RSA migration of unicondylar knee arthroplasties is comparable to migration of total knee arthroplasties: A meta-analysis.

IMPORTANCE: Aseptic loosening is a major cause of failure for unicondylar knee arthroplasty (UKA). In total knee arthroplasty (TKA), early migration as measured with radiostereometric analysis (RSA) is a strong predictor of late revision for aseptic loosening of the tibial component. Migration in the first two years provides information on the fixation of an implant. However, the migration pattern of UKAs has not been systematically determined, and it is unclear if the migration pattern of UKAs is similar to that of TKAs. Therefore, the present meta-analysis aims to evaluate the migration patterns of tibial components of UKAs. EVIDENCE REVIEW: All RSA studies reporting on migration at two or more postoperative time-points following UKA were included. Pubmed, Web of Science, Cochrane, and Embase were searched up to April 2021. The risk of bias was assessed using the methodological score of the Assessment of Quality in Lower Limb Arthroplasty tool. All phases of the review were performed by two reviewers independently. A random-effects model was applied to pool the migration data. FINDINGS: The literature search yielded 3,187 hits, of which ten studies were included, comprising 13 study groups and 381 UKAs. The majority of the early migration occurred in the first 6 months postoperatively followed by a period of very little migration, similar to what is reported for TKAs. The pooled mean migration expressed as the maximum total point motion of all UKAs at 3 months, 6 months, 1 year, and 2 years was 0.43 mm (95% CI 0.38-0.48), 0.54 mm (95% CI 0.40-0.67), 0.59 mm (95% CI 0.52-0.66), and 0.61 mm (95% CI 0.55-0.68), respectively. Migration at one year and two years was higher than migration of TKAs as reported in previous studies. All-polyethylene UKAs migrated more at one year (0.69 mm; 95% CI 0.58-0.80) than metal-backed UKAs (0.52 mm; 95% CI 0.46-0.58). CONCLUSIONS AND RELEVANCE: The migration pattern of UKAs is comparable with that of TKAs in the first two years as both types of implants show initial migration in the first few months and very little migration thereafter. However, UKAs had higher migration at 1-year and 2-year follow-up.

Integrity of the hip capsule measured with magnetic resonance imaging after capsular repair or unrepaired capsulotomy in hip arthroscopy.

BACKGROUND: Current literature shows no clear answer on the question how to manage the capsule after hip arthroscopy. Regarding patient reported outcome measures there seems to be no difference between capsular repair or unrepaired capsulotomy. AIM: To evaluate and compare the integrity of the hip capsule measured on a magnetic resonance imaging (MRI) scan after capsular repair or unrepaired capsulotomy. METHODS: A case series study was performed; a random sample of patients included in a trial comparing capsular repair vs unrepaired capsulotomy had a postoperative MRI scan. The presence of a capsular defect and gap size were independently evaluated on MRI. RESULTS: A total of 28 patients (29 hips) were included. Patient demographics were comparable between treatment groups. There were 2 capsular defects in the capsular repair group and 7 capsular defects in the unrepaired capsulotomy group (P = 0.13). In the group of patients with a defect, median gap sizes at the acetabular side were 5.9 mm (range: 2.7-9.0) in the repaired and 8.0 mm (range: 4.5-18.0) in the unrepaired group (P = 0.462). At the muscular side gap sizes were 6.6 mm (range: 4.1-9.0) in the repaired group and 11.5 mm (range: 3.0-18.0) in the unrepaired group (P = 0.857). The calculated Odds ratio (OR) for having a capsular defect with an increasing lateral center-edge (CE) angle was 1.12 (P = 0.06). The OR for having a capsular defect is lower in the group of patients that underwent a labral repair with an OR of 0.1 (P = 0.05). CONCLUSION: There is no significant difference in capsular defects between capsular repair or unrepaired capsulotomy. Regarding clinical characteristics our case series shows that a larger CE angle increases the likelihood of a capsular defect and the presence of a labral repair decreases the likelihood of a capsular defect.

Decision aids can decrease decisional conflict in patients with hip or knee osteoarthritis: Randomized controlled trial.

