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Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

ABSTRACT: Bone defects, especially large ones, are clinically difficult to treat. The development of new bone repair materials exhibits broad application prospects in the clinical treatment of trauma. Bioceramics are considered to be one of the most promising biomaterials owing to their good biocompatibility and bone conductivity. In this study, a self-curing bone repair material having a controlled degradation rate was prepared by mixing calcium citrate, calcium hydrogen phosphate, and semi-hydrated calcium sulfate in varying proportions, and its properties were comprehensively evaluated. In vitro cell experiments and RNA sequencing showed that the composite cement activated PI3K/Akt and MAPK/Erk signaling pathways to promote osteogenesis by promoting the proliferation and osteoblastic differentiation of mesenchymal stem cells. In a rat model with femoral condyle defects, the composite bone cement showed excellent bone repair effect and promoted bone regeneration. The injectable properties of the composite cement further improved its practical applicability, and it can be applied in bone repair, especially in the repair of irregular bone defects, to achieve superior healing.

SUBMITTER: Cheng S

PROVIDER: S-EPMC10193540 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

Cheng Shengwen S Zhao Chen C Liu Senrui S Chen Bowen B Chen Hong H Luo Xuefeng X Wei Li L Du Chengcheng C Xiao Pengcheng P Lei Yiting Y Yan Yonggang Y Huang Wei W

ACS omega 20230501 19

Bone defects, especially large ones, are clinically difficult to treat. The development of new bone repair materials exhibits broad application prospects in the clinical treatment of trauma. Bioceramics are considered to be one of the most promising biomaterials owing to their good biocompatibility and bone conductivity. In this study, a self-curing bone repair material having a controlled degradation rate was prepared by mixing calcium citrate, calcium hydrogen phosphate, and semi-hydrated calc ...[more]

PMID: 37214722

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Project description:BackgroundAs a class of promising bone augmentation materials, bone cements have attracted particular attention. Due to various limitations, the current bone cements are still imperfect. In this study, an injectable pH neutral bioactive bone cement (PSC/CSC) was developed by mixing phosphosilicate bioactive glass (PSC) and α-calcium sulfate hemihydrate (CSH), with the goal of optimizing bone defects repairs.MethodsA range of compositions (PSC/CSC: 10P/90C, 30P/70C, 50P/50C) were developed and their physicochemical properties evaluated. Their bone regeneration ability was compared to those of two widely used bone cements as controls (calcium phosphate cement (CPC) and Genex®) in rabbit femoral condyle bone defect models for 4, 8 and 12 weeks. Based on physicochemical properties and in vivo bone regeneration ability, the PSC/CSC exhibited the best outcomes was selected. Then, in vitro, the effects of selected PSC/CSC, CPC and Genex® extracts on MC3T3-E1 cell proliferation, migration and osteogenesis as well as angiogenesis of HUVECs were examined.ResultsBased on physicochemical properties, the 30P/70C formula exhibited suitable operability and compressive strength (3.5 ± 0.3 MPa), which fulfilled the requirements for cancellous bone substitutes. In vivo, findings from micro-CT and histological analyses showed that the 30P/70C formula better promoted bone regeneration, compared to 10P/90C, 50P/50C, CPC and Genex®. Hence, 30P/70C was selected as the ideal PSC-based cement. In vitro, the 30P/70C extracts showed better promotion of cell viability, alkaline phosphatase (ALP) activity, calcium mineral deposition, mRNA and protein expression levels of osteogenesis in MC3T3-E1 cells, further supporting its superiority. Meanwhile, the 30P/70C extracts also showed better stimulation of HUVECs proliferation and angiogenesis.ConclusionThe new composite cement, 30P/70C, is a favorable bioactive glass-based bone cement with suitable operability, compressive strength and bone regeneration ability.The translational potential of this articleClinically, treatment of large bone defects is still a major challenge for orthopaedic trauma. We showed that 30P/70C has the potential to be clinically used as an injectable cement for rapid bone repairs and reconstruction of critical sized bone defects.

