Scaffold development for regenerative medicine

Our research is focused on degradable scaffolds for functional tissue engineering, on polymer processing for implant fabrication as well as the development of innovative implants. Furthermore, our research aims for the characterization and testing of materials and medical implants as well as the development of test procedures for their validation.

Research

Manufacturing processes for application in functional tissue engineering

Solution electrospinning (LES) is a widely utilized process for the fabrication of fiber-based scaffolds. Produced fibers range from several nanometers to a few microns. The achieved macroscopic structures are tunable, depending on the used collector. Applied polymers range from biodegradable PCL, PLA, PEO to piezo-electric PVDF and PVDF-TrFE.

A new fiber production technology based on polymer melts was developed. With the so-called melt electrospinning (MES), the fiber creation is no longer limited by the solubility of polymers. Compared to the solution electrospinning, larger fiber diameters can be obtained.

Electrospraying is similar to electrospinning, but in this case the polymeric solution is atomized resulting in spherical beads with a narrow diameter distribution. These beads can be used to protect incorporated cells, delay drug release as well as to improve cell viability after seeding and facilitate cryopreservtion.

Processing of different polymers (degradable/permanent) and their blends:

degradable: PCL, PLA, PCL/PLA, CS-g-PCL, PEO
permanent: PVDF, PVDF-TrFE, Silicone

Production of individual scaffolds for different fields of application:

The DFG-funded research group FOR2180 aims towards a cell-free, in situ seeding for tendon replacement therapy. Here, graded, electrospun fiber scaffolds with adjusted microstructure as well as mechanical properties are manufactured. Depending on the tissue at the implantation site (muscle, bone), the fiber diameter, inter-fiber distances and wettability are important.

Tissue engineered hAM scaffolds are widely used in e.g. ophthalmology, cardiology, neurology, dermatology and gynecology.

Electrospun blood vessels as TE approach on cardiovascular disease therapy.

Defects in the peripheral nervous system do not heal properly on their own. Electrospun sheets are used as nerve guidance to direct the ends of diseased nerves together and to enable the healing process.

Investigation of flow properties of polymers in solution and the influence on electrospinning and electrospraying.

Standardized characterization of individual novel implant designs

In order to mimic the native tissue, the mechanical properties are as crucial as the biocompatibility. In this context, tensile testing provides information about the reaction of a scaffold to external load.
Both wettability and surface energy significantly determine the type of adsorption on the implant surface (proteins, cells, etc).
The understanding of these mechanisms is fundamental for the engineering of a suiting surface.

Validation of specific test systems for functionality testing (e.g. compliance, calcification, hemocompatibility)

  • Engineering and validation of dynamic test procedures, applying flow or cyclic loading on degradable materials such as magnesium and a broad range of polymers (e.g. PCL, PLA, hydrogels)
  • Investigation of flow conditions and artificial surface interaction for cells and large molecules (e.g. cardiovascular implants) via specific analyzing techniques (e.g. RAMAN) combined with realistic flow models
  • Development of implant specific in vitro test setups combined with methods for surface characterization for testing medical products acc. to DIN EN ISO 10993 standards

GROUP LEADER
Prof. Prof. h.c. Dr.-Ing., M.Sc.
Birgit Glasmacher
Director
Institute for Multiphase Processes
M.Sc.
Alexander du Puits
Research assistant
M.Sc.
Gesine Hentschel
Research assistant
M.Sc.
Diaa Khayyat
Research assistant
M.Eng.
Sara Leal Marin
Research assistant

Publications (excerpt, 2016-2021):