BACKGROUND: The interest in shared decision making has increased considerably over the last couple of decades. Decision aids (DAs) can help in shared decision making. Especially when there is more than one reasonable option and outcomes between treatments are comparable. AIM: To investigate if the use of DAs decreases decisional conflict in patients when choosing treatment for knee or hip osteoarthritis (OA). METHODS: In this multi-center unblinded randomized controlled trial of patients with knee or hip OA were included from four secondary and tertiary referral centers. One-hundred-thirty-one patients who consulted an orthopedic surgeon for the first time with knee or hip OA were included between December 2014 and January 2016. After the first consultation, patients were randomly assigned by a computer to the control group which was treated according to standard care, or to the intervention group which was treated with standard care and provided with a DA. After the first consultation, patients were asked to complete questionnaires about decisional conflict (DCS), satisfaction, anxiety (PASS-20), gained knowledge, stage of decision making and preferred treatment. Follow-up was carried out after 26 wk and evaluated decisional conflict, satisfaction, anxiety, health outcomes (HOOS/KOOS), quality of life (EQ5D) and chosen treatment. RESULTS: After the first consultation, patients in the intervention group (mean DCS: 25 out of 100, SD: 13) had significantly (P value: 0.00) less decisional conflict compared to patients in the control group (mean DCS: 39 out of 100, SD 11). The mean satisfaction score for the given information (7.6 out of 10, SD: 1.8 vs 8.6 out of 10, SD: 1.1) (P value: 0.00), mean satisfaction score with the physician (8.3 out of 10, SD: 1.7 vs 8.9 out of 10, SD: 0.9) (P value: 0.01) and the mean knowledge score (3.3 out of 4, SD: 0.9 vs 3.7 out of, SD: 0.6) (P value: 0.01) were all significantly higher in the intervention group. At 26-wk follow-up, only 75 of 131 patients (57%) were available for analysis. This sample is too small for meaningful analysis. CONCLUSION: Providing patients with an additional DA may have a positive effect on decisional conflict after the first consultation. Due to loss to follow-up we are unsure if this effect remains over time.

Methylcellulose - a versatile printing material that enables biofabrication of tissue equivalents with high shape fidelity.

With the aid of biofabrication, cells can be spatially arranged in three dimensions, which offers the opportunity to guide tissue maturation in a better way compared to traditional tissue engineering approaches. A prominent technique allowing biofabrication of tissue equivalents is extrusion-based 3D (bio)printing, also called 3D (bio)plotting or robocasting, which comprises cells embedded in the biomaterial (bioink) during the fabrication process. First bioprinting studies introduced bioinks allowing either good cell viability or good shape fidelity. Concepts enabling printing of cell-laden constructs with high shape fidelity were developed only rarely. Recent studies showed the great potential of the polysaccharide methylcellulose (mc) as supportive biomaterial that can be utilized in various ways to enable biofabrication and especially extrusion-based bioprinting of bioinks. This minireview highlights the multiple applications of mc for biofabrication: it was successfully used as sacrificial ink to enable 3D shaping of cell sheets or biomaterial inks as well as as internal stabilizing component of various bioinks. Moreover, a brief overview about first bioprinted functional tissue equivalents is given, which have been fabricated by using mc. Based on these studies, future research should consider mc as an auxiliary material for bioinks and biofabricated constructs with high shape fidelity.

Sorting Fermionization from Crystallization in Many-Boson Wavefunctions.

