Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-38058 Zeitschriftenartikel Xin, L.; Bungartz, M.; Maenz, S.; Horbert, V.; Hennig, M.; Illerhaus, Bernhard; Günster, Jens; Bossert, J.; Bischoff, S.; Borowski, J.; Schubert, H.; Jandt, K.; Kunisch, E.; Kinne, R.; Brinkmann, O. Decreased extrusion of calcium phosphate cement versus high viscosity PMMA cement into spongious bone marrow—an ex vivo and in vivo study in sheep vertebrae Vertebroplasty or kyphoplasty of osteoporotic vertebral fractures bears the risk of pulmonary cement embolism (3.5%-23%) caused by leakage of commonly applied acrylic polymethylmethacrylate (PMMA) cement to spongious bone marrow or outside of the vertebrae. Ultraviscous cement and specific augmentation systems have been developed to reduce such adverse effects. Rapidly setting, resorbable, physiological calcium phosphate cement (CPC) may also represent a suitable alternative. PURPOSE: This study aimed to compare the intravertebral extrusion of CPC and PMMA cement in an ex vivo and in vivo study in sheep. STUDY DESIGN/SETTING: A prospective experimental animal study was carried out. METHODS: Defects (diameter 5 mm; 15 mm depth) were created by a ventrolateral percutane-ous approach in lumbar vertebrae of female Merino sheep (2-4 years) either ex vivo (n = 17) or in vivo (n = 6), and injected with: (1) CPC (L3); (2) CPC reinforced with 10% poly(l-lactide-co-glycolide) (PLGA) fibers (L4); or (3) PMMA cement (L5; Kyphon HV-R). Controls were untouched (L1) or empty defects (L2). The effects of the cement injections were assessed in vivo by blood gas analysis and ex vivo by computed tomography (CT), micro-CT (voxel size: 67 µm), histology, and biomechanical testing. Elsevier Inc. 2016 The Spine Journal 16 12 1468 1477 10.1016/j.spinee.2016.07.529 2017-01-03 OPUS4-38429 Zeitschriftenartikel Bungartz, M.; Maenz, S.; Kunisch, E.; Horbert, V.; Xin, L.; Gunella, F.; Mika, J.; Borowski, J.; Bischoff, S.; Schubert, H.; Sachse, A.; Günster, Jens; Illerhaus, Bernhard; Bossert, J.; Jandt, K. D.; Kinne, R. W.; Brinkmann, O. First-time systematic postoperative clinical assessment of a minimally invasive approach for lumbar ventrolateral vertebroplasty in the large animal model sheep Large animal models are highly recommended for meaningful preclinical studies, including the optimization of cement augmentation for vertebral body defects by vertebroplasty/kyphoplasty. The aim of this study was to perform a systematic characterization of a strictly minimally invasive in vivo large animal model for lumbar ventrolateral vertebroplasty. This is a prospective experimental animal study. Lumbar defects (diameter 5 mm; depth approximately 14 mm) were created by a ventrolateral percutaneous approach in aged, osteopenic, female sheep (40 Merino sheep; 6-9 years; 68-110 kg). L1 remained untouched, L2 was left with an empty defect, and L3 carried a defect injected with a brushite-forming calcium phosphate cement (CPC). Trauma/functional impairment, surgical techniques (including drill sleeve and working canula with stop), reproducibility, bone defects, cement filling, and functional cement augmentation were documented by intraoperative incision-to-suture time and X-ray, postoperative trauma/impairment scores, and ex vivo osteodensitometry, microcomputed tomography (CT), histology, static/fluorescence histomorphometry, and biomechanical testing. Minimally invasive vertebroplasty resulted in short operation times (28±2 minutes; mean±standard error of the mean) and X-ray exposure (1.59±0.12 minutes), very limited local trauma (score 0.00±0.00 at 24 hours), short postoperative recovery (2.95±0.29 hours), and rapid decrease of the postoperative impairment score to 0 (3.28±0.36 hours). Reproducible defect creation and cement filling were documented by intraoperative X-ray and ex vivo conventional/micro-CT. Vertebral cement augmentation and osteoconductivity of the CPC was verified by osteodensitometry (CPC>control), micro-CT (CPC>control and empty defect), histology/static histomorphometry (CPC>control and empty defect), fluorescence histomorphometry (CPC>control; all p<.05 for 3 and 9 months), and compressive strength measurements (CPC numerically higher than control; 102% for 3 months and 110% for 9 months). This first-time systematic clinical assessment of a minimally invasive, ventrolateral, lumbar vertebroplasty model in aged, osteopenic sheep resulted in short operation times, rapid postoperative recovery, and high experimental reproducibility. This model represents an optimal basis for standardized evaluation of future studies on vertebral augmentation with resorbable and osteoconductive CPC. Elsevier Inc. 2016 The Spine Journal 16 10 1263 1275 10.1016/j.spinee.2016.06.015 2016-11-24 OPUS4-44561 Beitrag zu einem