• Laser Structuring on Medical-Grade

    Borcherding K et al., Materials (Basel). 2020 Apr 24;13(8):2000. doi: 10.3390/ma13082000. PMID: 32344699

  • Impact Bone Regeneration

    Schlundt C et. al., Front Immunol. 2019 Aug 16;10:1954.doi: 10.3389/fimmu.2019.01954. eCollection 2019

  • Ankle Bracing on Kinematics

    Agres AN et al., Am J Sports Med. 2019 May;47(6):1480-1487. doi: 10.1177/0363546519837695.

  • When to reimplant after joint infection?

    Winkler et at., Arch Orthop Trauma Surg 2019; 139(4):295-303.

  • Petersen et al.; Nature Communications; 2018

    Biomaterial-induced endochondral ossification to heal bone defects

  • Eckstein F. et al.; Osteoarthritis Cartilage; 2018

    Normal knee joints with contralateral joint space narrowing may serve as human model of early OA

  • Muscle co-contraction stongly increases knee loads

    Trepczynski et al.; J Neuroeng Rehabil.; 2018

  • Klein et al.; Sci Rep.; 2018

    MALDI-IMS revealed that early molecular alterations occur largely in the region adjacent to the trauma

  • Lueckgen et al.; Biomaterials; 2018

    Hydrolytically-degradable click-crosslinked alginate hydrogels

  • Moll et al.; Trends in Molecular Medicine; 2019

    Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines

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Ausgewählte Publikationen

  • Borcherding K, Marx D, Gätjen L, Specht U, Salz D, Thiel K, Wildemann B, Grunwald I

    Impact of Laser Structuring on Medical-Grade Titanium: Surface Characterization and In Vitro Evaluation of Osteoblast Attachment

    A laser treatment to structure standard titanium alloy implants for improved osteointegration offers meaningful potential for orthopedic implants. The objective of this study was to characterize the pore structure shape, treatment‐related metallographic changes, cytocompatibility, and attachment of osteoblast‐like cells (MG‐63).The pore dimensions were a bottleneck diameter of 27 μm, an inner pore width of 78 μm, and a pore depth of 129 μm. The introduced energy of the laser changed the metallic structure of the alloy within the heat‐affected region (approximately 66 μm) without any indication of a micro cracking formation. Cell viability was improved on the structured surface compared to pure titanium, indicating good cytocompatibility.

    Materials (Basel) 2020; 13(8)

  • Fleischhacker V, Klatte-Schulz F, Minkwitz S, Schmock A, Rummler M, Seliger A, Willie BM, Wildemann B

    In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes-A Pilot Study

    Mechanical force is a key factor for the maintenance, adaptation, and function of tendons. Investigating the impact of mechanical loading in tenocytes and tendons might provide important information on in vivo tendon mechanobiology. Therefore, the study aimed at understanding if an in vitro loading set up of tenocytes leads to similar regulations of cell shape and gene expression, as loading of the Achilles tendon in an in vivo mouse model. This study showed that the gene expression of tendon markers was similar, whereas significant changes in cell shape and the expression of extracellular matrix (ECM) related genes were detected between in vivo and in vitro loading.
    This first pilot study is important for understanding to which extent in vitro stimulation set-ups of tenocytes can mimic in vivo characteristics.

    Int J Mol Sci 2020; 21(4)

  • Schlundt C, Reinke S, Geissler S, Bucher CH, Giannini C, Märdian S, Dahne M, Kleber C, Samans B, Baron U, Duda GN, Volk HD, Schmidt-Bleek K

    Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration

    There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration Using adoptive TReg transfer, bone healing was consistently improved in mice possessing an inexperienced immune system with low amounts of CD8+ TEFF. In contrast, mice with an experienced immune system (high amounts of CD8+ TEFF) showed heterogeneous bone repair with regeneration being dependent upon the individual TEFF/TReg ratio. Thus, the healing outcome can only be improved by an adoptive TReg therapy, if an unfavorable TEFF/TReg ratio can be reshaped; if the individual CD8+ TEFF percentage, which is dependent on the individual immune experience can be changed toward a favorable ratio by the TReg transfer.

    Front Immunol 2019; 10

  • Bucher C, Schlundt C, Wulsten D, Sass F, Wendler S, Ellinghaus A, Thiele T, Seemann R, Willie B, Volk H, Duda G, Schmidt-Bleek K

    Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing

    Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Bone formation is impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. Considering the immune system's experience level will likely allow a more effective differentiation (stratify) and treatment (immune-modulate) of patients .

    Front Immunol 2019; 10:797.