  1. Gryshkov, O., Al Halabi, F., Kuhn, A.I., Leal-Marin, S., Freund, L.J., Förthmann, M., Meier, N., Barker, S.-A., Haastert-Talini, K., Glasmacher, B. Pvdf and P(Vdf-trfe) electrospun scaffolds for nerve graft engineering: a comparative study on piezoelectric and structural properties, and in vitro biocompatibility (2021) International Journal of Molecular Sciences, 22 (21), art. no. 11373, . DOI: 10.3390/ijms222111373
  2. Delp, A., Becker, A., Hülsbusch, D., Scholz, R., Müller, M., Glasmacher, B., Walther, F. In situ characterization of polycaprolactone fiber response to quasi-static tensile loading in scanning electron microscopy (2021) Polymers, 13 (13), art. no. 2090. DOI: 10.3390/polym13132090.
  3. Becker, A., Fricke, D., Roth, B., Glasmacher, B. Assuring Quality of Scaffolds in Musculoskeletal Tissue Engineering Mueller Matrix Polarimetry and Transillumination Imaging (2021) Current Directions in Biomedical Engineering, 7 (2), pp. 179-182. DOI: 10.1515/cdbme-2021-2046.
  4. T. Hildebrand, L. Nogueira, PT Sunde, D. Ørstavik, B. Glasmacher, HJ Haugen. Contrast-enhanced nano-CT reveals soft dental tissues and cellular layers. International Endodontic Journal, 00, 1- 14, 2021.
  5. S. Leal-Marin, T. Kern, N. Hofmann, O. Pogozhykh, C. Framme, M. Börgel, C. Figueiredo, B. Glasmacher, O. Gryshkov. Human amniotic membrane: a review on tissue engineering, application, and storage. J. Biomed. Mater. Res. B 2020, 1-18, https://doi.org/10.1002/jbm.b.34782.

6 S. Suresh, A. Becker, B. Glasmacher. Impact of Apparatus Orientation and Gravity in Electrospinning-A Review of Empirical Evidence. Polymers. 2020; 12(11): 2448.

7 D. Fricke*, A. Becker*, A. Heratizadeh, S. Knigge, L. Jütte, M. Wollweber, T. Werfel, B. W. Roth, B. Glasmacher. Mueller Matrix Analysis of Collagen and Gelatin Containing Samples Towards More Objective Skin Tissue Diagnostics. Polymers. 2020; 12(6): 1400 (* equal contribution).

8 S. Gniesmer, R. Brehm, A. Hoffmann, D. de Cassan, H. Menzel, A.L. Hoheisel, B. Glasmacher, E. Willbold, J. Reifenrath, M. Wellmann, N. Ludwig, F. Tavassol, R. Zimmerer, N.C. Gellrich, A. Kampmann. In vivo analysis of vascularization and biocompatibility of electrospun polycaprolactone fibre mats in the rat femur chamber. Histochem. Cell Biol. 2020;151 (4): 343-356.

9. S. Gniesmer, R. Brehm, A. Hoffmann, D. de Cassan, H. Menzel, A.L. Hoheisel, B. Glasmacher et al. Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair. PloS One 2020;15 (1).

10 D. Fricke*, A. Becker*, L. Jütte, M. Bode, D. de Cassan, M. Wollweber, B. Glasmacher, B. Roth. Mueller Matrix Measurement of Electrospun Fiber Scaffolds for Tissue Engineering. Polymers 2019;11: 2062 (* equal contribution).

11. D. de Cassan, A. Becker, B. Glasmacher, Y. Roger, A. Hoffmann, T. R. Gengenbach, C. D. Easton, R. Hänsch, H. Menzel. Blending chitosan-g-poly(caprolactone) with poly(caprolactone) by electrospinning to produce functional fiber mats for tissue engineering applications. J Appl Polym Sci. 2019;94.

12. D. de Cassan, A.L. Hoheisel, B.Glasmacher, H.Menzel. Impact of sterilization by electron beam, gamma radiation and X-rays on electrospun poly-(ε-caprolactone) fiber mats. J Mater Sci Mater Med. 2019;30 (4): 42.

