Research interests

  • Interests
    Cell Culture

Publications

  • 2.19
    Impact points
    Biological functionalization of dental implants with collagen and glycosaminoglycans-A comparative study.

    Bernd Stadlinger, Vera Hintze, Susanne Bierbaum, Stephanie Möller, Matthias C Schulz, Ronald Mai, Eberhard Kuhlisch, Sascha Heinemann, Dieter Scharnweber, Matthias Schnabelrauch, Uwe Eckelt

    Journal of biomedical materials research. Part B, Applied biomaterials. 11/2011;

    Biological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, we hypothesized that the coating of titanium implants with components of the organic extracellular matrix i... [more] Biological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, we hypothesized that the coating of titanium implants with components of the organic extracellular matrix increases bone formation and implant stability compared to an uncoated reference. The implants were coated using collagen-I with either two different concentrations of chondroitin sulfate (CS) or two differentially sulfated hyaluronans. Implant coatings were characterized biochemically and with atomic force microscopy. Histomorphometry was used to assess bone-implant contact (BIC) and bone-volume density (BVD) after 4 and 8 weeks of submerged healing in the maxilla of 20 minipigs. Further, implant stability was measured by resonance frequency analysis (RFA). Implants containing the lower CS concentration had significantly more BIC, compared to the uncoated reference at both times of interest. No significant increase was measured from week 4 to 8. Differences in BVD and RFA were statistically not significant. A higher concentration of CS and the application of sulfated hyaluronans showed no comparable increase in BIC. This study demonstrates a positive effect of a specific collagen-glycosaminoglycan combination on early bone formation in vivo. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
  • 2.92
    Impact points
    Osseointegration - communication of cells.

    Hendrik Terheyden, Niklaus P Lang, Susanne Bierbaum, Bernd Stadlinger

    Clinical oral implants research. 11/2011;

    BACKGROUND: The article provides the scientific documentation for the 3D animated film - "Osseointegration - Communication of cells". AIM: The aim of this article and of the film is to visualise the molecular and cellular events during the healing of an osseous wound after installation of ... [more] BACKGROUND: The article provides the scientific documentation for the 3D animated film - "Osseointegration - Communication of cells". AIM: The aim of this article and of the film is to visualise the molecular and cellular events during the healing of an osseous wound after installation of a dental implant with special emphasis on the process of osseointegration. MATERIAL AND RESULTS: In this review article for didactic reasons the concept of the four phases of a healing soft tissue wound was transferred to a bone wound after insertion of a dental implant: haemostasis, inflammatory phase, proliferative phase and remodelling phase. Wound healing throughout these phases is the result of a coordinated action of different cell types which communicate with each other by their interaction using signalling molecules like cytokines, extracellular matrix proteins and small molecules. A regular sequence of cell types controlled by adequate concentrations of signalling molecules results in undisturbed healing. Disturbed healing is associated with a continuation of the early inflammatory phase and the development of a toxic wound environment. The latter is characterized by high counts of polymorphnuclear cells, high concentrations of toxic radicals and proteolytic enzymes and low concentrations of growth factors and extracellular matrix molecules. Clinically the development of a toxic wound environment should be avoided, e.g. by antibacterial measures. DISCUSSION AND CONCLUSION: Experiencing implant osseointegration as a biological process may provide the clinician new targets to improve the therapy with dental implants.
  • 4.50
    Impact points
    Modifications of Hyaluronan Influence the Interaction with Human Bone Morphogenetic Protein-4 (hBMP-4).

    Vera Hintze, Stephanie Moeller, Matthias Schnabelrauch, Susanne Bierbaum, Manuela Viola, Hartmut Worch, Dieter Scharnweber

    Biomacromolecules. 11/2009;

    In this study, we have demonstrated that the modification of hyaluronan (hyaluronic acid; Hya) with sulfate groups led to different binding affinities for recombinant human bone morphogenetic protein-4 (rhBMP-4). The high-sulfated sHya2.8 (average degree of sulfation (D.S.) 2.8) exhibited the tighte... [more] In this study, we have demonstrated that the modification of hyaluronan (hyaluronic acid; Hya) with sulfate groups led to different binding affinities for recombinant human bone morphogenetic protein-4 (rhBMP-4). The high-sulfated sHya2.8 (average degree of sulfation (D.S.) 2.8) exhibited the tightest interaction with rhBMP-4, followed by the low-sulfated sHya1.0, as determined with surface plasmon resonance (SPR), ELISA, and competition ELISA. Unmodified Hya, chondroitin-sulfate (CS), and heparan sulfate (HS) showed significantly less binding affinity. SPR data could be fitted to an A + B = AB Langmuir model and binding constants were evaluated ranging from 13 pM to 5.45 muM. The interaction characteristics of the differentially sulfated Hyas are promising for the incorporation of these modified polysaccharides in bioengineered coatings of biomaterials for medical applications.
  • 1.96
    Impact points
    Glucuronic acid and phosphoserine act as mineralization mediators of collagen I based biomimetic substrates.