  • Agres AN, Chrysanthou M, Raffalt PC

    The Effect of Ankle Bracing on Kinematics in Simulated Sprain and Drop Landings: A Double-Blind, Placebo-Controlled Study.

    The efficacy of external ankle braces to protect against sudden inversion sprain has yet to be determined while taking into account the possible placebo effect of brace application. To assess the protective effect of an external ankle brace on ankle kinematics during simulated inversion sprain and single-legged drop landings among individuals with a history of unilateral lateral ankle sprain. The primary hypothesis was that active and placebo external braces would reduce inversion angle during simulated inversion sprain. Sixteen participants with ankle instability and previous sprain performed single-legged drop landings and sudden inversion tilt perturbations. Kinematics of the affected limb were assessed in 3 conditions (active bracing, passive placebo bracing, and unbraced) across 2 measurement days. Participators and investigators were blinded to the brace type tested. The effect of bracing on kinematics was assessed with repeated measures analysis of variance with statistical parametric mapping, with post hoc tests performed for significant interactions. Only active bracing reduced inversion angles during a sudden ankle inversion when compared with the unbraced condition. This reduction was apparent between 65 and 140 milliseconds after the initial fall. No significant differences in inversion angle were found between the passive placebo brace and unbraced conditions during sudden ankle inversion. Furthermore, no significant differences were found among all tested conditions in the sagittal plane kinematics at the knee and ankle. During an inversion sprain, only the actively protecting ankle brace limited inversion angles among participants. These results do not indicate a placebo effect of external bracing for patients with ankle instability and a history of unilateral ankle sprain. Furthermore, sagittal plane knee kinematics appear to remain unaffected by bracing during single-legged landing, owing to the limited effects of bracing on sagittal ankle kinematics. These results highlight the role of brace design on biomechanical function during sports-related and injury-prone movements.

    Am J Sports Med 2019; 47(6):1480-1487.

  • Winkler T, Perka C, von Roth P, Agres AN, Plage H, Preininger B, Pumberger M, Geissler S, Hagai EL, Ofir R, Pinzur L, Eyal E, Stoltenburg-Didinger G, Meisel C, Consentius C, Streitz M, Reinke P, Duda GN, Volk HD

    Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty

    In this study we addressed surgical trauma-related muscle injuries resulting from Hip arthroplasty by local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD). This cell type was used because of its high regenerative and immunomodulatory potency and we could show that this allogeneic PLX-PAD therapy improved strength and volume of the injured skeletal muscle with a reasonable safety profile. Outcomes could be positively correlated with the modulation of early postoperative stress-related immunological reactions.

    J Cachexia Sarcopenia Muscle 2018; 9(5):880-897.

  • Petersen A, Princ A, Korus G, Ellinghaus A, Leemhuis H, Herrera A, Klaumunzer A, Schreivogel S, Woloszyk A, Schmidt-Bleek K, Geissler S, Heschel I, Duda GN

    A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects

    Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. In contrast, most bones in our body develop from a cartilage template via a second pathway called endochondral ossification. Here we report on a biomaterial with a channel-like pore architecture to control cell recruitment and tissue patterning in the early phase of healing. In consequence of extracellular matrix alignment, CD146+ progenitor cell accumulation and restrained vascularization, a highly organized endochondral ossification process is induced in rats. It demonstrates that a pure biomaterial approach can recapitulate a developmental bone growth process.

    Nat Commun 2018; 9(1):4430.

  • Eckstein F, Maschek S, Roemer FW, Duda GN, Sharma L, Wirth W

    Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative

    OBJECTIVE: To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. CONCLUSIONS: Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

    Osteoarthritis Cartilage 2019; 27(2):273-277.

  • Trepczynski A, Kutzner I, Schwachmeyer V, Heller MO, Pfitzner T, Duda GN

    Impact of antagonistic muscle co-contraction on in vivo knee contact forces

    BACKGROUND: The onset and progression of osteoarthritis, but also the wear and loosening of the components of an artificial joint, are commonly associated with mechanical overloading. Mechanical forces acting at the joints and understanding of the key factors that can alter them are critical to develop effective treatments for restoring joint function. While static anatomy is usually the clinical focus, less is known about the impact of dynamic factors, such as individual muscle recruitment, on joint contact forces. CONCLUSIONS: Treatment of diseased and failed joints should not only be restricted to anatomical reconstruction of static limb axes alignment. The dynamic activation of muscles, as a key modifier of lower limb biomechanics, should also be taken into account and thus also represents a promising target for restoring function, patient mobility, and preventing future joint failure. German Clinical Trials Register: ID: DRKS00000606

    J Neuroeng Rehabil 2018; 15(1):101.

