senescence that occasionally deteriorates the functioning of surrounding tissues. Nevertheless, little is known about the appearance and function of senescent cells, caused by the implantation of beta-tricalcium phosphate (β-TCP)—used widely in dentistry and orthopedics for treating bone diseases. In this study, two varying sizes of β-TCP granules (<300 μm and 300–500 μm) were implanted, and using histological and immunofluorescent staining, appearances of senescent-like cells in critical-sized bone defects in the calvaria of Sprague Dawley rats were evaluated. Parallelly, bone formation in defects was investigated with or without the oral administration of senolytics (a cocktail of dasatinib and quercetin). A week after the implantation, the number of senescence-associated beta-galactosidase, p21-, p19-, and tartrate-resistant acid phosphatase-positive cells increased and then decreased upon administrating senolytics. This administration of senolytics also attenuated 4-hydroxy-2-nonenal staining, representing reactive oxygen species. Combining senolytic administration with β-TCP implantation significantly enhanced the bone formation in defects as revealed by micro-computed tomography analysis and hematoxylin-eosin staining. This study demonstrates that β-TCP granules latently induce senescent-like cells, and senolytic administration may improve the bone-forming ability of β-TCP by inhibiting senescence-associated mechanisms.

Combining autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression improves short-term outcomes in early avascular necrosis of the femoral head: a prospective, randomized, comparative study

BackgroundTreatment of avascular necrosis of the femoral head (ANFH) in young patients remains a clinical challenge. A current controversy is whether hip-preserving surgery results in better outcomes. The adverse effects of hip-preserving surgery are associated with the fill material for the necrotic areas. This study aims to evaluate the early effects of autologous bone marrow buffy coat (BBC) and angioconductive bioceramic rod (ABR) grafting with advanced core decompression (ACD) on early ANFH.MethodsForty-four (57 hips) patients with early ANFH from 2015 to 2020 were recruited for this study. They were randomized into two groups: group A received ACD, BBC, and ABR grafting; group B received treatment of ACD with β-tricalcium phosphate (β-TCP) granules and ABR grafting. The outcomes were assessed using the Harris Hip Scores (HHS) and survival rate analysis. The follow-up endpoint was defined as conversion to total hip arthroplasty (THA).ResultsForty patients (51 hips) were ultimately included in this study for analysis. Compared with group B, patients in group A had higher postoperative function score (P = 0.032) and postoperative Harris Hip Scores (HHS) (P = 0.041). Kaplan-Meier analysis showed a trend that the survivorship of the femoral head was higher in group A than in group B.ConclusionThe short-term follow-up results showed that the autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression is effective in the treatment of early ANFH.Trial registrationChictr.org.cn, ChiCTR2000039595. Retrospectively registered on 11 February 2015.

Fabrication and Evaluation of Layered Double Hydroxide-Enriched ß-Tricalcium Phosphate Nanocomposite Granules for Bone Regeneration: In Vitro Study.

One of the most important challenges facing tissue engineering researches is the scaffold design with optimum physical and mechanical properties for growth and proliferation of cells, and tissue formation. The aim of this study was to produce a novel nanocomposite containing β-tricalcium phosphate and layered double hydroxide (β-TCP-LDH) and analyzing the capacity of its osteogenic activity in vitro. In this paper, β-tricalcium phosphate and layered double hydroxide powders were synthesized by co-precipitation processes. Then, the porous nanocomposite granules were prepared by the polyurethane sponge replication method. In this study, four kinds of β-TCP granules containing LDHs nanoparticles (ranging from 0.1 to 10wt%) have been prepared. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analyses were selected to study the phase structure, morphology, and phase distribution, respectively. Physicochemical characterizations demonstrated that the granules were synthesized successfully. Interconnected macro pores ranging over 200-500μm were observed for all kinds of granules. SEM micrographs showed that human mesenchymal stem cells (hMSCs) were attached to the surfaces of the granules and proliferated in good shape. The results warranted that the synthesized granules exhibited good biocompatibility and mineralization. Based on the results of compressive strength and porosity tests, the most suitable type of granule is β-TCP/LDH 10wt% with 77% porosity and compressive modulus of 231.4MPa, which can be utilized in bone tissue engineering. To our knowledge, layered double hydroxides have not previously been incorporated into tricalcium phosphate granules for bone grafting. Also, this study is the first report on the effects of LDH on the mechanical properties and porosity of β-TCP granules. Our results demonstrated that β-TCP/LDH nanocomposite granule has a great potential for bone defects regeneration and tissue engineering applications.

Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation.

Gene-activated matrix (GAM) has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be established. In this study, we investigated whether an atelocollagen-based GAM containing naked-plasmid (p) DNAs encoding microRNA (miR) 20a, which may promote osteogenesis in vivo via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells (MSCs), facilitates rat cranial bone augmentation. First, we confirmed the osteoblastic differentiation functions of generated pDNA encoding miR20a (pmiR20a) in vitro, and its transfection regulated the expression of several of target genes, such as Bambi1 and PPARγ, in rat bone marrow MSCs and induced the increased expression of BMP4. Then, when GAMs fabricated by mixing 100 μl of 2% bovine atelocollagen, 20 mg β-TCP granules and 0.5 mg (3.3 μg/μl) AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface, the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation, as were upregulation of VEGFs and BMP4 expressions at the early stages of transplantation. Thus, GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.

Self-setting β-tricalcium phosphate granular cement at physiological body condition: effect of citric acid concentration as an inhibitor

The aim of this study is to investigate the effect of citric acid (CA) concentration as an inhibitor on the properties of β-tricalcium phosphate (β-TCP) granular cement. In this study, β-TCP granules were exposed to an acidic calcium phosphate solution containing 0.01 mol/L, 0.10 mol/L, and 1.00 mol/L of CA at physiological body conditions for 10 min. These specimens were denoted as 0.01 mol/L CA, 0.10 mol/L CA, and 1.00 mol/L CA, and its properties were characterized throughout the study. Physical appearance results showed that increasing citric acid concentration in an acidic calcium phosphate solution up to 1.00 mol/L reduced the self-setting ability of β-TCP granules. Meanwhile, compositional and morphological analyses showed the amount of dicalcium phosphate dihydrate (DCPD) crystals that precipitated and interlocked between β-TCP granules decreased when the concentration of citric acid increased. The decreasing trend of DCPD formation in set specimens increased its porosity and reduced the compression strength up to 27.4%. Therefore, these findings evinced that by altering the concentration of citric acid in an acidic calcium phosphate solution, the setting reaction of β-TCP granules at physiological body condition was inhibited.

Faster bone union progression and less sclerosis at the osteotomy margin after medial opening-wedge high tibial osteotomy using highly porous β-tricalcium phosphate granules versus allogeneic bone chips: A matched case–control study

BackgroundThis study compared bone union progression using highly porous (80% porosity) β-tricalcium phosphate (β-TCP) granules or allogeneic bone chips in the gap created by medial opening-wedge high tibial osteotomy (MOWHTO). MethodsThe study population consisted of 54 patients who received MOWHTO with locking plate fixation: 27 patients using highly porous β-TCP granules, and 27 age- and sex-matched patients using allogeneic bone chips. Bone union progression was evaluated 1, 3, 6, and 12 months postoperatively. The presence of radiographic sclerosis at the osteotomy margin was also assessed. ResultsAmong all patients, the highest degree of bone union observed 12 months postoperatively was grade 4. As postoperative time passed, bone union progression of highly porous β-TCP granules increased linearly and was statistically significant compared with that of cancellous allogeneic bone chips (P = 0.014). The presence of radiographic sclerosis at the osteotomy margin was significantly less common in the β-TCP group than in the allograft group (P = 0.003) and was the strongest predictor of delayed progress of bone union (odds ratio = 6.16, P = 0.006). ConclusionsPatients who underwent MOWHTO using highly porous β-TCP granules had faster new bone remodeling, less radiographic sclerosis at the osteotomy margin, and no inferior clinical outcome compared with allogeneic bone chips, as determined at the 1-year follow up. The presence of radiographic sclerosis at the osteotomy margin in patients undergoing MOWHTO using allogeneic bone or synthetic bone substitute may indicate delayed progress of bone union.