Sammelband Gunella, F.; Kunisch, E.; Maenz, S.; Horbert, V.; Xin, L.; Mika, J.; Borowski, J.; Bischoff, S.; Schubert, H.; Sachse, A.; Illerhaus, Bernhard; Günster, Jens; Bossert, J.; Jandt, K. D.; Plöger, F.; Kinne, R. W.; Brinkmann, O.; Bungartz, M. Carragee, The GDF5 mutant BB-1 enhances the bone formation induced by an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia BACKGROUND CONTEXT: Targeted delivery of osteoinductive bone morphogenetic Proteins (eg, GDF5) in bioresorbable calcium phosphate cement (CPC), potentially suitable for vertebroplasty and kyphoplasty of osteoporotic vertebral fractures, may be required to counteract augmented local bone catabolism and to support complete bone regeneration. The biologically optimized GDF5 Mutant BB-1 may represent an attractive drug candidate for this purpose. PURPOSE: The aim of the current study was to test an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming CPC containing low-dose BB-1 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages. New York Elsevier 2018 The Spine Journal 18 2 357 369 10.1016/j.spinee.2017.10.002 2018-03-27 OPUS4-52018 Zeitschriftenartikel Xin, L.; Mika, J.; Horbert, V.; Bischoff, S.; Schubert, H.; Borowski, J.; Maenz, S.; Huber, R.; Sachse, A.; Illerhaus, Bernhard; Kinne, R. W. Systematic postoperative assessment of a minimally-invasive sheep model for the treatment of osteochondral defects To assess the clinical course of a sheep stifle joint model for osteochondral (OC) defects, medial femoral condyles (MFC) were exposed without patella luxation using medial parapatellar skin (3-4 cm) and deep incisions (2-3 cm). Two defects (7 mm diameter; 10 mm depth; OC punch) were left empty or refilled with osteochondral autologous transplantation cylinders (OATS) and explanted after six weeks. Incision-to-suture time, anesthesia time, and postoperative wound or impairment scores were compared to those in sham-operated animals. Implant performance was assessed by X-ray, micro-computed tomography, histology, and immunohistology (collagens 1, 2; aggrecan). There were no surgery-related infections or patellar luxations. Operation, anesthesia, and time to complete stand were short (0.5, 1.4, and 1.5 h, respectively). The wound trauma score was low (0.4 of maximally 4; day 7). Empty-defect and OATS animals reached an impairment score of 0 significantly later than sham animals (7.4 and 4.0 days, respectively, versus 1.5 days). Empty defects showed incomplete healing and dedifferentiation/heterotopic differentiation; OATS-filled defects displayed advanced bone healing with remaining cartilage gaps and orthotopic expression of bone and cartilage markers. Minimally-invasive, medial parapatellar surgery of OC defects on the sheep MFC allows rapid and low-trauma recovery and appears well-suited for implant testing. Basel MDPI 2020 Life 10 12 1 14 urn:nbn:de:kobv:b43-520180 10.3390/life10120332 https://creativecommons.org/licenses/by/4.0/deed.de 2021-01-20 OPUS4-43237 Zeitschriftenartikel Gunella, F.; Kunisch, E.; Bungartz, M.; Maenz, S.; Horbert, V.; Xin, L.; Mika, J.; Borowski, J.; Bischoff, S.; Schubert, H.; Hortschansky, P.; Sachse, A.; Illerhaus, Bernhard; Günster, Jens; Bossert, J.; Jandt, K. D.; Plöger, F.; Kinne, R. W.; Brinkmann, O. Low-dose BMP-2 is sufficient to enhance the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia BACKGROUND CONTEXT: Bioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted de- livery of osteoinductive bone morphogenetic Proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration. PURPOSE: This study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic Protein BMP-2 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+ fibers + BMP-2; 1, 5, 100, and 500g BMP-2; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BMP-2) were analyzed ex vivo by measuring (1) bone Mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography [micro-CT] and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineral Apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+ fibers (L4) and/or CPC+ fibers + BMP-2(L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BMP-2, additional significant effects of BMP-2 were demonstrated for bone structure (bone volume/total volume, trabecular thickness, trabecular number) and formation (osteoid surface/bone surface and mineralizing surface/bone surface), as well as for the compressive strength. The BMP-2 effects on bone Formation at 3 and 9 months were dose-dependent, with 5-100g as the optimal dosage. CONCLUSIONS: BMP-2 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤100g BMP-2 was sufficient to augment middle to long-term bone formation. The novel CPC+ BMP-2 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty/kyphoplasty. Elsevier Inc. 2017 The Spine Journal 17 11 