Long‐term evaluation of the degradation behavior of three apatite‐forming calcium phosphate cements

Abstract

Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet™ . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue.

Multimodal porogen platforms for calcium phosphate cement degradation

“…PLGA particles disappear upon hydrolytic degradation, creating an acidic environment which accelerates the degradation of the CPC matrix, 8,34 increasing pore size compared to initial particle size. Regarding this discrepancy, the influence of particle size and manner of disappearance of both porogen platforms should be considered.…”

Sterilization effects on the handling and degradation properties of calcium phosphate cements containing poly (D,L‐lactic‐co‐glycolic acid) porogens and carboxymethyl cellulose

“…Moreover, CPCs do not exhibit many of the complications associated with auto‐ and allografts such as donor site morbidity and chronic pain, surgical harvesting, limited availability, and risk of disease transfer and/or infection . Nevertheless, the clinical applicability of CPCs has remained limited due to two factors: (i) poor degradability due to a lack of interconnected macroporosity to allow for vascularization and bone tissue ingrowth and (ii) poor cohesion and washout resistance, which is especially important when considering their indications for skeletal sites where perfusion is high, such as the spine . For the latter, extraosseous CPC leakage can lead to serious complications, as the release and subsequent washout of CPC particles into the blood stream can stimulate blood clotting and the formation of a pulmonary embolism that can lead to the death of the patient .…”

“…The ability of CMC to bind CPC particles together can also improve its injectability by eliminating or reducing a phenomenon known as filter pressing from occurring. Filter pressing often occurs when, during extrusion of the cement paste from a syringe, the liquid phase flows at a faster rate than the solid CPC particles, thus leaving behind a portion of the solid phase in the syringe . Consequently, CMC is an ideal binding agent and thickener to improve the clinical handling properties of CPCs.…”

“…The presence of macroporosity promotes fluid diffusion as well as cell migration which are beneficial to CPC resorption and new bone formation . To achieve this, CPCs were incorporated with poly ( D,L ‐lactic‐co‐glycolic acid) (PLGA) microparticles to act as porogens . PLGA is widely used in the biomedical sector as it is safe and biocompatible .…”

Antimicrobial hydroxyapatite–gelatin–silica composite pastes with tunable setting properties

“…However, the setting timescales of pure CP pastes often extend beyond the ideal therapeutic window that is minutes in range, especially for larger graft volumes 13 . At the same time, pure CP pastes set in relatively dense forms 14,15 , extending their resorption rate beyond the optimal range that is a few weeks in duration and offering no control over their porosity 16 , which is essential in enabling the bone substitute to mimic the extracellular matrix of bone and provide conditions for infiltration and proliferation of the host cells 17 , permeation of the blood plasma and vascularization, thus fostering the osseointegration process.…”