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Premixed rapid-setting calcium phosphate composites for bone repair.
Lisa E Carey1, Hockin H K Xu, Carl G Simon
1American Dental Association Foundation, Paffenbarger Research Center, National Institute of Standards and Technology, 100 Bureau Drive Stop 8546, Gaithersburg, MD 20899-8546, USA.
This study aimed to develop a new type of calcium phosphate cement (CPC) that eliminates the need for on-site mixing during surgery. Traditional CPC requires surgeons to mix powder and liquid components at the operating site, which can be time-consuming and increase the risk of contamination. The researchers created three new premixed CPC formulations that remain stable during storage and harden rapidly when placed in a physiological solution. The new CPCs set in 5.3 to 7.9 minutes, much faster than the 61.7 minutes required for a previously reported control CPC. After setting, the CPCs formed nano-sized hydroxyapatite crystals, which are important for bone repair. The materials also showed mechanical strength comparable to cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells adhered to the CPC surfaces, indicating biocompatibility. The new formulations could improve clinical efficiency by reducing surgical time and handling complexity.
Area of Science:
- Biomedical materials science
- Orthopedic surgery
- Calcium phosphate cement research
Background:
Calcium phosphate cement (CPC) is widely recognized for its potential in bone repair applications. However, its clinical use typically involves on-site mixing of powder and liquid components, which can prolong surgical procedures. Prior research has shown that this step increases the risk of contamination and complicates handling during surgery. While CPC offers biocompatibility and osteoconductivity, the need for in-situ mixing limits its adoption. No prior work had resolved the challenge of developing a premixed CPC that remains stable during storage and hardens only after placement. This gap motivated the exploration of new formulations that eliminate the mixing step. The uncertainty around how to achieve rapid setting while maintaining structural integrity remains unresolved. This study aimed to address these limitations by designing a premixed CPC that hardens quickly upon contact with physiological fluids.
Purpose Of The Study:
The primary aim of this study was to develop a premixed calcium phosphate cement that eliminates the need for on-site powder-liquid mixing during surgery. The researchers focused on creating a formulation that remains stable during storage and hardens rapidly when immersed in a physiological solution. The motivation stemmed from the desire to reduce surgical time and improve handling of the graft material. By avoiding the mixing step, the new CPC could enhance clinical efficiency and reduce procedural variability. The study also aimed to evaluate the mechanical properties and biocompatibility of the new CPC formulations. The researchers hypothesized that a combination of a nonaqueous liquid, gelling agent, and hardening accelerator could achieve the desired rapid setting. The objective was to compare the performance of three new CPC formulations against a previously reported control. The ultimate goal was to develop a clinically viable CPC with properties suitable for bone repair.
Main Methods:
The researchers developed three new premixed CPC formulations using a specific approach. Each formulation combined CPC powder with a nonaqueous liquid, a gelling agent, and a hardening accelerator. The three formulations tested were CPC-monocalcium phosphate monohydrate (MCPM), CPC-chitosan, and CPC-tartaric. The setting time of each CPC was measured after immersion in a physiological solution. Scanning electron microscopy (SEM) was used to assess the formation of hydroxyapatite crystals after 1 and 7 days of immersion. Diametral tensile strength was evaluated at 7 days to compare with cancellous bone and sintered porous hydroxyapatite. Osteoblast cell morphology was analyzed on the CPC surfaces to assess biocompatibility. The study compared the new CPCs with a previously reported control CPC. The researchers used statistical analysis to determine the significance of differences in setting times. The methods focused on evaluating both mechanical and biological properties of the new CPC formulations.
Main Results:
The three new premixed CPCs had significantly shorter setting times compared to the control CPC. Setting times ranged from 5.3 to 7.9 minutes, versus 61.7 minutes for the control (p < 0.05). Scanning electron microscopy showed the formation of nano-sized needle-like hydroxyapatite crystals after 1 day of immersion. By 7 days, these crystals had grown in size and structure. Diametral tensile strength at 7 days ranged from 2.8 to 6.4 MPa, which is comparable to cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells exhibited normal polygonal morphology on CPC-MCPM and CPC-chitosan surfaces. The cells extended cytoplasmic projections that adhered to the hydroxyapatite crystals. The new CPCs demonstrated non-cytotoxic properties similar to conventional non-premixed CPC. These findings suggest that the new formulations meet the mechanical and biological requirements for bone repair applications.
Conclusions:
The study successfully developed three fast-setting premixed CPCs that eliminate the need for on-site powder-liquid mixing. The new formulations hardened rapidly when immersed in a physiological solution, forming hydroxyapatite crystals. The mechanical strength of the CPCs matched that of cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells showed normal morphology and adhesion on the CPC surfaces, indicating biocompatibility. The results suggest that the new CPCs could improve clinical efficiency by reducing surgical time and handling complexity. The findings align with the authors' stated goal of developing a premixed CPC suitable for bone repair. The study supports the claim that the new CPCs have properties comparable to conventional CPCs. The authors propose that these formulations could be viable alternatives in clinical settings.
Frequently Asked Questions
The main advantage is the elimination of on-site powder-liquid mixing, reducing surgical time and simplifying handling.
They harden rapidly when immersed in a physiological solution, forming hydroxyapatite crystals within minutes.
To maintain paste stability during storage and trigger hardening only after placement in a physiological environment.
Hydroxyapatite forms after setting and provides structural strength and biocompatibility for bone repair.
It ranged from 2.8 to 6.4 MPa at 7 days, comparable to cancellous bone and sintered porous hydroxyapatite.
Yes, osteoblasts exhibited normal morphology and adhered to the hydroxyapatite crystals on CPC surfaces.