Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats (original) (raw)
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Journal of Research of the National Institute of Standards and Technology, 2001
Research on calcium phosphate chemistry at NIST led to the discovery of the worlds first self-hardening calcium phosphate cements (CPC) in 1987. Laboratory, animal, and clinical studies were conducted to develop CPC into clinically useful biomaterials. The combination of self-hardening capability and high biocompatibility makes CPC a unique material for repairing bone defects. Near perfect adaptation of the cement to the tissue surfaces in a defect, and a gradual resorption followed by new bone formation are some of the other distinctive advantages of this biomaterial. In 1996 a CPC, consisting of tetracalcium phosphate and dicalcium phosphate anhydrous, was approved by the Food and Drug Administration (FDA) for repairing cranial defects in humans, thus becoming the first material of its kind available for clinical use. This paper will review the course of the development, the physical and chemical properties, and clinical applications of CPC.
Engineering Human Bone Grafts with New Macroporous Calcium Phosphate Cement Scaffolds
Journal of tissue engineering and regenerative medicine, 2017
Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps, and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering, and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from ...
ACS Biomaterials Science & Engineering, 2019
Finding alternative strategies for the regeneration of craniofacial bone defects (CSDs), such as combining a synthetic ephemeral calcium phosphate (CaP) implant and/or active substances and cells, would contribute to solving this reconstructive roadblock. However, CaP's architectural features (i.e., architecture and composition) still need to be tailored, and the use of processed stem cells and synthetic active substances (e.g., recombinant human bone morphogenetic protein 2) drastically limits the clinical application of such approaches. Focusing on solutions that are directly transposable to the clinical setting, biphasic calcium phosphate (BCP) and carbonated hydroxyapatite (CHA) 3D-printed disks with a triply periodic minimal structure (TPMS) were implanted in calvarial critical-sized defects (rat model) with or without addition of total bone marrow (TBM). Bone regeneration within the defect was evaluated, and the outcomes were compared to a standard-care procedure based on BCP granules soaked with TBM (positive control). After seven weeks, de novo bone formation was significantly greater in the CHA disks + TBM group than in the positive controls (3.33 and 2.15 mm 3 , respectively, P = 0.04). These encouraging results indicate that both CHA and TPMS architectures are potentially advantageous in the repair of CSDs and that this one-step procedure warrants further clinical investigation.
Calcium phosphate cements for bone engineering and their biological properties
Bone research, 2017
Calcium phosphate cements (CPCs) are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre-vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.
3D powder printed calcium phosphate implants for reconstruction of cranial and maxillofacial defects
2010
Background: The aim of this study was to investigate the processing and the possible use of 3D powder printed calcium phosphate implants for the reconstruction of cranial and maxillofacial defects. Materials: The fabrication of the implants was carried out with a commercial 3D powder printing system. Diluted phosphoric acid was printed onto tricalcium phosphate powder, leading to the formation of dicalcium phosphate dihydrate (Brushite). Hydrothermal conversion of the brushite matrices led to the formation of dicalcium phosphate anhydrous (Monetite). Method: Bony defects were generated using a human cadaver skull. The implants were computer-aided designed (CAD) using a mirror imaging procedure following computed tomography of the skull. Specific implants were manufactured by the 3D powder printing rapid prototyping technique. Result: The processing chain from data acquisition to printing of the implants proved to be practical and uncomplicated. The individual implants showed a high degree of accuracy of fit. Mechanical and physical investigations revealed suitable characteristics. Conclusion: 3D powder printing of calcium phosphate cement material provides a promising new method for the manufacturing of biodegradable synthetic patient-specific craniofacial implants. Ó 2010 European Association for Cranio-Maxillo-Facial Surgery Please cite this article in press as: Klammert U, et al. 3D powder printed calcium phosphate implants for reconstruction of cranial and maxillofacial defects, J Craniomaxillofac Surg (2010),
Use of a calcium phosphate matrix as a temporary cast for bony defect repair: a pilot study
Journal of Materials Science - J MATER SCI, 2003
The bony repair effect of different Calcium Phosphate Bone Cements was tested in a dog model. Seven different formulations were synthesized and tested on their biocompatibility, osseoconduction and biodegradability. Three dogs were used in this pilot study, in each dog 4 cranial, circular defects were made with a critical size diameter of 12 mm. Autologous bone was used as a control. The dogs were sacrificed after 6 months. Mineral phase analysis showed a reaction of the cements to form a more or less crystalline calciumhydroxyapatite. Histologic evaluation revealed that the presence of the cements stimulated the formation of a thin bone layer on the cranial and caudal side of each defect. The cements did not evoke an inflammatory reaction. Two formulations showed extensive bone formation.
