Porous Β-tricalcium Phosphate Research Articles

3D printing of multi-scale porous β-tricalcium phosphate scaffolds: Mechanical properties and degradation

Processing-structure-property relationships of 3D-printed multi-scale porous ceramics were investigated. Direct ink writing (DIW) of oil-templated colloidal pastes produced hierarchically porous beta-tricalcium phosphate (TCP) scaffolds. Print architecture and microporosity within filaments were varied, mimicking bone structure. The scaffolds exhibited 60–70 % porosity with interconnected macropores 300–700 μm and microporosity within the filaments at the 10 micron-scale. Varying surfactant and oil concentrations created two micro-pore morphologies – bubble-like pores (emulsion) and channel-like pores (capillary suspension). Emulsion scaffolds were stronger, stiffer and more reliable than capillary suspension scaffolds under both compression and bending. Reducing nozzle diameter and inter-filament distance improved strength and stiffness, at lower density. Immersed at physiological pH, the hierarchically porous TCP scaffolds' strength and modulus degraded at a moderate rate suitable for bone tissue engineering (BTE). Mechanical behavior can be controlled by manipulating process parameters which influence the material's structure. These properties were comparable with trabecular bone, promising for BTE.

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

Porous β-tricalcium phosphate (Ca3(PO4)2; β-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 β-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 β-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.

Use of Unidirectional Porous β-Tricalcium Phosphate in the Tibial Tunnel for Anterior Cruciate Ligament Reconstruction: A Case Series.

Bone defects in the tibial tunnel for anterior cruciate ligament (ACL) reconstruction can cause adverse events. The unidirectional porous tricalcium β-phosphate (UDPTCP) has the potential to be used as a filling substitute for bone defects. In this case series, we present the first nine cases in which UDPTCP was used as a bone substitute in the tibial tunnel during ACL reconstruction. The patients comprised six males and three females, with an average age of 32 years (range: 16-50 years). A cylindrical UDPTCP measuring 10 x 20 mm was molded to fit the tibial tunneland then implanted. At the one-year postoperative follow-up, none of the patients demonstrated any complications, and bone remodeling was observed on radiographs. Therefore, UDPTCP may provide a safe and reliable filling substitute for the tibial tunnel in ACL reconstruction.

Branched Channels in Porous β-Tricalcium Phosphate Scaffold Promote Vascularization.

Rapid and efficient vascularization is still considerably challenging for a porous β-tricalcium phosphate (β-TCP) scaffold to achieve. To overcome this challenge, branched channels were created in the porous β-TCP scaffold by using 3D printing and a template-casting method to facilitate the instant flow of blood supply. Human bone mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were seeded in the channeled porous scaffolds and characterized through a double-stranded DNA (dsDNA) assay, alkaline phosphatase (ALP) assay, and cell migration. Channeled porous β-TCP scaffolds were then implanted in the subcutaneous pockets of mice. Histological staining and immunohistochemical staining on vascularization and bone-related markers were carried out on the embedded paraffin sections. Results from in vitro experiments showed that branched channels significantly promoted HUVECs' infiltration, migration, proliferation, and angiogenesis, and also promoted the proliferation and osteogenesis differentiation of hBMSCs. In vivo implantation results showed that, in the early stage after implantation, cells significantly migrated into branched channeled scaffolds. More matured blood vessels formed in the branched channeled scaffolds compared to that in nonchanneled and straight channeled scaffolds. Beside promoting vascularization, the branched channels also stimulated the infiltration of bone-related cells into the scaffolds. These results suggested that the geometric design of branched channels in the porous β-TCP scaffold promoted rapid vascularization and potentially stimulated bone cells recruitment.

