Olaf Brinkmann

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

BACKGROUND CONTEXTnVertebroplasty 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.nnnPURPOSEnThis study aimed to compare the intravertebral extrusion of CPC and PMMA cement in an ex vivo and in vivo study in sheep.nnnSTUDY DESIGN/SETTINGnA prospective experimental animal study was carried out.nnnMETHODSnDefects (diameter 5u2009mm; 15u2009mm depth) were created by a ventrolateral percutaneous 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: 67u2009µm), histology, and biomechanical testing.nnnRESULTSnFollowing ex vivo injection, micro-CT documented significantly increased extrusion of PMMA cement in comparison to CPC (+/- fibers) starting at a distance of 1u2009mm from the edge of the defect (confirmed by histology); this was also demonstrated by micro-CT following in vivo cement injection. In addition, blood gas analysis showed consistently significantly lower values for the fraction of oxygenized hemoglobin/total hemoglobin (FO2Hb) in the arterial blood until 25u2009minutes following injection of the PMMA cement (pu2009≤u2009.05 vs. CPC; 7, 15u2009minutes). Biomechanical testing following ex vivo injection showed significantly lower compressive strength and Young modulus than untouched controls for the empty defect (40% and 34% reduction, respectively) and all three cement-injected defects (21%-27% and 29%-32% reduction, respectively), without significant differences among the cements.nnnCONCLUSIONSnBecause of comparable compressive strength, but significantly lower cement extrusion into spongious bone marrow than PMMA cement, physiological CPC (+/- PLGA fibers) may represent an attractive alternative to PMMA for vertebroplasty or kyphoplasty of osteoporotic vertebral fractures to reduce the frequency or severity of adverse effects.

Enhanced bone formation in sheep vertebral bodies after minimally invasive treatment with a novel, PLGA fiber-reinforced brushite cement.

BACKGROUND CONTEXTnInjectable, 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.nnnPURPOSEnThe 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.nnnSTUDY DESIGN/SETTINGnThis is a prospective experimental animal study.nnnMETHODSnBone defects (diameter: 5u2009mm) were placed in aged, osteopenic female sheep, and left empty (L2) or injected with pure CPC (L3) or PLGA fiber-reinforced CPC (L4; fiber diameter: 25u2009µm; length: 1u2009mm; 10% [wt/wt]). Three and 9 months postoperation (n=20 each), the structural and functional CPC effects on bone regeneration were documented ex vivo by osteodensitometry, histomorphometry, micro-computed tomography (micro-CT), and biomechanical testing.nnnRESULTSnAddition of PLGA fibers enhanced CPC osteoconductivity and augmented bone formation. This was demonstrated by (1) significantly enhanced structural (bone volume/total volume, shown by micro-CT and histomorphometry; 3 or 9 months) and bone formation parameters (osteoid volume and osteoid surface; 9 months); (2) numerically enhanced bone mineral density (3 and 9 months) and biomechanical compression strength (9 months); and (3) numerically decreased bone erosion (eroded surface; 3 and 9 months).nnnCONCLUSIONSnThe PLGA fiber-reinforced CPC is highly biocompatible and its PLGA fiber component enhanced bone formation. Also, PLGA fibers improve the mechanical properties of brittle CPC, with potential applicability in load-bearing areas.

First-time systematic postoperative clinical assessment of a minimally invasive approach for lumbar ventrolateral vertebroplasty in the large animal model sheep

BACKGROUND CONTEXTnLarge animal models are highly recommended for meaningful preclinical studies, including the optimization of cement augmentation for vertebral body defects by vertebroplasty/kyphoplasty.nnnPURPOSEnThe aim of this study was to perform a systematic characterization of a strictly minimally invasive in vivo large animal model for lumbar ventrolateral vertebroplasty.nnnSTUDY DESIGN/ SETTINGnThis is a prospective experimental animal study.nnnMETHODSnLumbar defects (diameter 5u2009mm; depth approximately 14u2009mm) were created by a ventrolateral percutaneous approach in aged, osteopenic, female sheep (40 Merino sheep; 6-9 years; 68-110u2009kg). 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.nnnRESULTSnMinimally invasive vertebroplasty resulted in short operation times (28±2u2009minutes; mean±standard error of the mean) and X-ray exposure (1.59±0.12u2009minutes), very limited local trauma (score 0.00±0.00 at 24u2009hours), short postoperative recovery (2.95±0.29u2009hours), and rapid decrease of the postoperative impairment score to 0 (3.28±0.36u2009hours). 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).nnnCONCLUSIONSnThis 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.