13 E. Willbold, M. Wellmann, B. Welke, N. Angrisani, S. Gniesmer, A. Kampmann, A. Hoffmann, D. de Cassan, H. Menzel, A. L. Hoheisel, B. Glasmacher, J. Reifenrath. Possibilities and limitations of electrospun chitosan-coated polycaprolactone grafts for rotator cuff tear repair. J Tissue Eng Regen Med. 2019: 1- 12.

14 S. Hügl*, N. Aldag*, A. Becker, T. Lenarz, B. Glasmacher, T. S. Rau. Identification of factors influencing insertion characteristics of cochlear implant electrode carriers. Current Directions in Biomedical Engineering 2019;5 (1): 441-443 (* equal contribution).

15 A. Tretiakov, V. Kapralova, N. Sudar, I. Sapurina, B. Glasmacher, O. Gryshkov. Conductivity switching effect in nanofiber composites modified with conducting polymer. 2019 IEEE International Conference on Electrical Engineering and Photonics (EExPolytech): 236-238, doi: 10.1109/EExPolytech.2019.8906888 .

16. A. Tretikaov, V. Kapralova, N. Sudar, O. Gryshkov, B. Glasmacher. Dielectric properties of PVDF-based thin films and electrospun mats. J. Phys. Conf. Ser. 2019;1236 012009, doi 10.1088/1742-6596/1236/1/012009 .

17. S. Suresh. Improving cell infiltration in electrospun scaffolds for soft tissue engineering (2019) PhD Thesis Hannover Medical School, Hannover.

18. O. Gryshkov, M. Müller, S. Leal-Marin, V. Mutsenko, S. Suresh, V.M. Kapralova, B. Glasmacher. Advances in the application of electrohydrodynamic fabrication for tissue engineering. J. Phys. Conf. Ser. 2019;1236 012024, doi 10.1088/1742-6596/1236/1/012024.

19 S. Suresh, O. Gryshkov, B. Glasmacher. Impact of setup orientation on blend electrospinning of poly-ε-caprolactone-gelatin scaffolds for vascular tissue engineering. Int J Artif Organs 2018;41(11): 801-810.

20 F. Al Halabi, O. Gryshkov, A. I. Kuhn, V. M. Kapralova, B. Glasmacher. Force induced piezoelectric effect of PVDF and PVDF-TrFE scaffolds. Int J Artif Organs 2018;41(11): 811-822.

21. V.M. Kapralova, N.L. Vaskova, E.B. Shadrin, A.V. Ilinsky, O. Gryshkov, B. Glasmacher. Cerebrospinal fluid thermoimpedancemetry as a method of brain diseases diagnostics. Int J Bioelectromagnetism 2018;20(1): 63-65.

22 I.S. Bondarenko, O.G. Avrunin, O. Gryshkov, B. Glasmacher. Possibilities of joint application of acoustic radiation and direct magnetic field for biomedical research. Int J Bioelectromagnetism 2018;20(1): 66-67.

23 F. Al Halabi, O. Gryshkov, A. I. Kuhn, V. M. Kapralova, B. Glasmacher. Piezoelectric properties of PVDF and PVDF-TrFE electrospun materials for nerve regeneration. J Biomed Radioelectron 2018: 123-126.

24. J. Fuchs, M. Mueller, C. Daxböck, M. Stückler, I. Lang et al: Histological processing of un-/ cellularized thermosensitive electrospun scaffolds. In: Histochemistry and Cell Biology 18 (2018), no. 12, 4247. DOI: doi.org/10.1007/s00418-018-1757-7 .

25. S.R. Knigge, B. Glasmacher. Comparison between three in vitro methods to measure magnesium degradation and their suitability for predicting in vivo degradation. Int J Artif Organs 2018;41(11): 772-778.

26 D. de Cassan, S. Sydow, N. Schmidt, P. Behrens, Y. Roger, A. Hoffmann, A.L. Hoheisel, B. Glasmacher, R. Hänsch, H. Menzel. Attachment of nanoparticulate drug-release systems on poly(ε-caprolactone) nanofibers via a graftpolymer as interlayer. Colloids Surf B Biointerfaces 2018;163: 309-320.