The bone morphogenetic protein 2 analogue L51P enhances spinal fusion in combination with BMP2 in an in vivo rat tail model

Bone morphogenic protein 2 (BMP2) is known to induce osteogenesis and is applied clinically to enhance spinal fusion despite adverse effects. BMP2 needs to be used in high doses to be effective due to the presence of BMP2 inhibitors. L51P is a BMP2 analogue that acts by inhibition of BMP2 inhibitors. Here, we hypothesized that mixtures of BMP2 and L51P could achieve better spinal fusion outcomes regarding ossification. To test whether mixtures of both cytokines are sufficient to improve ossification, 45 elderly Wistar rats (of which 21 were males) were assigned to seven experimental groups, all which received spinal fusion surgery, including discectomy at the caudal 4–5 level using an external fixator and a porous β-tricalcium phosphate (βTCP) carrier. These βTCP carriers were coated with varying concentrations of BMP2 and L51P. X-rays were taken immediately after surgery and again six and twelve weeks post-operatively. Histological sections and µCT were analyzed after twelve weeks. Spinal fusion was assessed using X-ray, µCT and histology according to the Bridwell scale by voxel-based quantification and a semi-quantitative histological score, respectively. The results were congruent across modalities and revealed high ossification for high-dose BMP2 (10 µg), while PBS induced no ossification. Low-dose BMP2 (1 µg) or 10 µg L51P alone did not induce relevant bone formation. However, all combinations of low-dose BMP2 with L51P (1 µg + 1/5/10 µg) were able to induce similar ossificationas high-dose BMP2. These results are of high clinical relevance, as they indicate L51P is sufficient to increase the efficacy of BMP2 and thus lower the required dose for spinal fusion. Statement of SignificanceSpinal fusion surgery is frequently applied to treat spinal pathologies. Bone Morphogenic Protein-2 (BMP2) has been approved by the U .S. Food and Drug Administration (FDA-) and by the “Conformité Européenne” (CE)-label. However, its application is expensive and high concentrations cause side-effects. This research targets the improvement of the efficacy of BMP2 in spinal fusion surgery.

Preparation and Evaluation of Cements Using Spherical Porous β-Tricalcium Phosphate Granules

Preparation and Evaluation of Cements Using Spherical Porous β-Tricalcium Phosphate Granules

Characterization of porous β-tricalcium phosphate fabricated by physical foaming with a nonionic surfactant: Effect of adding a thickener

Characterization of porous β-tricalcium phosphate fabricated by physical foaming with a nonionic surfactant: Effect of adding a thickener

The Efficiency of Highly Porous β-Tricalcium Phosphate With Bone Marrow Aspirate Concentrate in Midfoot Joint Arthrodesis.

Nonunion is one of the most common and devastating complications following midfoot joint arthrodesis. Many different types of bone grafts and bone substitutes have been used to promote osseous fusion. However, there is no consensus on the gold standard bone grafting material and whether biologic materials should be used alone or in combination. The purpose of this study is to investigate the efficiency of highly porous β-tricalcium phosphate (β-TCP) with bone marrow aspirate concentrate (BMAC) in midfoot joint arthrodesis. This retrospective comparative study included patients who underwent midfoot joint arthrodesis using compression screws. Patients were classified into 2 groups: arthrodesis with highly porous β-TCP and BMAC (group A) and arthrodesis without them (group B). The osseous union rate was compared between the 2 groups. A total of 44 patients (46 feet) including 89 joints were included in this study. There was a significant difference in the union rate between the 2 groups: 91.5% (43/47 joints) in arthrodesis with highly porous β-TCP and BMAC (group A) and 76.2% (32/42 joints) in arthrodesis without highly porous β-TCP and BMAC (group B; P = .048). This study investigated the efficiency of highly porous β-TCP and BMAC to promote bony healing in midfoot joint arthrodesis. A significantly higher union rate was shown when arthrodesis was performed with highly porous β-TCP and BMAC, compared with arthrodesis performed without them. We suggest that highly porous β-TCP and BMAC can be a viable and effective adjunct to the fixation in midfoot joint arthrodesis. Level III: Retrospective comparative analysis.

