Degradation of calcium phosphate cements

Contains fulltext : 106967.pdf (publisher's version ) (Open Access)Calcium Phosphate Cements (CPC) are commonly used as bone replacement materials. Rosa Félix’s reseach specifically deals with strategies to enhance CPC degradation and its subsequent replacement by newly formed bone. In order to achieve this, several materials have been used in combination with CPC to create porosity that will increase fluid-flow and cell penetration throughout the implant material and therefore facilitate implant degradation. In this doctoral thesis research, the influence of several physico-chemical properties of varoius potential CPC porogens have been investigated in order to improve CPC degration and new bone formation. In addition, the influence of bio-active factors in this process of new bone formation has also been studied.Radboud Universiteit Nijmegen, 28 maart 2013Promotor : Jansen, J.A. Co-promotores : Wolke, J.G.C., Leeuwenburgh, S.C.G

In vitro degradation rate of apatitic calcium phosphate cement with incorporated PLGA microspheres

Item does not contain fulltextCalcium phosphate cements (CPCs) are frequently used as bone substitute material. Despite their superior clinical handling and excellent biocompatibility, they exhibit poor degradability, which limits bone ingrowth into the implant. Microspheres were prepared from poly(d,l-lactic-co-glycolic acid) (PLGA) and included in injectable CPCs as porogens in order to enhance its macroporosity after the polymeric microspheres had degraded. Upon degradation of the PLGA microspheres, acid is produced that enhances the dissolution rate of the CPC. However, the effect of the characteristics of PLGA microspheres on the degradation rate of CPCs has never been studied before. Therefore, the purpose of the current study was to investigate the dependence of CPC degradation on the chemical and morphological characteristics of incorporated PLGA microspheres. With respect to the chemical characteristics of the PLGA microspheres, the effects of both PLGA molecular weight (5, 17 and 44kDa) and end-group functionalization (acid-terminated or end-capped) were studied. In addition, two types of PLGA microspheres, differing in morphology (hollow vs. dense), were tested. The results revealed that, although both chemical parameters clearly affected the polymer degradation rate when embedded as hollow microspheres in CPC, the PLGA and CPC degradation rates were mainly dependent on the end-group functionalization. Moreover, it was concluded that dense microspheres were more efficient porogens than hollow ones by increasing the CPC macroporosity during in vitro incubation. By combining all test parameters, it was concluded that dense PLGA microspheres consisting of acid-terminated PLGA of 17kDa exhibited the highest and fastest acid-producing capacity and correspondingly the highest and fastest amount of porosity. In conclusion, the data presented here indicate that the combination of dense, acid-terminated PLGA microspheres with CPC emerges as a successful combination to achieve enhanced apatitic CPC degradation

New polyoxazoline loaded patches for hemostasis in experimental liver resection

A new cost-effective NHS functionalized polyoxazoline (POx) loaded polymer with strong hemostatic properties has been developed. In this study, we investigate POx loaded hemostatic patches regarding hemostatic efficacy, local inflammatory reaction and wound-healing, as compared to the non-POx treated blanks and commercially available hemostatic products. Hundred and ten rats divided into 11 groups of 10 animals underwent partial liver lobe resection. Eight groups received experimental patches, two groups commercially available hemostatic patches (TachoSil® and Veriset™, positive controls), one group with gauzes (negative control). Each animal received twice a patch with a size 1.5 × 2.5 cm, on each partially resected lobe. Primary endpoint was time to hemostasis (TTH). The rats were sacrificed at different time points (1, 3, or 7 days) to measure local inflammatory response and early wound healing. Of the POx loaded patches, GFC NHS-POx (TTH 20.4 s, p = .019) and GFC-NHS-POx1.5 (TTH 0.0 s, p = .003) showed significantly faster TTH compared to TachoSil® (TTH 95.4 s), and were comparable to Veriset™ (TTH 17.0 s). Three patches, GFC-NHS-POx 1.5 (TTH 0.0 s, p = .016), ORC NHS-POx:NU-POx (TTH 91.4 s, p = .033), and ORC-PLGA NHS-POx:NU-POx (TTH 105.6 s, p = .04) had a lower TTH compared to their own blank carrier (TTH 74.9, 157.8, and 195.7 s, respectively). With regard to biocompatibility, all POx loaded patches showed results comparable to TachoSil® and Veriset™. NHS-POx-loaded hemostatic patch demonstrate fast and effective hemostasis, comparable or better than commercially available hemostatic patches, with similar early biocompatibility

Three different strategies to obtain porous calcium phosphate cements: comparison of performance in a rat skull bone augmentation model.