    Ricardo Tejero, Susanne Bierbaum, Timothy Douglas, Antje Reinstorf, Hartmut Worch, Dieter Scharnweber

    Journal of materials science. Materials in medicine. 11/2009;

    Glucuronic acid (GlcA) and phosphoserine (pS) carrying acidic functional groups were used as model molecules for glycosaminoglycans and phosphoproteins, respectively to mimic effects of native biomolecules and influence the mineralization behaviour of collagen I. Collagen substrates modified with Gl... [more] Glucuronic acid (GlcA) and phosphoserine (pS) carrying acidic functional groups were used as model molecules for glycosaminoglycans and phosphoproteins, respectively to mimic effects of native biomolecules and influence the mineralization behaviour of collagen I. Collagen substrates modified with GlcA showed a stable interaction between GlcA and collagen fibrils. Substrates were mineralized using the electrochemically assisted deposition (ECAD) in a Ca(2+)/H( x )PO (4) ((3-x)) electrolyte at physiological pH and temperature. During mineralization of collagen-GlcA matrices, crystalline hydroxyapatite (HA) formed earlier with increasing GlcA content of the collagen matrix, while the addition of pS to the electrolyte succeeded in inhibiting the transformation of preformed amorphous calcium phosphate (ACP) to HA. The lower density of the resulting mineralization and the coalesced aggregates formed at a certain pS concentration suggest an interaction between calcium and the phosphate groups of pS involving the formation of complexes. Combining GlcA-modified collagen and pS-modified electrolyte showed dose-dependent cooperative effects.
  • 3.55
    Impact points
    Increased bone formation around coated implants.

    Bernd Stadlinger, Susanne Bierbaum, Silke Grimmer, Matthias C Schulz, Eberhard Kuhlisch, Dieter Scharnweber, Uwe Eckelt, Ronald Mai

    Journal of clinical periodontology. 07/2009;

    Aim: We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared with uncoated controls. Materials and Methods: Three different implant surface conditions were applied: (1) sandb... [more] Aim: We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared with uncoated controls. Materials and Methods: Three different implant surface conditions were applied: (1) sandblasted acid-etched (control), (2) collagen/chondroitin sulphate (low-dose - CS1), (3) collagen/chondroitin sulphate (high-dose - CS2). Sixty 9.5 mm experimental implants were placed in the mandible of 20 minipigs. Bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD - relation to bone-volume density of the host bone) were assessed after 1 and 2 months of submerged healing. Implant stability was measured by resonance frequency analysis (RFA). Results: After 1 month, coated implants had significantly more BIC compared with controls (CS1: 68%, p<0.0001, CS2: 63%, p=0.009, control: 52%). The rBVD was lower for all surface conditions, compared with the hostbone. After 2 months, BIC increased for all surfaces. No significant differences were measured (CS1: 71%, p=0.016, CS2: 68%, p=0.67, control: 63%). The rBVD was increased for coated implants. RFA values were 71-77 at implantation, 67-73 after 1 month and 74-75 after 2 months. Differences in rBVD and RFA were not statistically significant. Conclusions: Data analysis suggests that collagen/CS has a positive influence on bone formation after 1 month of endosseous healing.
  • 2.92
    Impact points
    Effect of modifications of dual acid-etched implant surfaces on peri-implant bone formation. Part I: organic coatings.

    H Schliephake, A Aref, D Scharnweber, S Bierbaum, A Sewing

    Clinical oral implants research. 02/2009; 20(1):31-7.