1699 1711 10.1016/j.spinee.2017.06.005 2017-12-01 OPUS4-43239 Zeitschriftenartikel Bungartz, M.; Kunisch, E.; Maenz, S.; Horbert, V.; Xin, L.; Gunella, F.; Mika, J.; Borowski, J.; Bischoff, S.; Schubert, H.; Sachse, A.; Illerhaus, Bernhard; Günster, Jens; Bossert, J.; Jandt, K. D.; Plöger, F.; Kinne, R. W.; Brinkmann, O. GDF5 significantly augments the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia BACKGROUND CONTEXT: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. PURPOSE: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic Protein GDF5 was tested in a sheep lumbar osteopenia model. STUDY DESIGN/SETTING: This is a prospective experimental animal study METHODS: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of GDF5 (L5; CPC+ fibers + GDF5; 1, 5, 100, and 500g GDF5; n = 5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months postoperation, structural and functional effects of the CPC (±GDF5) were assessed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), both CPC+ fibers (L4) and CPC+ fibers + GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure. These significant effects were observed both at 3 and 9 months, but for some parameters they were less pronounced at 9 months. Compared with CPC without GDF5, additional significant effects of CPC with GDF5 were demonstrated for BMD and parameters of bone formation and structure (bone volume/total volume, trabecular thickness, and trabecular number, as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5-100g range) at 3 and 9 months. CONCLUSIONS: GDF5 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. The results indicated that a local dose as low as ≤100g GDF5 may be sufficient to augment middle to long-term bone formation. The novel CPC+ GDF5 combination may thus qualify as an alternative to the bioinert, supraphysiologically stiff poly-(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. Elsevier Inc. 2017 The Spine Journal 17 11 1685 1698 10.1016/j.spinee.2017.06.007 2017-12-01 OPUS4-40462 Zeitschriftenartikel Maenz, S.; Brinkmann, O.; Kunisch, E.; Horbert, V.; Gunella, F.; Bischoff, S.; Schubert, H.; Sachse, A.; Xin, L.; Günster, Jens; Illerhaus, Bernhard; Jandt, K. D.; Bossert, J.; Kinne, R. W.; Bungartz, M. Enhanced bone formation in sheep vertebral bodies after minimally invasive treatment with a novel, PLGA fiber-reinforced brushite cement. Injectable, brushite-forming calcium phosphate cements (CPC) show potential for bone replacement, but they exhibit low mechanical strength. This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA) fibers in a minimally invasive, sheep lumbar vertebroplasty model. The study aimed to test the in vivo biocompatibility and osteogenic potential of a PLGA fiber-reinforced, brushite-forming CPC in a sheep large animal model. Elsevier Science direct Elsevier Inc 2017 The Spine Journal 17 5 709 719 10.1016/j.spinee.2016.11.006 2017-06-02 OPUS4-56907 Zeitschriftenartikel Kinne, R. W.; Gunnella, F.; Kunisch, E.; Heinemann, S.; Nies, B.; Maenz, S.; Horbert, V.; Illerhaus, Bernhard; Huber, R.; Firkowska-Boden, I.; Bossert, J.; Jandt, K. D.; Sachse, A.; Bungartz, M.; Brinkmann, O. Performance of calcium phosphate cements in the augmentation of sheep vertebrae - An ex vivo study Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and biocompatibility. In addition, poly(L-lactideco-glycolide) (PLGA) fiber reinforcement may decrease the risk for local extrusion. Bone defects (diameter 5 mm; depth 15 mm) generated ex vivo in lumbar (L) spines of female Merino sheep (2-4 years) were augmented using: (i) water-based CPC with 10% PLGA fiber reinforcement (L3); (ii) Paste-CPC (L4); or (iii) clinically established polymethylmethacrylate (PMMA) bone cement (L5). Untouched (L1) and empty vertebrae (L2) served as controls. Cement performance was analyzed using micro-computed tomography, histology, and biomechanical testing. Extrusion was comparable for Paste-CPC(-PLGA) and PMMA, but significantly lower for CPC + PLGA. Compressive strength and Young's modulus were similar for Paste-CPC and PMMA, but significantly higher compared to those for empty defects and/or CPC + PLGA. Expectedly, all experimental groups showed significantly or numerically lower compressive strength and Young's modulus than those of untouched controls. Ready-to-use Paste-CPC demonstrates a performance similar to that of PMMA, but improved biomechanics compared to those of water-based CPC + PLGA, expanding the therapeutic arsenal for bone defects. O, significantly lower extrusion of CPC + PLGA fibers into adjacent lumbar spongiosa may help to reduce the risk of local extrusion in spinal surgery. Basel MDPI 2021 Materials 14 14 1 12 urn:nbn:de:kobv:b43-569072 10.3390/ma14143873 https://creativecommons.org/licenses/by/4.0/deed.de 2023-01-26