Item does not contain fulltextPreprosthetic surgery has become a routine procedure to obtain sufficient bone quantity and quality for dental implant installation in patients with an initial inadequate bone volume. Although autologous bone onlay or inlay grafting is still the preferred bone augmentation technique, a broad range of synthetic bone substitutes have been developed, for example, calcium phosphate cement (CPC). The introduction of porosity within CPC can be used to increase CPC degradation and bone ingrowth. Therefore, three different strategies to obtain porous CPCs were evaluated in this preclinical study. Instantaneously porous CPC (CPC-IP) was compared with delayed porous CPC in vitro and in vivo. CPC-IP was obtained by the creation of CO(2) bubbles during setting, whereas delayed porous CPC was obtained after the degradation of incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres. As an additional aspect, delayed porous CPC was created by the incorporation of either hollow or dense degradable PLGA microspheres (CPC-hPLGA and CPC-dPLGA). All CPC compositions showed appropriate clinical handling properties and an interconnected porous structure with a final porosity above 70% (v/v). In vitro degradation studies showed the gradual formation of pores and further CPC-matrix dissolution for CPCs containing PLGA microspheres (dPLGA microspheres > hPLGA microspheres). For in vivo evaluation of the CPCs, an augmentation model was used, allowing a CPC injection into a rigidly immobilized Teflon ring on the rat skull. Histological evaluation after 12 weeks of implantation showed bone formation using all three CPCs. Bone apposition reached volumetric amounts of up to 10% of the augmentation area and a maximum augmentation height of approximately 1 mm. CPC-IP showed significantly more bone formation and resulted in a superior bone apposition height compared with both CPCs containing PLGA microspheres. No differences in biological performance were observed between the CPCs containing hPLGA and those containing dPLGA microspheres. Further research is necessary to enhance the bone appositional speed and amount of CPCs for bone augmentation procedures before them being used in a potential clinical setting.1 juni 201

A systematic review and meta-analyses on animal models used in bone adhesive research

Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An overview in this field is missing. This systematic review highlights the relevant parameters for design of experimental bone adhesive studies. It demonstrates evidence regarding benefit of bone adhesives but also that the quality of reporting and the risk of bias in studies need to be improved. The results will aid in designing better quality animal studies for bone adhesive research with higher translational value

Influence of the pore generator on the evolution of the mechanical properties and the porosity and interconnectivity of a calcium phosphate cement.

Item does not contain fulltextPorosity and interconnectivity are important properties of calcium phosphate cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved by adding polymeric biodegradable pore-generating particles (porogens), which can add porosity to the CPC and can also be used as a drug-delivery system. Porosity affects the mechanical properties of CPCs, and hence is of relevance for clinical application of these cements. The current study focused on the effect of combinations of polymeric mesoporous porogens on the properties of a CPC, such as specific surface area, porosity and interconnectivity and the development of mechanical properties. CPC powder was mixed with different amounts of PLGA porogens of various molecular weights and porogen sizes. The major factors affecting the properties of the CPC were related to the amount of porogen loaded and the porogen size; the molecular weight did not show a significant effect per se. A minimal porogen size of 40 mum in 30 wt.% seems to produce a CPC with mechanical properties, porosity and interconnectivity suitable for clinical applications. The properties studied here, and induced by the porogen and CPC, can be used as a guide to evoke a specific host-response to maintain CPC integrity and to generate an explicit bone ingrowth.1 januari 201