    OBJECTIVE: The aim of the present study was to test the hypothesis that peri-implant bone formation can be improved by modifying dual acid-etched (DAE) implant surfaces using organic coatings that enhance cell adhesion and osteogenic differentiation. MATERIAL AND METHODS: Ten adult female foxhounds ... [more] OBJECTIVE: The aim of the present study was to test the hypothesis that peri-implant bone formation can be improved by modifying dual acid-etched (DAE) implant surfaces using organic coatings that enhance cell adhesion and osteogenic differentiation. MATERIAL AND METHODS: Ten adult female foxhounds received experimental titanium implants in the mandible 3 months after removal of all premolar teeth. Six types of implants were evaluated in each animal: (i) implants with a machined surface (MS), (ii) implants with a DAE surface topography, (iii) implants with an acid-etched surface coated with RGD peptides, (iv) implants with an acid-etched surface coated with collagen I, (v) implants with an acid-etched surface coated with collagen I and chondroitin sulphate (CS), (vi) implants with an acid-etched surface coated with collagen I and CS and recombinant human bone morphogenetic protein-2. Peri-implant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the bone volume density (BVD) of the newly formed peri-implant bone. RESULTS: After 1 month, mean BIC was significantly higher in the coated implants group than in the MS group. There was no significant difference when mean BIC in the DAE group was compared with implants with any of the organic coatings, but the difference was significant when compared with the MS implants. Differences in mean BVD value did not reach significance between any of the surfaces. After 3 months, the same held true for the mean BIC of all the groups except for Coll I. Mean volume density of the newly formed bone was higher in all the surface modifications, albeit without statistical significance. CONCLUSIONS: It is concluded that with the exception of Coll I, the tested organic surface coatings on DAE surfaces did not improve peri-implant bone formation when compared with the DAE surfaces but enhanced BIC when compared with the MSs.
  • 2.19
    Impact points
    Suitability of differently designed matrix-based implant surface coatings: An animal study on bone formation.

    Bernd Stadlinger, Eckart Pilling, Matthias Huhle, Evgenij Khavkin, Susanne Bierbaum, Dieter Scharnweber, Eberhard Kuhlisch, Uwe Eckelt, Ronald Mai

    Journal of biomedical materials research. Part B, Applied biomaterials. 06/2008;

    Introduction: The aim of the present study was to assay how bone formation around dental implants is influenced by differently composed collagen matrices and RGD peptide as implant surface coatings compared to a sandblasted titanium surface. Material and Methods: Five different implant surface coati... [more] Introduction: The aim of the present study was to assay how bone formation around dental implants is influenced by differently composed collagen matrices and RGD peptide as implant surface coatings compared to a sandblasted titanium surface. Material and Methods: Five different implant surface coatings were designed: titanium (sandblasted), collagen type I, collagen type I&III, RGD-peptide, and mineralized collagen. Sixty experimental implants of a square-shaped design were inserted into the mandibles of 12 minipigs, 3 months following extraction of the premolar teeth. During the 6-month study period, sequential polyfluorochrome labeling was performed. After sacrifice, bone implant contact (BIC) was evaluated using histologic and histomorphometric methods. Results: New bone formation was observed against all implant surfaces. Polyfluorochrome labeling showed that bone growth started from the host bone in the majority of samples. The highest BIC was measured for collagen I and collagen I/III coated implants; however, significant differences between the coatings could not be found. Conclusion: Osseointegration was achieved for all implant surfaces. Although a statistically significant increase in BIC could not be demonstrated for the experimental coatings after the 6 months study period, there was also no discernible detrimental effect of the coatings in comparison to the uncoated titanium surfaces. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008.
  • 1.96
    Impact points
    Characterization of collagen II fibrils containing biglycan and their effect as a coating on osteoblast adhesion and proliferation.

    Timothy Douglas, Sascha Heinemann, Ute Hempel, Carolin Mietrach, Christiane Knieb, Susanne Bierbaum, Dieter Scharnweber, Hartmut Worch

    Journal of materials science. Materials in medicine. 05/2008; 19(4):1653-60.

