In this study, we evaluate a new bioadhesive for intra-abdominal onlay mesh fixation of a polypropylene–polyvinylchloride graft.

Bone substitute material properties such as granule size, macroporosity, microporosity and shape have been shown to influence the cellular inflammatory response to a bone substitute material. Keeping these parameters constant, the present study analyzed the in vivo tissue reaction to three bone substitute materials (granules) with different chemical compositions (hydroxyapatite (HA), beta-tricalcium phosphate (TCP) and a mixture of both with a HA/TCP ratio of 60/40 wt%). Using a subcutaneous implantation model in Wistar rats for up to 30 days, tissue reactions, including the induction of multinucleated giant cells and the extent of implantation bed vascularization, were assessed using histological and histomorphometrical analyses. The results showed that the chemical composition of the bone substitute material significantly influenced the cellular response. When compared to HA, TCP attracted significantly greater multinucleated giant cell formations within the implantation bed. Furthermore, the vascularization of the implantation bed of TCP was significantly higher than that of HA implantation beds. The biphasic bone substitute group combined the properties of both groups. Within the first 15 days, high giant cell formation and vascularization rates were observed, which were comparable to the TCP-group. However, after 15 days, the tissue reaction, i.e. the extent of multinucleated giant cell formation and vascularization, was comparable to the HA-group. In conclusion, the combination of both compounds HA and TCP may be a useful combination for generating a scaffold for rapid vascularization and integration during the early time points after implantation and for setting up a relatively slow degradation. Both of these factors are necessary for successful bone tissue regeneration.

Tissue engineering is an attractive approach to heal bony defects. However, three-dimensional cell-scaffold constructs display uneven oxygen supply resulting in inhomogeneous tissue quality. We assessed different strategies to improve oxygen supply in vitro. Scaffolds with differing inner surface were seeded with preosteoblastic cells and cultivated either statically or in perfusion bioreactors. Oxygen concentration and pH were measured in the center of the scaffolds. An inductive feedback mechanism was build to increase bioreactor pump speed according to the oxygen concentrations measured within the scaffolds. While pH remained stable, oxygen concentration decreased significantly under static conditions within the cell-seeded scaffolds. Reducing the scaffolds' inner surface as well as increasing perfusion speeds in bioreactors resulted in improved oxygen supply. We conclude that improving oxygen supply to three dimensional culture systems for bone tissue engineering is feasible in an automated manner. Culture conditions have to be adapted to each cell-scaffold system individually.

Various biomaterials have been developed for the use as bone substitutes for bone defects. To optimize their integration and functionality, they should be adapted to the individual defect. Rapid prototyping is a manufacturing method to tailor materials to the 3D geometry of the defect. Especially 3D printing allows the manufacture of implants, the shape of which can be designed to fit the bone defect using anatomical information obtained from the patient. 3D printing of calcium phosphates, which are well established as bone substitutes, involves a sintering step after gluing the granules together by a binder liquid. In this study, we analyzed if and how these 3D printed calcium phosphate surfaces can be resorbed by osteoclast-like cells. On 3D printed scaffold surfaces consisting of pure HA and β-TCP as well as a biphasic mixture of HA and TCP the osteoclastic cell differentiation was studied. In this regard, cell proliferation, differentiation, and activation were analyzed with the monocytic cell line RAW 264.7. The results show that osteoclast-like cells were able to resorb calcium phosphate surfaces consisting of granules. Furthermore, biphasic calcium phosphate ceramics exhibit, because of their osteoclastic activation ability, the most promising surface properties to serve as 3D printed bone substitute scaffolds.

Aim: The aim of the study was to evaluate the impact of BMP on the resorption and degradation of a calcium phosphate ceramic.

The chemical composition of calcium phosphate (CaP) materials for the regenerative therapy of large bone defects is similar to that of bone. Additionally, calcium phosphates show an excellent biocompatibility. Besides the support of defect healing calcium phosphate implants should be completely degraded within an adequate time period to be replaced by newly formed bone. Although degradation of CaP‐implants occurs mainly by dissolution of the material, it is important to characterize the osteoclastic resorption as well, which is involved in native bone remodeling. The degradation of bone substitutes made of calcium phosphate ceramics is influenced by various parameters, such as defect size and localization, the general health situation, and age of the patient, but also material properties are important. Especially, the calcium phosphate composition is crucial for the degradation behavior of a calcium phosphate material. Additionally, at the cellular level the micro‐ and macroporosity, including interconnecting pores, influences both, the dissolution and the osteoclastic resorption. In our study, three different calcium phosphate materials (hydroxyapatite, tricalcium phosphate, and a biphasic calcium phosphate) and two different geometries (dense 2D samples and porous 3D scaffolds) are compared regarding their dissolution and resorption behavior. The results show, that the dissolution of CaP‐ceramics, as examined by the incubation in a degradation solution, depends mainly on the calcium phosphate phase but also on the porosity of the implant. Regarding the resorption, cell proliferation and differentiation of a monocytic cell line as well as the formation of resorption lacunas are analyzed. Cell proliferation is comparable on all phase compositions. Cell differentiation and resorption, however, are influenced by the calcium phosphate phase composition and by the implant porosity as well. By understanding these two mechanisms of degradation, bone substitute materials and, as a result, the bone regeneration of large bone defects using CaP‐ceramics can be improved.