Project description:Calcium phosphate cements (CPCs) have been extensively investigated as scaffolds in bone tissue engineering in light of their chemical composition closely resembling the mineral component of bone extracellular matrix. Yet, the degradation kinetics of many CPCs is slow compared to de novo bone formation. In order to overcome this shortcoming, the use of porogens within CPCs has been suggested as a potential strategy to increase scaffold porosity and promote surface degradation. This study explored the usage of glucose microparticles (GMPs) as porogens for the introduction of macroporosity within CPCs, and characterized the handling properties and physicochemical characteristics of CPCs containing GMPs. Samples were fabricated with four different weight fractions of GMPs (10, 20, 30, and 40%) and two different size ranges (100-150μm and 150-300μm), and were assayed for porosity, pore size distribution, morphology, and compressive mechanical properties. Samples were further tested for their handling properties - specifically, setting time and cohesiveness. Additionally, these same analyses were conducted on samples exposed to a physiological solution in order to estimate the dissolution kinetics of GMPs and its effect on the properties of the composite. GMPs were efficiently encapsulated and homogeneously dispersed in the resulting composite. Although setting times increased for GMP/CPC formulations compared to control CPC material, increasing the Na2HPO4 concentration in the liquid phase decreased the initial setting time to clinically acceptable values (i.e. <15min). Incorporation of GMPs led to the formation of instant macroporosity upon cement setting, and encapsulated GMPs completely dissolved in three days, resulting in a further increase in scaffold porosity. However, the dissolution of GMPs decreased scaffold compressive strength. Overall, the introduction of GMPs into CPC resulted in macroporous scaffolds with good handling properties, as well as designer porosity and pore size distribution via selection of the appropriate size/weight fraction of GMPs. The data demonstrate that GMPs are promising porogens for the production of highly tunable porous CPC scaffolds.Statement of significanceCalcium phosphate cements have shown great promise for the regeneration of bone. However, macropores (>100μm) are required for promoting bone ingrowth. Several studies have investigated methods to generate macroporosity within calcium phosphate cements but many of these methods either affect the cement setting or take weeks or months to generate the maximum porosity. This work offers a new method for generating macroporosity within calcium phosphate cements by utilizing glucose microparticles. The microparticles dissolve in less then 72h, thereby generating scaffolds with maximum porosity in short period of time. The results will offer a new method for generating macroporosity within calcium phosphate cements.

Project description:ObjectivesCalcium phosphate cements (CPCs) are promising for dental and craniofacial repairs. The objectives of this study were to: (1) develop an injectable cell delivery system based on encapsulation of induced pluripotent stem cell-derived mesenchymal stem cells (iPSMSCs) in microbeads; (2) develop a novel tissue engineered construct by dispersing iPSMSC-microbeads in CPC to investigate bone regeneration in an animal model for the first time.MethodsiPSMSCs were pre-osteoinduced for 2 weeks (OS-iPSMSCs), or transduced with bone morphogenetic protein-2 (BMP2-iPSMSCs). Cells were encapsulated in fast-degradable alginate microbeads. Microbeads were mixed with CPC paste and filled into cranial defects in nude rats. Four groups were tested: (1) CPC-microbeads without cells (CPC control); (2) CPC-microbeads-iPSMSCs (CPC-iPSMSCs); (3) CPC-microbeads-OS-iPSMSCs (CPC-OS-iPSMSCs); (4) CPC-microbeads-BMP2-iPSMSCs (CPC-BMP2-iPSMSCs).ResultsCells maintained good viability inside microbeads after injection. The microbeads were able to release the cells which had more than 10-fold increase in live cell density from 1 to 14 days. The cells exhibited up-regulation of osteogenic markers and deposition of minerals. In vivo, new bone area fraction (mean±SD; n=5) for CPC-iPSMSCs group was (22.5±7.6)%. New bone area fractions were (38.9±18.4)% and (44.7±22.8)% for CPC-OS-iPSMSCs group and CPC-BMP2-iPSMSCs group, respectively, 2-3 times the (15.6±11.2)% in CPC control at 12 weeks (p<0.05). Cell-CPC constructs accelerated scaffold resorption, with CPC-BMP2-iPSMSCs having remaining scaffold material that was 7-fold less than CPC control.SignificanceNovel injectable CPC-microbead-cell constructs promoted bone regeneration, with OS-iPSMSCs and BMP2-iPSMSCs having 2-3 fold the new bone of CPC control. Cell delivery accelerated scaffold resorption, with CPC-BMP2-iPSMSC having remaining scaffold material that was 7-fold less than CPC control. Therefore, CPC-microbead-iPSMSC is a promising injectable material for orthopedic, dental and craniofacial bone regenerations.

Dataset Information

Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

Publications

Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

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