    Collagen has been used as a coating material for titanium-based implants for bone contact and as a component of scaffolds for bone tissue engineering. In general collagen type I has been used, however very little attention has been focussed on collagen type II. Collagen-based coatings and scaffolds ... [more] Collagen has been used as a coating material for titanium-based implants for bone contact and as a component of scaffolds for bone tissue engineering. In general collagen type I has been used, however very little attention has been focussed on collagen type II. Collagen-based coatings and scaffolds have been enhanced by the incorporation of the glycosaminoglycan chondroitin sulphate (CS), however the proteglycan biglycan, which is found in bone and contains glycosaminoglycan chains consisting of CS, has not been used as a biomaterial component. The study had the following aims: firstly, five different collagen II preparations were compared with regard to their ability to bind CS and biglycan and the changes in fibril morphology thereby induced. Secondly, the effects of biglycan on the adhesion of primary rat osteoblasts (rO) as well as the proliferation of rO, primary human osteoblasts (hO) and the osteoblast-like cell line 7F2 were studied by culturing the cells on surfaces coated with collagen II fibrils containing biglycan. Fibrils of the collagen II preparation which bound the most biglycan were used to coat titanium surfaces. Bare titanium, titanium coated with collagen II fibrils and titanium coated with collagen II fibrils containing biglycan were compared. It was found that different collagen II preparations showed different affinities for CS and biglycan. In four of the five preparations tested, biglycan reduced fibril diameter, however the ability of a preparation to bind more biglycan did not appear to lead to a greater reduction in fibril diameter. Fibrils containing biglycan promoted the formation of focal adhesions by rO and significantly enhanced the proliferation of hO but not of rO or 7F2 cells. These results should encourage further investigation of biglycan as a component of collagen-based scaffolds and/or coatings.
  • 1.96
    Impact points
    Effect of biological implant surface coatings on bone formation, applying collagen, proteoglycans, glycosaminoglycans and growth factors.

    Bernd Stadlinger, Eckart Pilling, Ronald Mai, Susanne Bierbaum, Ricardo Berhardt, Dieter Scharnweber, Uwe Eckelt

    Journal of materials science. Materials in medicine. 04/2008; 19(3):1043-9.

    OBJECTIVES: The aim of the present study was to evaluate six different implant surface coatings with respect to bone formation. Being major structural components of the extracellular matrix, collagen, the non-collagenous components decorin/chondroitin sulphate (CS) and the growth factors TGF-beta1/B... [more] OBJECTIVES: The aim of the present study was to evaluate six different implant surface coatings with respect to bone formation. Being major structural components of the extracellular matrix, collagen, the non-collagenous components decorin/chondroitin sulphate (CS) and the growth factors TGF-beta1/BMP-4 served in different combinations as coatings of experimental titanium implants. MATERIALS AND METHODS: Eight miniature pigs received each six implants in the mandible. The implant design showed two circular recesses along the length axis. Three, four, five and six weeks after implant placement, the animals were sacrificed in groups of two. Bone-implant contact (BIC) was evaluated along the outer implant surface and within the recesses. Bone volume was determined by synchrotron radiation micro computed tomography (SRmicroCT) for one implant of each surface state, 6 weeks after placement. RESULTS: At each week of observation, collagen/CS or collagen/CS/BMP-4 coated implants showed the highest BIC of all surface states. This was statistically significant at week five (p=0.030, p=0.040) and six (p=0.025, p=0.005). SRmicroCT measurements determined the highest bone volume for a collagen/CS coated implant. CONCLUSION: The results indicate that collagen/CS and collagen/CS/BMP-4 lead to a higher degree of bone formation compared to other ECM components.
  • 2.82
    Impact points
    Influence of collagen-fibril-based coatings containing decorin and biglycan on osteoblast behavior.

    Timothy Douglas, Ute Hempel, Carolin Mietrach, Manuela Viola, Davide Vigetti, Sascha Heinemann, Susanne Bierbaum, Dieter Scharnweber, Hartmut Worch

    Journal of biomedical materials research. Part A. 04/2008; 84(3):805-16.

    Collagen is used as a scaffold material for tissue engineering as well as a coating material for implants with a view to enhancing osseointegration by mimicry of the bone extracellular matrix in vivo. The biomimicry strategy can be taken further by incorporating the small leucine-rich proteoglycans ... [more] Collagen is used as a scaffold material for tissue engineering as well as a coating material for implants with a view to enhancing osseointegration by mimicry of the bone extracellular matrix in vivo. The biomimicry strategy can be taken further by incorporating the small leucine-rich proteoglycans (SLRPs) decorin and biglycan, which are expressed in bone. Both bind to fibrils during fibrillogenesis in vitro. In this study, the ability of collagen types I, II, and III to bind decorin and biglycan was compared. Collagen type II bound significantly more SLRPs in fibrils than collagen I and III, with more biglycan than decorin bound by all three collagen types. Therefore, type II fibrils with bound decorin or biglycan or neither were used to coat titanium surfaces. Bioavailability of SLRPs was confirmed by direct ELISA after SLRP biotinilation. The in vitro behavior of osteoblasts from rat calvaria (rOs) and human knee (hOs) cultured on different surfaces was compared. Proliferation and collagen synthesis were determined. Also, the influence of SLRPs on the formation of focal adhesions by rO was investigated. Biglycan enhanced the formation of focal adhesions after 2 and 24 h. Decorin and biglycan affected rO and hO proliferation and collagen synthesis differently. Biglycan stimulated hO proliferation significantly but had no effect on rO proliferation, and also inhibited rO collagen synthesis significantly while not affecting hO collagen synthesis. Decorin promoted hO proliferation slightly but did not influence rO proliferation. The results could be relevant when designing implant coatings or tissue engineering scaffolds.
  • 1.44
    Impact points
    Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study.