27 K. Göke, T. Lorenz, A. Repanas, F. Schneider, D. Steiner, K. Baumann, H. Bunjes, A. Dietzel, J.H. Finke, B. Glasmacher, A. Kwade. Novel strategies for the formulation and processing of poorly water-soluble drugs. Eur J Pharm Biopharm 2018;126: 40-56.

28 C. Feldmann, E. Deniz, A. Stomps, S. Knigge, A. Chatterjee, R. Wendl, J.S. Hanke, G. Dogan, L.C. Napp, B. Glasmacher, A. Haverich, J.D. Schmitto. An acoustic method for systematic ventricular assist device thrombus evaluation with a novel artificial thrombus model. J Thorac Dis. 2018;10(Suppl 15):S1711-S1719.

29 N: Beißner, A. Bolea Albero, J. Füller, T. Kellner, L. Lauterboeck, J. Liang, M. Böl, B. Glasmacher, C.C. Müller-Goymann, S. Reichl. Improved in vitro models for preclinical drug and formulation screening focusing on 2D and 3D skin and cornea constructs. Eur J Pharm Biopharm. 2018; 126: 57-66.

30. m.yu. Tymkovych, O.G. Avrunin, V.G. Paliy, M. Filtsov, O. Gryshkov et al. Automated method for structural segmentation of nasal airways based on cone beam assisted computed tomography. Photonics Applications in Astronomy, Communications, Industry, and High-Energy Physics Experiments 2017, Edition: Proceedings of SPIE, Chapter: 10445, Editors: Romaniuk Ryszard S., Linczuk Maciej, pp.104453F.

31 T. Baudequin, L. Gaut, M. Mueller, A. Huepkes, B. Glasmacher, D. Duprez, F. Bedoui, C. Legallais. The Osteogenic and Tenogenic Differentiation Potential of C3H10T1/2 (Mesenchymal Stem Cell Model) Cultured on PCL/PLA Electrospun Scaffolds in the Absence of Specific Differentiation Medium. Materials 2017;10(12): 1387. DOI: 10.3390/ma10121387.

32 M.I. Rahim, A. Weizbauer, F. Evertz, A. Hoffmann, M. Rohde, B. Glasmacher, H. Windhagen, G. Gross, J. Seitz, P.P. Mueller. Differential magnesium implant corrosion coat formation and contribution to bone bonding. J Biomed Mater Res A 2017;105(3): 697-709.

33 M.I. Rahim, A. Tavares, F. Evertz, M. Kieke, J.M. Seitz, R. Eifler, A. Weizbauer, E. Willbold, H. Jürgen Maier, B. Glasmacher, P. Behrens, H. Hauser, P.P. Mueller. Phosphate conversion coating reduces the degradation rate and suppresses side effects of metallic magnesium implants in an animal model. J Biomed Mater Res B Appl Biomater. 2017;105(6): 1622-1635.

34 M. Granados, L. Morticelli, S. Andriopoulou, P. Kalozoumis, M. Pflaum, P. Lablonskii, B. Glasmacher, M. Harder, J. Hegermann, C. Wrede, I. Tudorache, S. Cebotari, A. Hilfiker, A. Haverich, S. Korossis. Development and Characterization of a Porcine Mitral Valve Scaffold for Tissue Engineering. J Cardiovasc Transl Res. 2017;10(4): 374-390.

35 F. Dencker, L. Dreyer, D. Müller, H. Zernetsch, G. Paasche, R. Sindelar, B. Glasmacher. A silicone fiber coating as approach for the reduction of fibroblast growth on implant electrodes. J Biomed Mater Res B Appl Biomater 2017;105(8): 2574-2580.

36 P. Basu P, A. Repanas, A. Chatterjee, B. Glasmacher, U. Narendra Kumar, I. Manjubala. PEO-CMC blend nanofibers fabrication by electrospinning for soft tissue engineering applications. Materials Letters 2017;195: 10-13.