Fermionization is what happens to the state of strongly interacting repulsive bosons interacting with contact interactions in one spatial dimension. Crystallization is what happens for sufficiently strongly interacting repulsive bosons with dipolar interactions in one spatial dimension. Crystallization and fermionization resemble each other: in both cases - due to their repulsion - the bosons try to minimize their spatial overlap. We trace these two hallmark phases of strongly correlated one-dimensional bosonic systems by exploring their ground state properties using the one- and two-body density matrix. We solve the N-body Schrödinger equation accurately and from first principles using the multiconfigurational time-dependent Hartree for bosons (MCTDHB) and for fermions (MCTDHF) methods. Using the one- and two-body density, fermionization can be distinguished from crystallization in position space. For N interacting bosons, a splitting into an N-fold pattern in the one-body and two-body density is a unique feature of both, fermionization and crystallization. We demonstrate that this splitting is incomplete for fermionized bosons and restricted by the confinement potential. This incomplete splitting is a consequence of the convergence of the energy in the limit of infinite repulsion and is in agreement with complementary results that we obtain for fermions using MCTDHF. For crystalline bosons, in contrast, the splitting is complete: the interaction energy is capable of overcoming the confinement potential. Our results suggest that the spreading of the density as a function of the dipolar interaction strength diverges as a power law. We describe how to distinguish fermionization from crystallization experimentally from measurements of the one- and two-body density.

Strontium-modified premixed calcium phosphate cements for the therapy of osteoporotic bone defects.

In this study a premixed strontium-containing calcium phosphate bone cement for the application in osteoporotic bone defects has been developed and characterised regarding its material and in vitro properties as well as minimally invasive applicability in balloon kyphoplasty. Strontium was introduced into the cement by substitution of one precursor component, CaCO3, with its strontium analogue, SrCO3. Using a biocompatible oil phase as carrier liquid, a cement paste that only set upon contact with aqueous environment was obtained. Strontium modification resulted in an increased strength of set cements and radiographic contrast; and the cements released biologically relevant doses of Sr2+-ions that were shown to enhance osteoprogenitor cell proliferation and osteogenic differentiation. Finally, applicability of strontium-containing cement pastes in balloon kyphoplasty was demonstrated in a human cadaver spine procedure. The cement developed in this study may therefore be well suited for minimally invasive, osteoporosis-related bone defect treatment. STATEMENT OF SIGNIFICANCE: Strontium-releasing calcium phosphate bone cements are promising materials for the clinical regeneration of osteoporosis-related bone defects since they have been shown to stimulate bone formation and at the same time limit osteoclastic bone resorption. Today clinical practice favours minimally invasive surgical techniques, e.g. for vertebral fracture treatment, posing special demands on such cements. We have therefore developed a premixed, strontium-releasing bone cement with enhanced mechanical properties and high radiographic visibility that releases biologically relevant strontium concentrations and thus stimulates cells of the osteogenic lineage. In a pilot experiment we also exemplify its excellent suitability for minimally invasive balloon kyphoplasty procedures.

Development of a clay based bioink for 3D cell printing for skeletal application.

Three-dimensional printing of cell-laden hydrogels has evolved as a promising approach on the route to patient-specific or complex tissue-engineered constructs. However, it is still challenging to print structures with both, high shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay, called Laponite, to build up scaffolds utilising the extrusion-based method 3D plotting. By blending with alginate and methylcellulose, a bioink was developed which allowed easy extrusion, achieving scaffolds with high printing fidelity. Following extrusion, approximately 70%-75% of printed immortalised human mesenchymal stem cells survived and cell viability was maintained over 21 days within the plotted constructs. Mechanical properties of scaffolds comprised of the composite bioink decreased over time when stored under cell culture conditions. Nevertheless, shape of the plotted constructs was preserved even over longer cultivation periods. Laponite is known for its favourable drug delivery properties. Two model proteins, bovine serum albumin and vascular endothelial growth factor were loaded into the bioink. We demonstrate that the release of both growth factors significantly changed to a more sustained profile by inclusion of Laponite in comparison to an alginate-methylcellulose blend in the absence of Laponite. In summary, addition of a synthetic clay, Laponite, improved printability, increased shape fidelity and was beneficial for controlled release of biologically active agents such as growth factors.

Calcium phosphate bone cement/mesoporous bioactive glass composites for controlled growth factor delivery.