    B Stadlinger, E Pilling, M Huhle, R Mai, S Bierbaum, D Scharnweber, E Kuhlisch, R Loukota, U Eckelt

    International journal of oral and maxillofacial surgery. 01/2008; 37(1):54-9.

    Various studies have shown type I collagen (coll) to increase bone-implant contact (BIC) compared to uncoated implants. The aim of this animal study was to test whether the integration of chondroitin sulphate (CS) and the growth factor rhBMP-4 into a collagenous coating could further increase the me... [more] Various studies have shown type I collagen (coll) to increase bone-implant contact (BIC) compared to uncoated implants. The aim of this animal study was to test whether the integration of chondroitin sulphate (CS) and the growth factor rhBMP-4 into a collagenous coating could further increase the measured BIC compared to collagen coated implants alone. The experimental implants had two recesses along the length axis. 120 implants with the surface modifications: coll, coll/CS, coll/CS/rhBMP-4 were inserted into the mandible of 20 minipigs. Six months after implantation, BIC was measured histomorphometrically on the surface and within the recesses. Due to the specific animal model and strict criteria in placement, 39.2 % of the implants were considered as failure and not included in the analysis. Of the successfully gained 73 implants, the highest percentage of BIC was obtained for coll/CS (40%), followed by coll (30%) and coll/CS/rhBMP-4 (27%), P=0.013. BIC within the recesses was highest for coll/CS (51%), followed by coll (43%) and coll/CS/rhBMP-4 (34%), P=0.025. The result suggests that the inclusion of CS slightly increases the BIC compared to collagen coated implants. The further inclusion of a low amount rhBMP-4 had a detrimental effect on bone formation compared to coll/CS, P<0.05.
  • 2.19
    Impact points
    Influence of extracellular matrix coatings on implant stability and osseointegration: an animal study.

    Bernd Stadlinger, Eckart Pilling, Matthias Huhle, Ronald Mai, Susanne Bierbaum, Ricardo Bernhardt, Dieter Scharnweber, Eberhard Kuhlisch, Ute Hempel, Uwe Eckelt

    Journal of biomedical materials research. Part B, Applied biomaterials. 11/2007; 83(1):222-31.

    Aim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination with collagen, with and without growth factor, can lead to enhanced ossification and thus improve implant stab... [more] Aim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination with collagen, with and without growth factor, can lead to enhanced ossification and thus improve implant stability compared with collagen coatings alone. Twenty miniature pigs received 120 experimental titanium implants in the mandible. Three types of surface coatings were created: (1) collagen type I (coll), (2) collagen type I/chondroitin sulphate (coll/CS), (3) collagen type I/chondroitin sulphate/BMP-4 (coll/CS/BMP). Periimplant bone formation was assessed within a defined recess along the length axis of the implant. Bone-implant contact (BIC) and bone volume density (BVD) were determined, using both histomorphometry and synchrotron radiation micro computed tomography (SRmicroCT). To measure implant stability, resonance frequency analysis was applied after implantation and 1, 3, 7, and 22 weeks after placement. BIC was highest for coll/CS coated implants, followed by coll, p = 0.082. Histomorphometric BVD did not significantly change for any coating. SRmicroCT analysis showed an increased BVD for collagen coated implants, compared with the other two surface coatings. Implant stability showed a decrease for all coatings up to the third week. At 22 weeks, all coatings showed an increase in stability without reaching their initial level. Highest stability was reached for coll coated implants, p = 0.051. It was concluded that collagen and coll/CS implant coatings have advantageous characteristics for peri-implant bone formation, compared with the further integration of BMP-4.
  • 3.11
    Impact points
    In vivo effects of coating loaded and unloaded Ti implants with collagen, chondroitin sulfate, and hydroxyapatite in the sheep tibia.