While various materials have been developed for bone substitute and bone tissue engineering applications over the last decades, processing techniques meeting the high demands of scaffold shaping are still under development. Individually adapted and mechanically optimised scaffolds can be derived from calcium phosphate (CaP-) ceramics via rapid prototyping (RP). In this study, porous ceramic scaffolds with a periodic pattern of interconnecting pores were prepared from hydroxyapatite, β-tricalcium phosphate and biphasic calcium phosphates using a negative-mould RP technique. Moulds predetermining various pore patterns (round and square cross section, perpendicular and 60° inclined orientation) were manufactured via a wax printer and subsequently impregnated with CaP-ceramic slurries. Different pore patterns resulted in macroporosity values ranging from about 26.0–71.9 vol% with pore diameters of approximately 340 μm. Compressive strength of the specimens (1.3–27.6 MPa) was found to be mainly influenced by the phase composition as well as the macroporosity, both exceeding the influence of the pore geometry. A maximum was found for scaffolds with 60 wt% hydroxyapatite and 26.0 vol% open porosity. It has been shown that wax ink-jet printing allows to process CaP-ceramic into scaffolds with highly defined geometry, exhibiting strength values that can be adjusted by phase composition and pore geometry. This strength level is within and above the range of human cancellous bone. Therefore, this technique is well suited to manufacture scaffolds for bone tissue engineering.

The adequate regeneration of large bone defects is still a major problem in orthopaedic surgery. Synthetic bone substitute materials have to be biocompatible, biodegradable, osteoconductive and processable into macroporous scaffolds tailored to the patient specific defect. Hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as mixtures of both phases, biphasic calcium phosphate ceramics (BCP), meet all these requirements and are considered to be optimal synthetic bone substitute materials. Rapid prototyping (RP) can be applied to manufacture scaffolds, meeting the criteria required to ensure bone ingrowth such as high porosity and defined pore characteristics. Such scaffolds can be used for bone tissue engineering (BTE), a concept based on the cultivation of osteogenic cells on osteoconductive scaffolds. In this study, scaffolds with interconnecting macroporosity were manufactured from HA, TCP and BCP (60 wt% HA) using an indirect rapid prototyping technique involving wax ink-jet printing. ST-2 bone marrow stromal cells (BMSCs) were seeded onto the scaffolds and cultivated for 17 days under either static or dynamic culture conditions and osteogenic stimulation. While cell number within the scaffold pore system decreased in case of static conditions, dynamic cultivation allowed homogeneous cell growth even within deep pores of large (1,440 mm(3)) scaffolds. Osteogenic cell differentiation was most advanced on BCP scaffolds in both culture systems, while cells cultured under perfusion conditions were generally more differentiated after 17 days. Therefore, scaffolds manufactured from BCP ceramic and seeded with BMSCs using a dynamic culture system are the method of choice for bone tissue engineering.

Die Erfindung betrifft einen Werkstoff fur den uberwiegend medizinischen, langfristigen in vivo Einsatz, wie bspw. als Fullungswerkstoff in der Zahnmedizin. The invention relates to a material for the predominantly medical, long-term in vivo use, such as, as a filling material in dentistry. Die Aufgabe der Erfindung, einen Werkstoff fur uberwiegend medizinischen, langfristigen in vivo Einsatz anzugeben, der die Nachteile des Standes der Technik vermeidet und ohne ein Wirkstoff-Releasing initiiert wird sowie nach dem Abtragen des Materials oder trotz Veranderung der Werkstoffform weiterhin bestehen bleibt, wird dadurch gelost, dass der Werkstoff aus Polymeren und Fullkorpern besteht, wobei die Fullkorper mit einem Polymer beschichtete, chemisch modifizierte, Hydroxylgruppen-tragende Partikel sind, die von einer Matrix eines weiteren Polymers umgeben sind, wobei das beschichtende Polymer antimikrobielle Wirkung entfaltet. The object of the invention to provide a material for mainly medical, long-term in vivo use, which avoids the disadvantages of the prior art and is initiated without a drug-releasing well as after removal of the material or in spite of change in the material form persists, thereby achieved in that the material consists of polymers and filler, wherein the filler coated with a polymer, chemically modified, hydroxyl-bearing particles, which are surrounded by a matrix of another polymer, said coating polymer develops anti-microbial activity.