Calcium phosphate (CaP) bone cements are widely used for the treatment of bone defects and have been proposed to serve as a delivery platform for therapeutic drugs, proteins and growth factors into the defect region. However, they lack sufficient porosity to allow immediate bone ingrowth and thus foster rapid integration into the bone tissue. In this study we investigated a composite prepared from a hydroxyapatite forming bone cement and mesoporous bioactive glass (MBG) granules as a potential carrier for biologically active proteins. The mechanical properties of the composite were not compromised by up to 10 wt% MBG granule addition, which can be attributed to the strong interface between the cement matrix and MBG particles, however this modification induced a significant increase in porosity within 3 weeks ageing in an aqueous liquid. The release profiles of two proteins, lysozyme and the vascular endothelial growth factor (VEGF), could be controlled when they were loaded onto MBG granules that were subsequently embedded into the cement when compared to direct loading into the cement precursor. Both proteins were also demonstrated to maintain their biologic activity during embedding and release from the composite. These findings suggest the CaP bone cement/MBG composite developed in this study as a potential delivery platform for growth factors or other bioactive substances.

Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro.

In this study, the effect of heparin-modified collagen type I/hydroxyapatite (HA) nanocomposites on key processes of bone regeneration - osteogenesis and angiogenesis - was characterised in vitro. Two approaches were applied for heparin modification: it was either integrated during material synthesis (in situ) or added to the porous scaffolds after their fabrication (post). Cultivation of human bone marrow-derived stromal cells (hBMSC), in heparin-modified versus heparin-free scaffolds, revealed a positive effect of the heparin modification on their proliferation and osteogenic differentiation. The amount of heparin rather than the method used for modification influenced the cell response favouring proliferation at smaller amount (30 mg/g collagen) and differentiation at larger amount (150 mg/g collagen). A co-culture of human umbilical vein endothelial cells (HUVEC) and osteogenically induced hBMSC was applied for in vitro angiogenesis studies. Pre-vascular networks have formed in the porous structure of scaffolds which were not modified with heparin or modified with a low amount of heparin (30 mg/g collagen). The modification with higher heparin quantities seemed to inhibit tubule formation. Pre-loading of the scaffolds with VEGF influenced formation and stability of the pre-vascular structures depending on the presence of heparin: In heparin-free scaffolds, induction of tubule formation and sprouting was more pronounced whereas heparin-modified scaffolds seemed to promote stabilisation of the pre-vascular structures. In conclusion, the modification of mineralised collagen with heparin by using both approaches was found to modulate cellular processes essential for bone regeneration; the amount of heparin has been identified to be crucial to direct cell responses.

Synthesis and physicochemical, in vitro and in vivo evaluation of an anisotropic, nanocrystalline hydroxyapatite bisque scaffold with parallel-aligned pores mimicking the microstructure of cortical bone.

Scaffolds for bone regeneration are mostly prepared with an isotropic, sponge-like structure mimicking the architecture of trabecular bone. We have developed an anisotropic bioceramic with parallel aligned pores resembling the honeycomb arrangement of Haversian canals of cortical bone and investigated its potential as a scaffold for tissue engineering. Parallel channel-like pores were generated by ionotropic gelation of an alginate-hydroxyapatite (HA) slurry, followed by ceramic processing. Organic components were thermally removed at 650 °C, whereas the pore system was preserved in the obtained HA bioceramic in the processing stage of a bisque. Even without further sintering at higher temperatures, the anisotropic HA bisque (AHAB) became mechanically stable with a compressive strength (4.3 MPa) comparable to that of native trabecular bone. Owing to the low-temperature treatment, a nanocrystalline microstructure with high porosity (82%) and surface area (24.9 m(2)/g) was achieved that kept the material dissolvable in acidic conditions, similar to osteoclastic degradation of bone. Human mesenchymal stem cells (hMSCs) adhered, proliferated and differentiated into osteoblasts when osteogenically induced, indicating the cytocompatibility of the bisque scaffold. Furthermore, we demonstrated fusion of human monocytes to osteoclast-like cells in vitro on this substrate, similar to the natural pathway. Biocompatibility was demonstrated in vivo by implantation of the bisque ceramic into cortical rabbit femur defects, followed by histological analysis, where new bone formation inside the channel-like pores and generation of an osteon-like tissue morphology was observed.

A novel strontium(II)-modified calcium phosphate bone cement stimulates human-bone-marrow-derived mesenchymal stem cell proliferation and osteogenic differentiation in vitro.