    Stefan Rammelt, Christian Heck, Ricardo Bernhardt, Susanne Bierbaum, Dieter Scharnweber, Jürgen Goebbels, Jörg Ziegler, Achim Biewener, Hans Zwipp

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 08/2007; 25(8):1052-61.

    The in vivo effects of coating titanium implants with organic extracellular matrix molecules were examined in the sheep tibia. Titanium screws (5.0 mm) were coated with type I collagen (Ti/Coll) or type I collagen and chondroitin sulfate (Ti/Coll/CS) by biomimetic fibrillogenesis. Uncoated screws (T... [more] The in vivo effects of coating titanium implants with organic extracellular matrix molecules were examined in the sheep tibia. Titanium screws (5.0 mm) were coated with type I collagen (Ti/Coll) or type I collagen and chondroitin sulfate (Ti/Coll/CS) by biomimetic fibrillogenesis. Uncoated screws (Ti) and screws coated with hydroxyapatite (Ti/HA) served as control. Six adult female sheep received one screw of each type to stabilize a midshaft tibial fracture with external fixation. Four cylindrical implants of 4-mm outer diameter and 3.3-mm inner diameter with the same coatings were inserted into the tibial head. No pin track infections were seen at the time of implant retrieval 6 weeks after implantation. Extraction torque was greater for Ti/HA (1181 Nmm) and Ti/Coll/CS (1088 Nmm) compared to Ti/Coll (900 Nmm) and Ti (904 Nmm) [N.S.]. Newly formed bone was noted around all coated screws within the medullary cavity. Macrophage and osteoclast activity was significantly reduced around Ti/Coll/CS in both types of implants compared to uncoated controls (p < 0.05). Osteoblast activity was significantly increased around loaded Ti/Coll and Ti/Coll/CS screws compared to uncoated Ti screws (p < 0.05). Microtomographic evaluation (SRmicroCT) revealed no significant differences in new bone formation around the unloaded tibial head implants.Coating of external fixation devices with of type I collagen and chondroitin sulfate appears to have similar effects with respect to stability and bone healing as HA but with less osteoclast activity. These findings were more pronounced under loaded than unloaded conditions in the sheeptibia.
  • 4.50
    Impact points
    Interactions of collagen types I and II with chondroitin sulfates A-C and their effect on osteoblast adhesion.

    Timothy Douglas, Sascha Heinemann, Carolin Mietrach, Ute Hempel, Susanne Bierbaum, Dieter Scharnweber, Hartmut Worch

    Biomacromolecules. 05/2007; 8(4):1085-92.

    Collagen has found use as a scaffold material for tissue engineering as well as a coating material for implants. The main aim of this study was to compare the ability of the collagen types I and II to bind preparations of the chondroitin sulfate types A-C (CS A, CS B, CS C). In addition, the effect ... [more] Collagen has found use as a scaffold material for tissue engineering as well as a coating material for implants. The main aim of this study was to compare the ability of the collagen types I and II to bind preparations of the chondroitin sulfate types A-C (CS A, CS B, CS C). In addition, the effect of the three CS preparations on the extent of collagen incorporated into fibrils and the morphology of collagen fibrils was investigated, as was the influence of collagen fibril coatings containing CS A-C on titanium surfaces on the adhesion of primary rat osteoblasts. Fibrils of both collagen types bound a higher mass of CS C than CS B and a greater mass of CS B than CS A per milligram of fibrils formed. Fibrils of collagen type II bound a higher mass of CS B and C than collagen I fibrils. The proportion of collagen incorporated into fibrils decreased with increasing CS A and CS C concentration but not with increasing CS B concentration. All three CS preparations caused collagen I and II fibrils to become thinner. CS A and CS B but not CS C appeared to stimulate the formation of focal adhesions by osteoblasts after incubation for 2 hours. These results could be of importance when selecting collagen type or CS type as materials for implant coatings or tissue engineering scaffolds.
  • 7.88
    Impact points
    Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate.

    Stefan Rammelt, Till Illert, Susanne Bierbaum, Dieter Scharnweber, Hans Zwipp, Wolfgang Schneiders

    Biomaterials. 11/2006; 27(32):5561-71.