Safety and efficacy of Chitra-CPC calcium phosphate cement as bone substitute
Calcium phosphate cements (CPCs) have gained importance in orthopaedics and dentistry as repair materials for bony/dentinal defects. They are aqueousbased, mouldable and osteoconductive materials which set into hydroxyapatite, the basic mineral of bone and teeth. A CPC product 'Chitra-CPC' has been developed. This communication compiles the safety and efficacy evaluation of Chitra-CPC. The evaluation plan consisted of acute systemic toxicity test (in mice for systemic response), intracutaneous reactivity test (in rabbits for skin response), pyrogen test (in rabbits for presence of pyrogens) and maximization sensitization test (in guinea pigs for allergic skin response). Soft tissue response was tested by implantation in rabbit paravertebral muscle, with histological evaluation at 1, 4 and 12 weeks post-implantation. The efficacy of the product to heal bone defects was investigated by implanting in rabbit femur with hydroxyapatite ceramic granules as the control. Local effects at macroscopic and microscopic levels were assessed at time periods of 4, 12, 26 and 52 weeks post implantation.
Premixed rapid-setting calcium phosphate composites for bone repair
Biomaterials, 2005
Although calcium phosphate cement (CPC) is promising for bone repair, its clinical use requires on site powder-liquid mixing. To shorten surgical time and improve graft properties, it is desirable to develop premixed CPC in which the paste remains stable during storage and hardens only after placement into the defect. The objective of this study was to develop premixed CPC with rapid setting when immersed in a physiological solution. Premixed CPCs were formulated using the following approach: Premixed CPC = CPC powder+nonaqueous liquid+gelling agent+hardening accelerator. Three premixed CPCs were developed: CPC-monocalcium phosphate monohydrate (MCPM), CPCchitosan, and CPC-tartaric. Setting time for these new premixed CPCs ranged from 5.3 to 7.9 min, significantly faster than 61.7 min for a premixed control CPC reported previously (p<05). SEM revealed the formation of nano-sized needle-like hydroxyapatite crystals after 1 d immersion and crystal growth after 7 d. Diametral tensile strength for premixed CPCs at 7 d ranged from 2.8 to 6.4 MPa, comparable to reported strengths for cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells attained a normal polygonal morphology on CPC-MCPM and CPCchitosan with cytoplasmic extensions adhering to the nano-hydroxyapatite crystals. In summary, fastsetting premixed CPCs were developed to avoid the powder-liquid mixing in surgery. The pastes hardened rapidly once immersed in physiological solution and formed hydroxyapatite. The cements had strengths matching those of cancellous bone and sintered porous hydroxyapatite and noncytotoxicity similar to conventional non-premixed CPC.
Bone regeneration by tuning the drug release from the calcium phosphate scaffolds
2017
Bone is among the most transplanted tissues for regeneration of bone defects, caused by trauma, age-related bone loss or bone infections. Due to their similar characteristics to the mineral phase of bone, calcium phosphates (CaPs) have raised a lot of interest. Some properties of CaPs, like biodegradability, biocompatibility, bioactivity and osteoconduction represent a great potential for this application. Among them, calcium phosphate cements (CPCs) have additional advantages like injectability and in situ hardening ability. Moreover, the possibility to tune the porosity of CaPs in general and of CPCs in particular, makes them suitable vehicles for local delivery of drugs. Loading CaPs with drugs allows conferring additional functionalities to the synthetic bone grafts, which is of great interest. The main aim of this thesis is to explore CaP bioceramics as vehicles for local delivery of drugs, covering both low temperature biomimetic ceramics, like calcium deficient hydroxyapatite...