NIFE-Hannover
AG „BIODEGRADABLE UND BIOAKTIVE ORTHOPÄDISCHE IMPLANTATE“ (PD Dr. J. Reifenrath)AG „BIODEGRADABLE UND BIOAKTIVE ORTHOPÄDISCHE IMPLANTATE“ (PD Dr. J. Reifenrath)
NIFE-Hannover
Menü

NIFE Video

NIFE - Making-of

Partner

WG „BIODEGRADABLE AND BIOACTIVE ORTHOPEDIC IMPLANTS“ (PD Dr. J. Reifenrath)

Contact info:

PD Dr. med. vet. Janin Reifenrath
Specialist in laboratory animal science
Reifenrath.janin@mh-hannover.de

Deputy:

PD Dr. rer. nat. Elmar Willbold

Staff members:

Dr. med. vet. Nina Angrisani (Veterinarian)
Hilke Catherina Janßen (Veterinarian)
Diana Strauch (lab technician)
Mattias Reebmann (lab technician)
Merle Marie Kempfert (PhD-student)

Orthopedic implants are routinely used in clinics, e.g. in treatment of bone fractures, malalignment or arthroplasties. Nevertheless, difficulties can occur, like foreign body reactions against the implant, osteolytic processes due to stress shielding effects or implant-associated infections. These and other complications can lead to the necessity of implant removal, which is associated with a high patient burden.

Research focuses: degradable implants and implant-associated infections

The research group deals with two major focuses: „biodegradable und bioactive orthopedic implants“. The first is the development of dissolving („biodegradable“) implant materials to supersede a second surgery for implant removal. The second is the evaluation of new concepts for better tissue ingrowth of materials and prevention of implant infections by testing modified (bioactive) implant surfaces. Additionally, new therapeutic strategies are developed. Key questions of biomechanical stability and biocompatibility are examined in this context. Research goal is the development of optimized orthopedic implants and therewith an increased patient safety and quality of life.

Multiple projects, funded by different funding agencies like German Research Foundation (key project was the collaborative research centre 599 „Sustainable bioresorbable and permanent implants of metallic and ceramic materials“), charitable trusts or economical sponsors resulted in a broad spectrum of established and validated methods for implant research and development with special focus on preclinical testing procedures concerning biocompatibility and functionality.

Used methods in this context are in vitro test systems for the evaluation of degradation kinetics or cell-culture experiments to estimate cytotoxicity in a first step. Necessary stability of implants is tested by biomechanical testing procedures like tensile and bending testing as well as cyclic testing. In the further process of preclinical testing, a variety of different specific animal models are established. For detailed quantitative evaluation, for example of implant degradation or bony integration at different time points after surgery, in vivo and ex vivo imaging like radiology, µ-computed tomography, fluorescence imaging or magnetic resonance imaging is used in cooperation with different partners (e.g. Institute of Laboratory Animal Science, Clinic for Laryngology, Rhinology and Otology, both Hannover Medical School or the Veterinary University of Hannover).

Additionally, a variety of histological methods is available. Besides different stainings including fluorescence microscopy, confocal laser scanning microscopy is used in collaboration with the Research Core Unit for Laser Microscopy of MHH for implant surface examination.

In the research focus of implant-associated infections, prophylactic and therapeutic approaches are tested. As prophylactic approach, surface modifications of implants, e.g. by laser structuring (cooperation with Laser Zentrum Hannover), intend to reduce bacterial load while simultaneously increasing tissue integration in bony environment.

In the research focus of new therapeutic strategies for implant infections, a system called „magnetic drug targeting“ is adapted for implant materials. In this strategy, special magnetisable nanoparticles are loaded with chemotherapeutics and accumulated magnetically at the desired location. The advantage shall be a reduction of undesired side effects of medication and a better effectiveness by accumulation at the implant surface and in the direct implant interface. Especially the possibility for treatment at any desired time point after implantation with adequate drug levels around the implant is a promising option which might avoid removal of infected implants.

Services and collaboration

In-vitro-tests

  • Eudiometry

  • Determination of degradation rates of degradable materials in vitro

  • Biomechanical testing of implant materials:

    • After specific intervals

    • In cyclic testing systems

  • Determination of enzyme activity

Preclinical testing of materials in different animal models

  • Clinical examination

  • Radiological examination

  • µ-computed examination

  • Magnetic resonance tomographic examination

  • Confocal laser scanning examination of implant surfaces

  • In vivo fluorescence staining and examination of bone parameters

Histologic

  • Histological processing and evaluation of hard and soft tissue (paraffin and plastic embedding) including residual implant material

  • Staining procedures including antibody staining

  • Microscopic evaluation and documentation by

    • Transmitted light microscopy

    • Dark field microscopy

    • Phase contrast microscopy

    • Fluorescence microscopy

    • Polarisation microscopy

    • Reflectance light microscopy

  • Semiquantitative evaluation of standardised bone parameter

  • Histological-electrochemical dissolving of metals

Actual projects:

  • Graded implants (FOR 2180) --- Tendon to bone interfaces (funder DFG)

  • Implant-directed magnetic drug targeting: antibiotic therapy of periimplant infections (funder DFG)

  • Examination of molecular processes of hip necrosis in comparison to coxarthrosis for the analysis of new therapeutic strategies (funder Erwin Röver Stiftung)

  • reatment of degenerative chondral lesions by the use of osteoproliferative Mg-beads in the subchondral bone plate (funder DFG)

Publications (selection):

In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties.

Janßen HC, Warwas DP, Dahlhaus D, Meißner J, Taptimthong P, Kietzmann M, Behrens P, Reifenrath J, Angrisani N.

J Nanobiotechnology. 2018 Nov 27;16(1):96. doi: 10.1186/s12951-018-0422-6.