Open reduction and Kirschner wire fixation method using a cylindrical block of unidirectional porous β-tricalcium phosphate for tongue-shaped calcaneal fracture: Report of three cases

The artificial bone grafts are performed on the defect after reduction of the calcaneal fracture. Generally, it is an artificial bone graft with an implant, and there are a few reports of an artificial bone graft without an implant. We report three cases (42-year-old male, 67-year-old male, 21-year-old female) of a tongue-shaped calcaneal fracture treated using a cylindrical unidirectional porous β-tricalcium phosphate artificial bone (Affinos®, Kurare co Ltd., Hyougo, Japan) to surgically repair bone defects after reduction. The bone defect is often observed when fracture is reduced in calcaneal fracture. There were significant bone defects, which were then fixed using Affinos® (forming a cylindrical shape block; diameter 10 mm x height 20 mm) to support the bone fragment, an artificial β-tricalcium phosphate bone with a porosity of 57 % (pore size 25–300 μm), characterized by a novel unidirectional porous structure. Postoperative early rehabilitation started with partial load from 5 weeks after surgery and was full weight bearing at 9 weeks after surgery. There was no correction loss and good bone fusion was obtained. By 12 months postoperatively, patients were able to be walking without pain and absorption and bone fusion around the artificial bone were observed maintaining the morphology immediately after reduction. The result was a good clinical result of one excellent (92 points) and two good (81 and 84 points) 1 year after surgery in the postoperative AOFAS Ankle-Hindfoot Scale. Affinos® has a frost-like structure, which endows it with good tissue invasive properties because of the capillary effect. Moreover, it has excellent osteoconduction capability. In these 3 cases, Affinos® showed good strength, affinity, absorption, and bone substitution in a tongue-shaped calcaneal fracture. Further prospective studies are required to confirm our findings.

Efficacy of platelet-rich plasma impregnation for unidirectional porous β-tricalcium phosphate in lateral lumbar interbody fusion: study protocol for a prospective controlled trial

BackgroundThe use of platelet-rich plasma has been increasing in spinal fusion surgery. However, the efficacy of platelet-rich plasma in lateral lumbar interbody fusion is unclear. In Japan, Affinos,® (Kuraray Co., Tokyo, Japan), a β-tricalcium phosphate artificial bone, has been increasingly used for spinal fusion. The purpose of this trial is to demonstrate whether Affinos® impregnated with platelet-rich plasma can achieve a higher fusion rate and better clinical outcomes than Affinos® alone.MethodsThe current study is a prospective randomized controlled trial. This trial will include consecutive patients scheduled for lateral lumbar interbody fusion. An intervertebral cage for lateral lumbar interbody fusion has two spaces for bone grafts. As a consequence, two bone grafts are inserted at each intervertebral level. In this study, an artificial bone with platelet-rich plasma will be inserted into one space, and an artificial bone without platelet-rich plasma will be inserted into the other space. We will compare the fusion rates between the bone grafts with and without platelet-rich plasma. Our primary endpoint will be the interbody fusion rate at 1 year after surgery.DiscussionThis trial will verify the efficacy of platelet-rich plasma with Affinos® for bony fusion in lateral lumbar interbody fusion. It will also provide substantial evidence for the effectiveness and safety of platelet-rich plasma in spinal fusion surgery.Trial registrationJapan Registry of Clinical Trials (jRCT) jRCTb032200199. First registered on 13 November 2020. jRCT is approved as a member of the Primary Registry Network of WHO ICTRP.

Midfoot Joint Arthrodesis Using Compression Plate With Lag Screw Augmenting With Highly Porous β-Tricalcium Phosphate and Bone Marrow Aspirate Concentrate.

There is still a controversy regarding the most optimal fixation instruments and bone graft materials for midfoot joint arthrodesis. We present the results of midfoot joint arthrodesis using compression plate with lag screw augmenting with highly porous β-tricalcium phosphate (β-TCP) and bone marrow aspirate concentrate (BMAC). We performed a retrospective review of patients undergoing midfoot joint arthrodesis using compression plate with lag screw augmenting with highly porous β-TCP and BMAC from January 2014 to May 2019. The radiographic bony union rate was investigated. Postoperative complications and reoperations were also reviewed. A total of 36 patients (37 feet) including 75 joints were available in this study. A high union rate was achieved as of 97.3% in 73 of 75 joints. Nonunion occurred in 2 patients including 2 joints. Other than nonunion, there were no major complications such as deep infection. Minor complications (5 of 75 joints, 6.7%) included hardware irritations. Reoperations were required in 1 patient for revision of arthrodesis and symptomatic hardware removal was performed in all 5 hardware irritation cases. Based on our results, the fixation construct of compression plate with lag screw augmenting with highly porous β-TCP and BMAC is safe and effective for midfoot joint arthrodesis with an excellent union rate and a low complication rate. IV, retrospective case series.