37. O. Gryshkov, N.I. Klyui, V.P. Temchenko, et al. Porous biomorphic silicon carbide ceramics coated with hydroxyapatite as prospective materials for bone implants. Mater Sci Eng C 2016;68: 143-152.

38 H. Zernetsch, A. Repanas, T. Rittinghaus, M. Mueller, I. Alfred, B. Glasmacher: Electrospinning and Mechanical Properties of Polymeric Fibers Using a Novel Gap-spinning Collector. Fibers and Polymers 2016;17(7): 1025-1032.

39 M. Bensch, M. Mueller, M. Bode, B. Glasmacher. Automation of a test bench for accessing the bendability of electrospun vascular grafts. Current Directions in Biomedical Engineering 2016;2(1): 307-310.

40. A.I. Kuhn, M. Müller, S. Knigge, B. Glasmacher. Novel blood protein-based scaffolds for car-diovascular tissue engineering. Current Directions in Biomedical Engineering 2016;2(1): 5-9.

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Keywords
Biodegradable scaffolds, bioreactors, electrospinning, electrospraying, enamel electrospinning, nerve guidance splints, tendon replacement, piezoelectric membranes, RAMAN imaging and structural analysis, rheology.
Contact

Alexander du Puits M.Sc.

+ 49 (0) 511 762 3823

+ 49 (0) 511 762 4848

dupuits(at)imp.uni-hannover.de

NIFE
AG Glassmaker
Stadtfelddamm 34/ Office S0/2020
30625 Hanover

 

Specials
  1. yESAO exchange award 2021 (to Sara Leal Marin) for "New hydrogels for liver organoids in collaboration" together with Instituto de Investigacion Sanitaria Aragon from Spain.
  2. yESAO exchange award 2022 (to Gesine Hentschel) for " Fabrication of graded polymer fibers for the use in the osteotendinous junction " together with the Laboratoire BioMécanique et Bio-Ingéniérie (BMBI), Université de Technologies de Compiègne, France
  3. Ilse Ter Meer Special Award for the Intercultural Tandem Project (to Ghiath Alkurdi, Sara Leal Marin and Diaa Khayyat), Office for Diversity of Opportunity, Leibniz Universität Hannover

Guest lectures (excerpt):

  1. B. Glasmacher*: Electrospinning is the answer, but what was the question? A versatile technique to fabricate 3D scaffolds, UTC Workshop Tissue Engineering, Compiègne, 22-23.11.2018.
  2. B. Glasmacher*: An Engineer's Contribution to Efficient Vascular Replacement Grafts, Brussels, EAMBES Fellow Inauguration, Brussels Sept. 11, 2018.

 

More additional info

Further research topics and innovations of the research group "Scaffold Engineering" of the Institute for Multiphase Processes are listed here: research/biomaterials

The research group is interested in contract research for industry, internal and external partners regarding the use of equipment, exchange of know-how and development of new methods in the field of "scaffold engineering".

The following devices and methods can be used upon request:

Imaging and characterization methods:

  1. Raman/AFM Microscope - Structural, compositional and surface analysis of materials (laser 532 nm), 3D imaging, AFM contact and AC mode, time series, image stitching
  2. Differential scanning calorimetry (Netzsch) - Quantification of thermal properties

Analysis of cell vitality and functionality:

  1. Cell Viability Analyzer Beckman Coulter Vi-Cell XR - automated and efficient analysis of cell viability by trypan blue staining

Investigation of solution properties:

  1. Rheometer (Rheometrics Fluids Spectrometer RFS II) - viscoelastic properties of hydrogels, analysis of dynamic viscosity of liquids, temperature range 0°C-100°C, different measuring systems (plate-plate, cone-plate and cylinder geometries)
  2. Rotary viscometer HAAKE VT500/VT501 - measuring systems NV, MV1, MV2, MV3, temperature control with an external bath possible
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