In the present study, the in vitro effects of novel strontium-modified calcium phosphate bone cements (SrCPCs), prepared using two different approaches on human-bone-marrow-derived mesenchymal stem cells (hMSCs), were evaluated. Strontium ions, known to stimulate bone formation and therefore already used in systemic osteoporosis therapy, were incorporated into a hydroxyapatite-forming calcium phosphate bone cement via two simple approaches: incorporation of strontium carbonate crystals and substitution of Ca(2+) by Sr(2+) ions during cement setting. All modified cements released 0.03-0.07 mM Sr(2+) under in vitro conditions, concentrations that were shown not to impair the proliferation or osteogenic differentiation of hMSCs. Furthermore, strontium modification led to a reduced medium acidification and Ca(2+) depletion in comparison to the standard calcium phosphate cement. In indirect and direct cell culture experiments with the novel SrCPCs significantly enhanced cell proliferation and differentiation were observed. In conclusion, the SrCPCs described here could be beneficial for the local treatment of defects, especially in the osteoporotic bone.

Nanocrystalline spherical hydroxyapatite granules for bone repair: in vitro evaluation with osteoblast-like cells and osteoclasts.

Conventionally sintered hydroxyapatite-based materials for bone repair show poor resorbability due to the loss of nanocrystallinity. The present study describes a method to establish nanocrystalline hydroxyapatite granules. The material was prepared by ionotropic gelation of an alginate sol containing hydroxyapatite (HA) powder. Subsequent thermal elimination of alginate at 650 °C yielded non-sintered, but unexpectedly stable hydroxyapatite granules. By adding stearic acid as an organic filler to the alginate/HA suspension, the granules exhibited macropores after thermal treatment. A third type of material was achieved by additional coating of the granules with silica particles. Microstructure and specific surface area of the different materials were characterized in comparison to the already established granular calcium phosphate material Cerasorb M(®). Cytocompatibility and potential for bone regeneration of the materials was evaluated by in vitro examinations with osteosarcoma cells and osteoclasts. Osteoblast-like SaOS-2 cells proliferated on all examined materials and showed the typical increase of alkaline phosphatase (ALP) activity during cultivation. Expression of bone-related genes coding for ALP, osteonectin, osteopontin, osteocalcin and bone sialoprotein II on the materials was proven by RT-PCR. Human monocytes were seeded onto the different granules and osteoclastogenesis was examined by activity measurement of tartrate-specific acid phosphatase (TRAP). Gene expression analysis after 23 days of cultivation revealed an increased expression of osteoclast-related genes TRAP, vitronectin receptor and cathepsin K, which was on the same level for all examined materials. These results indicate, that the nanocrystalline granular materials are of clinical interest, especially for bone regeneration.

In vitro osteoclastogenesis on textile chitosan scaffold.

Textile chitosan fibre scaffolds were evaluated in terms of interaction with osteoclast-like cells, derived from human primary monocytes. Part of the scaffolds was further modified by coating with fibrillar collagen type I in order to make the surface biocompatible. Monocytes were cultured directly on the scaffolds in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL) for up to 18 days. Confocal laser scanning microscopy (CLSM) as well as scanning electron microscopy (SEM) revealed the formation of multinuclear osteoclast-like cells on both the raw chitosan fibres and the collagen-coated scaffolds. The modified surface supported the osteoclastogenesis. Differentiation towards the osteoclastic lineage was confirmed by the microscopic detection of cathepsin K, tartrate resistant acid phosphatase (TRAP), acidic compartments using 3-(2,4-dinitroanillino)-3'-amino-N-methyldipropylamine (DAMP), immunological detection of TRAP isoform 5b, and analysis of gene expression of the osteoclastic markers TRAP, cathepsin K, vitronectin receptor, and calcitonin receptor using reverse transcription-polymerase chain reaction (RT-PCR). The feature of the collagen-coated but also of the raw chitosan fibre scaffolds to support attachment and differentiation of human monocytes facilitates cell-induced material resorption--one main requirement for successful bone tissue engineering.

Response of human bone marrow stromal cells to a novel ultra-fine-grained and dispersion-strengthened titanium-based material.