Midfoot Joint Arthrodesis using Compression Plate with Lag Screw Augmenting with Highly Porous β- Tricalcium Phosphate (β-TCP) and Bone Marrow Aspirate Concentrate (BMAC)

Category: Midfoot/Forefoot Introduction/Purpose: There is still a controversy regarding the most optimal fixation instruments and bone graft materials for midfoot joint arthrodesis. We present the results of midfoot joint arthrodesis using compression plate highly porous β-tricalcium phosphate (β-TCP) and bone marrow aspirate concentrate (BMAC). Methods: We performed a retrospective review of patients undergoing midfoot joint arthrodesis using compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) from January 2014 to May 2019. The radiographic bony union rate was investigated. Postoperative complications and reoperations were also noted. A total of 36 patients (37 feet) including 75 joints were available in this study. Results: A high bony union rate was achieved as of 97.3% in 73 out of 75 joints. Nonunion was seen in two patients including two joints: one for 1st TMT joint and the other for medial NC joint. There was no delayed union in this study. Time to radiographic union was 10.5 +- 1.9 (range, 7-15) weeks. A total of five postoperative complications were noted. All of them were related to hardware irritation, and all five patients underwent removal of hardware procedure. There was no major complication such as infection during the follow-up period. Of the two nonunion patients, only one with medial NC joint nonunion underwent a revision arthrodesis surgery. Conclusion: Based on our results, the fixation construct of compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) is safe and effective for midfoot joint arthrodesis with an excellent union rate and a low complication rate.

The Efficiency of Highly Porous β-Tricalcium Phosphate (β-TCP) with Bone Marrow Aspirate Concentrate (BMAC) in Midfoot Joint Arthrodesis

Category: Midfoot/Forefoot Introduction/Purpose: Nonunion is one of the most common and devastating complications following midfoot joint arthrodesis. Many different types of bone grafts and bone substitutes have been used to promote osseous fusion. However, there is no consensus on the gold standard bone grafting material and whether biologic materials should be used alone or in combination. The purpose of this study is to investigate the efficiency of highly porous β-tricalcium phosphate (β-TCP) with Bone Marrow Aspirate Concentrate (BMAC) in midfoot joint arthrodesis. Methods: This retrospective comparative study included patients who underwent midfoot joint arthrodesis using compression screws from January 2014 to May 2019. A total of 44 patients (46 feet) including 89 joints were included in this study. The cohort was then stratified into two groups: 25 patients (26 feet) in arthrodesis with highly porous β-TCP and BMAC (group A) and 19 patients (20 feet) in arthrodesis without highly porous β-TCP and BMAC (group B). The osseous union rate was compared between the two groups. Demographic and operative data including age, sex, body mass index (BMI), smoking, etiology of arthritis, comorbidities such as diabetes mellitus and rheumatoid arthritis, number of joints fixed, use of bone graft or bone substitute, and postoperative midfoot anatomic alignment in the two groups were compared. Results: There was a significant difference in the union rate between the two groups: 91.5 % (43 out of 47 joints) in arthrodesis with highly porous β-TCP and BMAC (group A) and 76.2 % (32 out of 42 joints) in arthrodesis without highly porous β-TCP and BMAC (group B) (P = 0.048). During the follow-up period, a total of four postoperative complications were reported in this study. In group A, two patients developed hardware irritation, and all of them underwent removal of hardware procedure. In group B, one patient had a superficial wound infection, which was resolved completely without further treatment. The other patient in group B developed a deep wound infection with dehiscence, and it was managed with irrigation and debridement followed by vacuum assisted wound closure therapy. Conclusion: This study investigated the efficiency of highly porous β-TCP and BMAC to promote bony healing in midfoot joint arthrodesis. A significantly higher union rate was shown when arthrodesis was performed with highly porous β-TCP and BMAC compared to arthrodesis without them, suggesting that highly porous β-TCP and BMAC can be a viable and effective adjunct to the fixation in midfoot joint arthrodesis.