Differential Expression of Cholinergic System Components in Human Induced Pluripotent Stem Cells, Bone Marrow-Derived Multipotent Stromal Cells, and Induced Pluripotent Stem Cell-Derived Multipotent Stromal Cells.

Weist R, Flörkemeier T, Roger Y, Franke A, Schwanke K, Zweigerdt R, Martin U, Willbold E, Hoffmann A.

Stem Cells Dev. 2018 Feb 1;27(3):166-183. doi: 10.1089/scd.2017.0162. Epub 2018 Jan 3.

Similar articles Bioabsorbable magnesium versus standard titanium compression screws for fixation of distal metatarsal osteotomies - 3 year results of a randomized clinical trial.

Plaass C, von Falck C, Ettinger S, Sonnow L, Calderone F, Weizbauer A, Reifenrath J, Claassen L, Waizy H, Daniilidis K, Stukenborg-Colsman C, Windhagen H.

J Orthop Sci. 2018 Mar;23(2):321-327. doi: 10.1016/j.jos.2017.11.005. Epub 2017 Nov 23.

Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model.

Bundkirchen K, Macke C, Reifenrath J, Schäck LM, Noack S, Relja B, Naber P, Welke B, Fehr M, Krettek C, Neunaber C.

Clin Orthop Relat Res. 2017 Nov;475(11):2783-2794. doi: 10.1007/s11999-017-5473-8.

Phosphate conversion coating reduces the degradation rate and suppresses side effects of metallic magnesium implants in an animal model.

Rahim MI, Tavares A, Evertz F, Kieke M, Seitz JM, Eifler R, Weizbauer A, Willbold E, Jürgen Maier H, Glasmacher B, Behrens P, Hauser H, Mueller PP.

J Biomed Mater Res B Appl Biomater. 2017 Aug;105(6):1622-1635. doi: 10.1002/jbm.b.33704. Epub 2016 May 6.

Similar articles A comparative study of bone biopsies from the iliac crest, the tibial bone, and the lumbar spine.

Hiller RG, Patecki M, Neunaber C, Reifenrath J, Kielstein JT, Kielstein H.

BMC Nephrol. 2017 Apr 13;18(1):134. doi: 10.1186/s12882-017-0550-5.

Early results using a biodegradable magnesium screw for modified chevron osteotomies.

Plaass C, Ettinger S, Sonnow L, Koenneker S, Noll Y, Weizbauer A, Reifenrath J, Claassen L, Daniilidis K, Stukenborg-Colsman C, Windhagen H.

J Orthop Res. 2016 Dec;34(12):2207-2214. doi: 10.1002/jor.23241. Epub 2016 Apr 7.

Magnesium alloys: A stony pathway from intensive research to clinical reality. Different test methods and approval-related considerations.

Willbold E, Weizbauer A, Loos A, Seitz JM, Angrisani N, Windhagen H, Reifenrath J.

J Biomed Mater Res A. 2017 Jan;105(1):329-347. doi: 10.1002/jbm.a.35893. Epub 2016 Nov

Biocompatibility and degradation of LAE442-based magnesium alloys after implantation of up to 3.5years in a rabbit model.

Angrisani N, Reifenrath J, Zimmermann F, Eifler R, Meyer-Lindenberg A, Vano-Herrera K, Vogt C.

Acta Biomater. 2016 Oct 15;44:355-65. doi: 10.1016/j.actbio.2016.08.002. Epub 2016 Aug 3.

MgNd2 alloy in contact with nasal mucosa: an in vivo and in vitro approach.

Eifler R, Seitz JM, Weber CM, Grundke S, Reifenrath J, Kietzmann M, Lenarz TH, Maier HJ, Klose C, Durisin M.

J Mater Sci Mater Med. 2016 Feb;27(2):25. doi: 10.1007/s10856-015-5636-7. Epub 2015

Examination of a biodegradable magnesium screw for the reconstruction of the anterior cruciate ligament: A pilot in vivo study in rabbits.

Diekmann J, Bauer S, Weizbauer A, Willbold E, Windhagen H, Helmecke P, Lucas A, Reifenrath J, Nolte I, Ezechieli M.

Mater Sci Eng C Mater Biol Appl. 2016 Feb;59:1100-1109. doi: 10.1016/j.msec.2015.11.037.

Corrosion behavior, biocompatibility and biomechanical stability of a prototype magnesium-based biodegradable intramedullary nailing system.

Krämer M, Schilling M, Eifler R, Hering B, Reifenrath J, Besdo S, Windhagen H, Willbold E, Weizbauer A.

Mater Sci Eng C Mater Biol Appl. 2016 Feb;59:129-135. doi: 10.1016/j.msec.2015.10.006. Epub 2015 Oct 3.

Biodegradable nasal stents (MgF2 -coated Mg-2 wt %Nd alloy)-A long-term in vivo study.

Durisin M, Reifenrath J, Weber CM, Eifler R, Maier HJ, Lenarz T, Seitz JM.

J Biomed Mater Res B Appl Biomater. 2017 Feb;105(2):350-365. doi: 10.1002/jbm.b.33559.

The influence of storage and heat treatment on a magnesium-based implant material: an in vitro and in vivo study.

Bracht K, Angrisani N, Seitz JM, Eifler R, Weizbauer A, Reifenrath J.

Biomed Eng Online. 2015 Oct 19;14:92. doi: 10.1186/s12938-015-0091-8.

A novel biodegradable frontal sinus stent (MgNd2): a long-term animal study.

Durisin M, Seitz JM, Reifenrath J, Weber CM, Eifler R, Maier HJ, Lenarz T, Klose C.

Eur Arch Otorhinolaryngol. 2016 Jun;273(6):1455-67. doi: 10.1007/s00405-015-3774-7.