  • Lueckgen A, Garske DS, Ellinghaus A, Desai RM, Stafford AG, Mooney DJ, Duda GN, Cipitria A

    Hydrolytically-degradable click-crosslinked alginate hydrogels

    Degradable biomaterials aim to recapitulate the dynamic microenvironment that cells are naturally exposed to. By oxidizing the alginate polymer backbone, thereby rendering it susceptible to hydrolysis, and crosslinking it via norbornene-tetrazine click chemistry, we can control rheological, mechanical, and degradation properties of resulting hydrogels. The degradation behavior was verified by tracking mechanical and swelling behavior over time, showing that degradation could be decoupled from initial mechanical properties. Cells attached, spread and proliferated in 2D and retained a round morphology and stable number in 3D, while maintaining high viability in both contexts over 7 days. Finally, oxidized and unoxidized control materials were implanted subcutaneously into the backs of C57/Bl6 mice, and recovered after 8 weeks. Histological staining revealed morphological differences and fibrous tissue infiltration only in oxidized materials.

    Biomaterials 2018; 181:189-198.

  • Klein O, Strohschein K, Nebrich G, Fuchs M, Thiele H, Giavalisco P, Duda GN, Winkler T, Kobarg JH, Trede D, Geissler S

    Unraveling local tissue changes within severely injured skeletal muscles in response to MSC-based intervention using MALDI Imaging mass spectrometry

    Despite our increasing understanding of molecular and cellular mechanisms of MSCs regenerative function, little is known about the local molecular alterations and their spatial distribution within the tissue after autologous bone marrow MSC transplantation. Using MALDI imaging mass spectrometry and multivariate statistical strategies we revealed that very early molecular alterations in response to MSC transplantation occur largely in the region adjacent to the trauma and only to a small extent in the actual trauma region. We subsequently identified the proteins in the specific muscle regions.

    Sci Rep 2018; 8(1):12677.

  • Moll G, Ankrum JA, Kamhieh-Milz J, Bieback K, Ringden O, Volk HD, Geissler S, Reinke P

    Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines

    Intravascular infusion is the most popular route for therapeutic multipotent mesenchymal stromal/stem cell (MSC) delivery in hundreds of clinical trials. Meta-analysis has demonstrated that bone marrow MSC infusion is safe. It is not clear if this also applies to diverse new cell products derived from other sources, such as adipose and perinatal tissues. Different MSC products display varying levels of highly procoagulant tissue factor (TF) and may adversely trigger the instant blood-mediated inflammatory reaction (IBMIR). Suitable strategies for assessing and controlling hemocompatibility and optimized cell delivery are crucial for the development of safer and more effective MSC therapies.

    Trends Mol Med 2019; 25(2):149-163.

  • Winkler T, Stuhlert MGW, Lieb E, Muller M, von Roth P, Preininger B, Trampuz A, Perka CF

    Outcome of short versus long interval in two-stage exchange for periprosthetic joint infection: a prospective cohort study

    For chronic periprosthetic joint infection, a 6-8 week interval is commonly used before re-implantation. We evaluated the influence of a short (< 4 weeks) and long (>/= 4 weeks) prosthesis-freeinterval on reinfection rate and functional outcome of hip and knee periprosthetic joint infection. Our study suggests that two-stage exchange with short interval has a similar outcome than with long interval, when highly active antibiotic therapy is used. Patient inconvenience and care costs due to immobilization were lower when strategies with a short interval were used.

    Arch Orthop Trauma Surg 2019; 139(4):295-303.

  • Lang A, Kirchner M, Stefanowski J, Durst M, Weber MC, Pfeiffenberger M, Damerau A, Hauser AE, Hoff P, Duda GN, Buttgereit F, Schmidt-Bleek K, Gaber T

    Collagen I-based scaffolds negatively impact fracture healing in a mouse-osteotomy-model although used routinely in research and clinical application

    Clinical application of bone morphogenetic protein 2 is only approved when applied on an absorbable bovine collagen I scaffold (ACS). Nevertheless, the influence of ACS alone on bone healing remains so far unknown. In vitro studies using ASC-H (Helistat) revealed a suppression of osteogenic differentiation and a reduction of cell vitality compared to ASC-L, another frequently used scaffold. In vivo, a significant delay in bone healing was observed when ACS-L was applied during femoral osteotomy. This negative influence of ACS-H and ACS-L on bone formation demonstraties a substantial need for more sophisticated delivery systems for local stimulation of bone healing.

    Acta Biomater 2019; 86:171-184.