Cryogenic 3D Printing of w/o Pickering Emulsions Containing Bifunctional Drugs for Producing Hierarchically Porous Bone Tissue Engineering Scaffolds with Antibacterial Capability

How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous β-tricalcium phosphate (β-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO2) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 μm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 μm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of β-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to “kill bacteria first, then induce osteogenesis”. Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.

Establishment and biological effect evaluation of prevascularized porous β-tricalcium phosphate tissue engineered bone

To evaluate the biological effect on vascularization during bone repair of prevascularized porous β-tricalcium phosphate (β-TCP) tissue engineered bone (hereinafter referred to as prevascularized tissue engineered bone), which was established by co-culture of endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) based on tissue engineering technology. EPCs and BMSCs were isolated from iliac bone marrow of New Zealand white rabbits by density gradient centrifugation and differential adhesion method. The cells were identified by immunophenotypic detection, BMSCs-induced differentiation, and EPCs phagocytosis. After identification, the third-generation cells were selected for subsequent experiments. First, in vitro tubule formation in EPCs/BMSCs direct contact co-culture (EPCs/BMSCs group) was detected by Matrigel tubule formation assay and single EPCs (EPCs group) as control. Then, the prevascularized tissue engineered bone were established by co-culture of EPCs/BMSCs in porous β-TCP scaffolds for 7 days (EPCs/BMSCs group), taking EPCs in porous β-TCP scaffolds as a control (EPCs group). Scanning electron microscopy and laser scanning confocal microscopy were used to observe the adhesion, proliferation, and tube formation of cells. Femoral condyle defect models of 12 New Zealand white rabbits were used for implantation of prevascularized tissue engineered bone as the experimental group ( n=6) and porous β-TCP scaffold as the control group ( n=6). The process of vascularization of β-TCP scaffolds were observed. The numbers, diameter, and area fraction of neovascularization were quantitatively evaluated by Microfill perfusion, Micro-CT scanning, and vascular imaging under fluorescence at 4 and 8 weeks. The isolated cells were BMSCs and EPCs through identification. EPCs/BMSCs co-culture gradually formed tubular structure. The number of tubules and branches, and the total length of tubules formed in the EPCs/BMSCs group were significantly more than those in the EPCs group on Matrigel ( P<0.05) after 6 hours. After implanting and culturing in porous β-TCP scaffold for 7 days, EPCs formed cell membrane structure and attached to the material in EPCs group, and the cells attached more tightly, cell layers were thicker, the number of cells and the formation of tubular structures were significantly more in the EPCs/BMSCs group than in the EPCs group. At 4 weeks after implantation, neovascularization was observed in both groups. At 8 weeks, remodeling of neovascularization occurred in both groups. The number, diameter, and area fraction of neovascularization in the experimental group were higher than those in the control group ( P<0.05), except for area fraction at 4 weeks after implantation ( P>0.05). The prevascularized tissue engineered bone based on direct contact co-culture of BMSCs and EPCs can significantly promote the early vascularization process during bone defects repair.

Characterization of bone remodeling of two different porous types of β-tricalcium phosphates: a quantitative site-by-site analysis using computed tomography.

This study compared the process of bone remodeling using spherical porous β-tricalcium phosphate (SPTCP) and unidirectional porous β-tricalcium phosphate (UDPTCP) by quantitative computed tomography (CT) analysis. We retrospectively analyzed the data of 16 patients (4 men, 12 women; age, 43-78years) who underwent medial opening wedge high tibial osteotomy (MOWHTO) and were followed up for 1year postoperatively. Nine patients used SPTCP spacers and seven patients used UDPTCP spacers. CT was performed at 1week, 6months, and 1year postoperatively. CT attenuation values were measured at three sites on the axial slice and sagittal slice, i.e., the superior, center, and inferior sites and the lateral, center, and medial sites for UDPTCP and SPTCP, respectively. CT attenuation values were lower for UDPTCP than for SPTCP in all sites at 6months and 1year postoperatively (p < 0.05). CT attenuation values decreased in the superior and inferior sites for UDPTCP (p < 0.05), and CT attenuation values decreased in the lateral site for both SPTCP and UDPTCP (p < 0.05). The process of bone remodeling differed between the two over a short-term follow-up of 1year postoperatively.