Nanocrystalline calcium phosphates containing carbonate have a high similarity to bone mineral. The reactions of bone cells (primary osteoblasts and osteoclast-like cells) on these materials as well as on sintered β-tricalcium phosphate and hydroxyapatite (HA) confirmed a good biocompatibility of the nanocrystalline samples. However, osteoclastic differentiation was constrained on the carbonate-rich samples, leading to a small number of osteoclast-like cells on the materials and few resorption pits. The grain size of the calcium phosphate ceramics (nano vs. micro) was less important than expected from to physico-chemical considerations. When comparing the nanocrystalline samples, the highest resorption rate was found for nano-HA with a low carbonate content, which strongly stimulated the differentiation of osteoclast-like cells on its surface.

Hydroxyapatite (HA) ceramic is a widely used synthetic bone substitute material for the regeneration of bone defects. We manufactured HA scaffolds with adjustable pore sizes and pore geometry by dispense-plotting. In addition, we attached peptides covalently onto the HA surface and are able to simultaneously quantify the amount of covalently attached and adsorbed peptide down to the picomolar range with a novel fluorescence-based detection method. In cell culture assays with stromal bone marrow cells, we observed a positive effect of biofunctionalization on cell differentiation after 21 days of culture when comparing the scaffold functionalized with the RGD motif containing adhesion peptide to an unmodified scaffold.

Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff’s base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.

In vitro-Abbauuntersuchungen an Makroporösen 3D-Scaffolds auf Calciumphosphatbasis S. Schlüfter, S. Schlüfter Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, DeutschlandSearch for more papers by this authorR. Detsch, R. Detsch BioCer Entwicklungs-GmbH, Bayreuth, DeutschlandSearch for more papers by this authorU. Deisinger, U. Deisinger Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, DeutschlandSearch for more papers by this authorG. Ziegler, G. Ziegler Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, Deutschland BioCer Entwicklungs-GmbH, Bayreuth, DeutschlandSearch for more papers by this author S. Schlüfter, S. Schlüfter Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, DeutschlandSearch for more papers by this authorR. Detsch, R. Detsch BioCer Entwicklungs-GmbH, Bayreuth, DeutschlandSearch for more papers by this authorU. Deisinger, U. Deisinger Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, DeutschlandSearch for more papers by this authorG. Ziegler, G. Ziegler Friedrich-Baur-Forschungsinstitut für Biomaterialien, Universität Bayreuth, Deutschland BioCer Entwicklungs-GmbH, Bayreuth, DeutschlandSearch for more papers by this author Book Editor(s):Prof. Dr.-Ing. Walter Krenkel, Prof. Dr.-Ing. Walter Krenkel Lehrstuhl Keram. Werkstoffe, Universität Bayreuth, Ludwig-Thoma-Str. 36b, 95440 Bayreuth, DeutschlandSearch for more papers by this author First published: 15 April 2009 https://doi.org/10.1002/9783527627110.ch99 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Summary Für die Untersuchung des Abbauverhaltens von porösen, synthetischen Calciumphosphaten wurden Degradations- und Resorptionsuntersuchungen an makroporösen 3D-Scaffolds aus HA, TCP und HA/TCP 60/40 Gew.-% durchgeführt. Die Ergebnisse dieser in vitro-Abbauuntersuchungen zeigen eine deutliche Abhängigkeit des Abbauverhaltens von der verwendeten CaP Phase. Aufgrund der Ergebnisse kann das poröse 3D-Scaffold mit der Phasenzusammensetzung HA/TCP 60/40 als ideales Knochenersatzmaterial angesehen werden. Verbundwerkstoffe: 17. Symposium Verbundwerkstoffe und Werkstoffverbunde RelatedInformation

Chitosan crosslinked with glutaraldehyde or oxidised dextran was studied as a potential scaffold material in tissue engineering for cartilage regeneration. By mixing two solutions of both components it became a gel, which was frozen. After lyophilisation a scaffold was generated with interconnected pores with diameters ranging between 120–350 μm. The mechanical properties (yielding point, elastic and viscous moduli), absolute porosity, pore morphology were determined depending on the ratio of chitosan to crosslinker. ATDC5 (murine cell line) and bovine articular chondrocytes (primary cells) were cultured for 14 days on the scaffolds. Cultivation with ATDC5 cells and bovine chondrocytes showed no negative influence of glutaraldehyde on cell vitality and growth.

The 3-D printing technique was used for the fabrication of HA, TCP and BCP ceramics and the influence of the granulate composition on the 3-D printed scaffolds was investigated. An optimal composition for 3-D printing granulates was found. Thus, individual implants can be manufactured via 3-D printing from different CaP phase compositions to tailor their degradation behavior and osteoconductivity for enhanced bone healing.