A novel titanium-based material, containing no toxic or expensive alloying elements, was compared to the established biomaterials: commercially pure titanium (c.p.Ti) and Ti6Al4V. This material (Ti/1.3HMDS) featured similar hardness, yield strength and better wear resistance than Ti6Al4V, as well as better electrochemical properties at physiological pH7.4 than c.p.Ti grade 1 of our study. These excellent properties were obtained by utilizing an alternative mechanism to produce a microstructure of very fine titanium silicides and carbides (<100 nm) embedded in an ultra-fine-grained Ti matrix (365 nm). The grain refinement was achieved by high-energy ball milling of Ti powder with 1.3 wt.% of hexamethyldisilane (HMDS). The powder was consolidated by spark plasma sintering at moderate temperatures of 700 degrees C. The microstructure was investigated by optical and scanning electron microscopy (SEM) and correlated to the mechanical properties. Fluorescence microscopy revealed good adhesion of human mesenchymal stem cells on Ti/1.3HMDS comparable to that on c.p.Ti or Ti6Al4V. Biochemical analysis of lactate dehydrogenase and specific alkaline phosphatase activities of osteogenically induced hMSC exhibited equal proliferation and differentiation rates in all three cases. Thus the new material Ti/1.3HMDS represents a promising alternative to the comparatively weak c.p.Ti and toxic elements containing Ti6Al4V.

In vitro investigations of bone remodeling on a transparent hydroxyapatite ceramic.

The light microscopic examination of cells directly on bioceramic materials in the transmission mode is impossible because many of these materials are opaque. In order to enable direct viewing of living cells and to perform time-lapse studies, nearly transparent bioceramic materials were developed. A dense and fine-grained transparent hydroxyapatite (tHA) was processed by a gel-casting route followed by low-temperature sintering (1000 degrees C). By virtue of its transparency, direct visualization of cellular events on this material is possible in transmitted light. In this study, the interaction of different bone cell types with the tHA ceramic was envisaged. Investigation of rat calvaria osteoblasts (RCO) cultured on tHA by means of transmission light microscopy indicated good cytocompatibility of tHA. Microscopic analysis of osteogenic-induced human bone marrow stromal cells (hBMSC) on tHA and quantitative analysis of their lactate dehydrogenase (LDH) activity at different time points of culture revealed favorable proliferation as well. An increase of the alkaline phosphatase (ALP) activity indicated the differentiation of osteogenic-induced hBMSC towards the osteoblastic lineage. In addition, the differentiation of human monocytes to osteoclast-like cells could also be demonstrated on tHA and was confirmed by fluorescent microscopy imaging of multinucleated cells on the transparent material.

Proliferation and osteogenic differentiation of human bone marrow stromal cells on alginate-gelatine-hydroxyapatite scaffolds with anisotropic pore structure.

Porous mineralized scaffolds are required for various applications in bone engineering. In particular, tube-like pores with controlled orientation inside the scaffold may support homogeneous cell seeding as well as sufficient nutrient supply and may facilitate blood vessel ingrowth. Scaffolds with parallely orientated tube-like pores were generated by diffusion-controlled ionotropic gelation of alginate. Incorporation of hydroxyapatite (HA) during the gelation process yielded stable scaffolds with an average pore diameter of approximately 90 microm. To evaluate the potential use of alginate-gelatine-HA scaffolds for bone tissue engineering, in vitro tests with human bone marrow stromal cells (hBMSCs) were carried out. We analysed biocompatibility and cell penetration into the capillary pores by microscopic methods. hBMSCs were also cultivated on alginate-gelatine-HA scaffolds for 3 weeks in the presence and absence of osteogenic supplements. We studied proliferation and osteogenic differentiation in terms of total lactate dehydrogenase (LDH) activity, DNA content and alkaline phosphatase (ALP) activity and found a 10-14-fold increase of cell number after 2 weeks of cultivation, as well as an increase of specific ALP activity for osteogenic-induced hBMSCs. Furthermore, the expression of bone-related genes [ALP, bone sialoprotein II (BSPII)] was analysed. We found an increase of ALP as well as BSPII expression for osteogenic-induced hBMSCs on alginate-gelatin-HA scaffolds.