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.

Development of hierarchical porous bioceramic scaffolds with controlled micro/nano surface topography for accelerating bone regeneration

Mimicking hierarchical porous architecture of bone has been considered as a valid approach to promote bone regeneration. In this study, hierarchical porous β-tricalcium phosphate (β-TCP) scaffolds were constructed by combining digital light processing (DLP) printing technique and in situ growth crystal process. Macro/micro hierarchical scaffolds with designed macro pores for facilitating the ingrowth of bone tissue were fabricated by DLP printing. Three types of micro/nano surface topography were obtained by in situ growth crystal process to regulate stem cells behavior. The attachment and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) were strongly dependent on the surface roughness and the specific surface area. The micro/nano surface topography distinctly facilitated the differentiation of rBMSCs by targeting MAPK, STAT and AKT signaling pathways, in which the sodium hydroxide treatment group showed the highest promoting effect. Furthermore, in vivo results of skull defect repair model of rats indicated that hierarchical scaffolds with micro/nano topographies exhibited appealing bone regeneration capacity. The hierarchical porous bioceramic scaffolds constructed by integrating structural design and physical stimulation of the external surface topography have great potential for rapid bone repair via modulation of microenvironmental regulatory pathways at the bone defect site.

Bioresorbable porous β-tricalcium phosphate chelate-setting cements with poly(lactic-co-glycolic acid) particles as pore-forming agent: fabrication, material properties, cytotoxicity, and in vivo evaluation

ABSTRACT Calcium-phosphate cements (CPCs) have been used as bone filling materials in orthopaedic surgery. However, CPCs are set using an acid-base reaction, and then change into stable hydroxyapatite (HAp) in a living body. Therefore, we developed bioresorbable chelate-setting β-tricalcium phosphate (β-TCP) cements based on surface modifications of inositol phosphate (IP6). In order to improve the bioresorbability, we fabricated IP6/β-TCP cements hybridized with poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent. The compressive strengths of the cements with the amounts of 5 and 10 mass% PLGA particles were 23.2 and 22.8 MPa, respectively. There was no significant difference from cements without PLGA (23.4 MPa). The setting times of the cement specimens with PLGA particles (30 min) were a little longer than those without PLGA particles (26.3 min). The lack of cytotoxicity of the cement specimens was confirmed using osteoblast-like cells (MC3T3-E1). Cylindrical defects were made by drilling into the tibia of mini-pigs and injecting the prepared cement pastes into the defects. Twelve weeks after implantation the specimens were stained with toluidine blue and histologically evaluated. Histological evaluation of cement specimens with PLGA particles showed enhanced bioresorbability. Newly-formed bone was also observed inside cement specimens with PLGA particles. The IP6/β-TCP cement specimens with PLGA particles had excellent material properties, such as injectability, compressive strength, high porosity, no cytotoxicity in vitro, bioresorption and bone formation abilities in vivo. Organic-inorganic hybridized CPCs are expected to be valuable as novel biodegradable paste-like artificial bone fillers.

The Effect of Stromal-Derived Factor 1α on Osteoinduction Properties of Porous β-Tricalcium Phosphate Bioceramics.

β-Tricalcium phosphate (TCP) is a type of bioceramic material which is commonly used for hard tissue repair and famous of its remarkable biocompatibility and osteoconductivity with similar composition to natural bone. However, TCP lacks osteoindcutive properties. Stromal-derived factor 1α (SDF-1α) can promote bone regeneration with excellent osteoinduction effect. In this study, SDF-1α was loaded into TCP to investigate the in vitro effects of SDF-1α on the osteoinductive properties of TCP. In vitro studies showed that SDF-1α/TCP scaffold significantly stimulated the expression of osteopontin and osteocalcin. As to the in vivo studies, the rabbit bone defect model showed that SDF-1α stimulated more new bone formation. In conclusion, SDF-1α/TCP bioceramic scaffolds could further promote bone regeneration compared to pure TCP bioceramics.