    Coating of orthopaedic implants with extracellular bone matrix components was performed to enhance bone healing. Titanium pins of 0.8mm diameter were coated with type I collagen (Ti/Coll), RGD peptide (Ti/RGD) or type I collagen and chondroitin sulfate (Ti/Coll/CS). Uncoated pins (Ti) served as cont... [more] Coating of orthopaedic implants with extracellular bone matrix components was performed to enhance bone healing. Titanium pins of 0.8mm diameter were coated with type I collagen (Ti/Coll), RGD peptide (Ti/RGD) or type I collagen and chondroitin sulfate (Ti/Coll/CS). Uncoated pins (Ti) served as control. The pins were inserted as intramedullary nails into the tibia of male adult Wistar rats. Six specimens of each group were retrieved at 4, 7, 14 and 28 days. All implants healed uneventfully without adverse reactions. ED 1-positive macrophages appeared in higher numbers around Ti/RGD at day 4 and around Ti at day 14 after implantation (p < 0.05). TRAP-positive osteoclasts and precursors were abundant around Ti/Coll/CS at day 7 (p < 0.05). A significant increase in osteopontin-positive osteoblasts was seen around Ti/Coll/CS implants at days 7 and 14, and around Ti/RGD at day 14 (p < 0.05). At day 28, 62% of Ti, 76% of Ti/Coll, 85%* of Ti/RGD and 89%* of Ti/CoIl/CS (*p < 0.05) implants were covered with newly formed lamellar bone. The addition of extracellular matrix components significantly enhances bone remodelling in the early stages of bone healing around Ti implants, eventually leading to increased new bone formation at the implant surface after 4 weeks.
  • 4.50
    Impact points
    Fibrillogenesis of collagen types I, II, and III with small leucine-rich proteoglycans decorin and biglycan.

    Timothy Douglas, Sascha Heinemann, Susanne Bierbaum, Dieter Scharnweber, Hartmut Worch

    Biomacromolecules. 09/2006; 7(8):2388-93.

    Collagen has found use as a scaffold material for tissue engineering as well as a coating material for implants with a view to enhancing osseointegration through mimicry of the bone extracellular matrix in vivo. The aim of this study was to compare the collagen types I, II, and III with regard to th... [more] Collagen has found use as a scaffold material for tissue engineering as well as a coating material for implants with a view to enhancing osseointegration through mimicry of the bone extracellular matrix in vivo. The aim of this study was to compare the collagen types I, II, and III with regard to their ability to bind the small leucine-rich proteoglycans (SLRPs) decorin and biglycan during fibrillogenesis in vitro in phosphate buffer. In addition, the influence of SLRPs on the proportion of collagen molecules incorporated into fibrils during fibrillogenesis in vitro at high and low ionic strength was investigated, as were their effects on the morphology of collagen fibrils and the speed of fibrillogenesis. Considerably more biglycan than decorin was bound by all three collagen types. Collagen II bound significantly more SLRPs in fibrils than collagen I and III. Decorin and biglycan decreased the proportion of collagen molecules of all three collagen types incorporated into fibrils in similar fashion. Biglycan affected neither fibril diameter nor the speed of fibrillogenesis. Decorin reduced the fibril diameter of all three collagen types. The differences in SLRP-binding ability between collagen types could be of significance when selecting collagen type and/or SLRPs as scaffold materials for tissue engineering or implant coatings.
  • 2.82
    Impact points
    Collageneous matrix coatings on titanium implants modified with decorin and chondroitin sulfate: characterization and influence on osteoblastic cells.

    Susanne Bierbaum, Timothy Douglas, Thomas Hanke, Dieter Scharnweber, Sonja Tippelt, Thomas K Monsees, Richard H W Funk, Hartmut Worch

    Journal of biomedical materials research. Part A. 07/2006; 77(3):551-62.

    Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the s... [more] Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM), utilizing the natural self-assembly potential of collagen in combination with further ECM components in close analogy to the situation in vivo. Aiming at load-bearing applications in bone contact, collagen type I in combination with the proteoglycan decorin and the glycosaminoglycan chondroitin sulfate (CS) was used; fibrillogenesis, fibril morphology, and adsorption of differently composed fibrils onto titanium were assessed. Both decorin and CS could be integrated into the fibrils during fibrillogenesis, the amount bound respectively desorbed depending on the ionic strength of fibrillogenesis buffer. Including decorin always resulted in a significant decrease of fibril diameter, CS in only a slight decrease or even increase, depending on the collagen preparation used. No significant changes in adsorption to titanium could be detected. Osteoblastic cells showed different reactions for cytoskeletal arrangement and osteopontin expression depending on the composition of the ECM, with CS enhancing the osteoblast phenotype.
  • 2.92
    Impact points
    Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation.