In vitro osteogenic potential of human bone marrow stromal cells cultivated in porous scaffolds from mineralized collagen.

Porous 3D structures from mineralized collagen were fabricated applying a procedure in which collagen fibril reassembly and precipitation of nanocrystalline hydroxyapatite (HA) occur simultaneously. The resulting matrices were evaluated in vitro with respect to their suitability as scaffolds for bone tissue engineering. We found a high capacity of the material to bind serum proteins as well as to absorb Ca2+ ions, which could be advantageous to promote cell attachment, growth, and differentiation. Human bone marrow stromal cells (hBMSCs) were seeded onto the 3D scaffolds and cultivated for 4 weeks in the presence and absence of osteogenic supplements. We studied viability, proliferation, and osteogenic differentiation in terms of total lactate dehydrogenase (LDH) activity, DNA content, and alkaline phosphatase (ALP) activity. Furthermore, the expression for bone-related genes (ALP, bone sialo protein II (BSP II), and osteocalcin) was analyzed. In our investigation we found a 2.5-fold to 5-fold raise in DNA content and an increase of ALP activity for osteogenic induced hBMSC on collagen HA scaffolds. The expression of ALP and BSP II in these cells was also stimulated in the course of cultivation; however, we did not detect an upregulation of osteocalcin gene expression. These data suggest, that porous collagen HA scaffolds are suitable for the expansion and osteogenic differentiation of hBMSC and are therefore promising candidates for application as bone grafts.

Heparin modification of calcium phosphate bone cements for VEGF functionalization.

A promising strategy to promote angiogenesis within an engineered tissue is the local and sustained delivery of an angiogenic factor by the substitute itself. Recently, we reported on functionalization of Biocement D (BioD) and several modifications of this calcium phosphate bone cement with vascular endothelial growth factor (VEGF). Maintenance of biological activity of VEGF after release from the cement was improved by modification of BioD with mineralized collagen type I (BioD/coll). However, BioD/coll composites showed a higher initial burst of VEGF release than do the unmodified BioD. In the present study, VEGF release from BioD/coll composites modified with different amounts of heparin was investigated. We found a distinct reduction of the initial burst of release by adding heparin in a concentration-dependent manner. Moreover, the heparin modification had a positive impact on the biological activity of released VEGF. An advancement of biological properties of BioD/coll by addition of heparin was further shown by improved adhesion of endothelial cells on the cement surface. Characterization of material properties of the heparin-modified BioD/coll composites revealed a finer microstructure with smaller HA-particles and a higher specific surface area than heparin-free BioD/coll. However, higher amounts of heparin resulted in a reduced compressive strength. The rheological properties of these cement pastes have been found to be favorable for good handling particularly with regard to their clinical application.

Calcium phosphate bone cements, functionalized with VEGF: release kinetics and biological activity.

Calcium phosphate bone cements are of great interest for bone replacement since the nanocrystalline structure allows their remodelling into native bone tissue. A strategy to accelerate vascularization of the implant region is the functionalization with vascular endothelial growth factor (VEGF), which is known to mediate angiogenesis in vivo. In this study, the release of recombinant human VEGF (rhVEGF(165)) following physical adsorption to Biocement D (BioD) and several modifications were investigated. Our data demonstrate a high VEGF binding capacity of BioD and a sustained release with a moderate initial burst. A proliferation assay using endothelial cells revealed maintenance of biological activity of VEGF after release from BioD. Release behavior of BioD was not improved by modification with mineralized collagen type I, as well as with a combination of mineralized collagen with O-phospho-L-serine and sodium citrate, respectively. In contrast, a positive impact of these modifications on the activity of released VEGF was observed; in case of the phosphoserine- and sodium citrate-modified cements, the biological efficacy of released VEGF was even higher than that of nonreleased control VEGF. We conclude that the bone implant material BioD and, especially, the phosphoserine modification may support activation of angiogenesis by delivery of VEGF in a local and sustained manner.