    Henning Schliephake, Arash Aref, Dieter Scharnweber, Susanne Bierbaum, Sophie Roessler, Andreas Sewing

    Clinical oral implants research. 11/2005; 16(5):563-9.

    The aim of the present study was to test the hypothesis that immobilization of bone morphogenic protein (BMP2) on the surface of titanium implants can enhance peri-implant bone formation. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal ... [more] The aim of the present study was to test the hypothesis that immobilization of bone morphogenic protein (BMP2) on the surface of titanium implants can enhance peri-implant bone formation. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal of all premolar teeth. Three types of implant surfaces were evaluated in each animal: (i) implants with machined titanium surface, (ii) implants coated with collagen I, (iii) implants coated with collagen I, chondroitin sulphate (CS) and BMP2. Peri-implant bone regeneration was assessed using histomorphometry after 1 and 3 months in five dogs each by measuring bone-implant contact (BIC) and the volume density of the newly formed peri-implant bone (BVD). After 1 month, there was no significant enhancement in BIC values but volume density of the newly formed peri-implant bone was significantly higher in the two groups of coated implants. No significant difference was found between collagen and BMP2 coating. After 3 months, BIC was significantly higher in both collagen and BMP2-coated implants compared with implants with machined surfaces. Peri-implant BVD was also significantly increased in coated implants in comparison with machined surfaces. It was concluded that collagen coating of dental screw implants can enhance BIC and peri-implant bone formation. Addition of BMP2 does not increase peri-implant bone formation in the present application.
  • 3.32
    Impact points
    Collagen type I prevents glyoxal-induced apoptosis in osteoblastic cells cultured on titanium alloy.

    S Tippelt, C Ma, M Witt, S Bierbaum, R H W Funk

    Cells, tissues, organs. 02/2004; 177(1):29-36.

    Advanced glycation end products (AGEs) irreversibly cross-link proteins with sugars and accumulate at a higher age and in diabetes, processes which can interfere with the integration of implants into the tissue. Glyoxal is a highly reactive glycating agent involved in the formation of AGEs and is kn... [more] Advanced glycation end products (AGEs) irreversibly cross-link proteins with sugars and accumulate at a higher age and in diabetes, processes which can interfere with the integration of implants into the tissue. Glyoxal is a highly reactive glycating agent involved in the formation of AGEs and is known to induce apoptosis, as revealed by the upregulation of caspase-3 and fractin (caspase-3 being a key enzyme activated during the late stage of apoptosis and fractin being a caspase-cleaved actin fragment). In this study, we investigated the influence of collagen type I coating on the cytotoxic effect of glyoxal on rat calvarial osteoblastic cells and on human osteosarcoma cells (Saos-2) grown on titanium alloy, Ti6Al4V. Activation of caspase-3 and fractin was measured by counting immunohistochemically stained cells and by flow cytometry with propidium iodide (detection of the apoptosis indicating a sub-G1 peak). Our results showed an increased number of apoptotic osteoblasts after incubation with glyoxal on Ti6Al4V discs. However, the number of apoptotic cells on collagen-coated titanium was significantly smaller than on uncoated titanium after the same treatment. The present findings demonstrate that osteoblasts treated with glyoxal undergo apoptosis, whereas collagen type I coating of titanium alloys (used for implants) has an antiapoptotic function.
  • 2.82
    Impact points
    Modification of Ti6Al4V surfaces using collagen I, III, and fibronectin. I. Biochemical and morphological characteristics of the adsorbed matrix.

    Susanne Bierbaum, René Beutner, Thomas Hanke, Dieter Scharnweber, Ute Hempel, Hartmut Worch

    Journal of biomedical materials research. Part A. 12/2003; 67(2):421-30.

    Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the s... [more] Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM). Aiming at load-bearing applications in bone contact, in this study the modification of titanium surfaces with the collagen types I and III in combination with fibronectin was undertaken; fibrillogenesis, fibril morphology and adsorption of type I, III and I/III-cofibrils onto titanium were assessed. Increasing the collagen type III amount resulted in a decrease of fibril diameter, while no significant changes in adsorption could be detected. The amount of fibronectin bound to the heterotypic fibrils depended on fibrillogenesis parameters such as ionic strength or concentration of phosphate, and varied with the percentage of integrated type III collagen.

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