Effects of oxygen plasma treatment on interfacial shear strength and post-peak residual strength of a PLGA fiber-reinforced brushite cement.

Biodegradable calcium phosphate cements (CPCs) are promising materials for minimally invasive treatment of bone defects. However, CPCs have low mechanical strength and fracture toughness. One approach to overcome these limitations is the modification of the CPC with reinforcing fibers. The matrix-fiber interfacial shear strength (ISS) is pivotal for the biomechanical properties of fiber-reinforced CPCs. The aim of the current study was to control the ISS between a brushite-forming CPC and degradable PLGA fibers by oxygen plasma treatment and to analyze the impact of the ISS alterations on its bulk mechanical properties. The ISS between CPC matrix and PLGA fibers, tested in a single-fiber pull-out test, increased up to 2.3-fold to max. 3.22±0.92MPa after fiber oxygen plasma treatment (100-300W, 1-10min), likely due to altered surface chemistry and morphology of the fibers. This ISS increase led to more efficient crack bridging and a subsequent increase of the post-peak residual strength at biomechanically relevant, moderate strains (up to 1%). At the same time, the work of fracture significantly decreased, possibly due to an increased proportion of fractured fibers unable to further absorb energy by frictional sliding. Flexural strength and flexural modulus were not affected by the oxygen plasma treatment. This study shows for the first time that the matrix-fiber ISS and some of the resulting mechanical properties of fiber-reinforced CPCs can be improved by chemical modifications such as oxygen plasma treatment, generating the possibility of avoiding catastrophic failures at the implant site and thus enhancing the applicability of biodegradable CPCs for the treatment of (load-bearing) bone defects.

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 CONTEXTnBiodegradable 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.nnnPURPOSEnIn 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.nnnSTUDY DESIGN/SETTINGnThis is a prospective experimental animal study.nnnMETHODSnDefined bone defects (diameter 5u2009mm) 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 500u2009µg 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.nnnRESULTSnCompared 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 5-100u2009µg range) at 3 and 9 months.nnnCONCLUSIONSnGDF5 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 ≤100u2009µg 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.

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 CONTEXTnBioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted delivery of osteoinductive bone morphogenetic proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration.nnnPURPOSEnThis 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.nnnSTUDY DESIGN/ SETTINGnThis is a prospective experimental animal study.nnnMETHODSnBone defects (diameter 5u2009mm) 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 500u2009µg 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.nnnRESULTSnCompared 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 5-100u2009µg as the optimal dosage.nnnCONCLUSIONSnBMP-2 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤100u2009µg 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.

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 CONTEXTnTargeted 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.nnnPURPOSEnThe 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.nnnSTUDY DESIGN/ SETTINGnThis is a prospective experimental animal study.nnnMETHODSnBone defects (diameter 5u2009mm) were generated in aged, osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BB-1 (L5; CPC+fibers+BB-1; 5, 100, and 500u2009µg BB-1; n=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 (±BB-1) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (BV/TV) (assessed by micro-CT and histomorphometry), trabecular thickness (Tb.Th), and trabecular number (Tb.N); (3) bone formation, that is, osteoid volume/bone volume (OV/BV), osteoid surface/bone surface (OS/BS), osteoid thickness, mineralizing surface/bone surface (MS/BS), mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength.nnnRESULTSnCompared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BB-1 (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 BB-1, additional significant effects of BB-1 were demonstrated for BMD, bone structure (BV/TV, Tb.Th, and Tb.N), and bone formation (OS/BS and MS/BS). The BB-1 effects on bone formation at 3 and 9 months were dose dependent, with 100u2009µg as the potentially optimal dosage.nnnCONCLUSIONSnBB-1 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as 100u2009µg BB-1 was sufficient to augment middle- to long-term bone formation. A CPC containing the novel GDF5 mutant BB-1 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty and kyphoplasty.

Management of knee dislocation prior to ligament reconstruction: What is the current evidence? Update of a universal treatment algorithm

Traumatic knee dislocation is a rare but potentially limb-threatening injury. Thus proper initial diagnosis and treatment up to final ligament reconstruction are extremely important and a precondition to successful outcomes. Reports suggest that evidence-based systematic approaches lead to better results. Because of the complexity of this injury and the inhomogeneity of related literature, there are still various controversies and knowledge gaps regarding decision-making and step-sequencing in the treatment of acute multi-ligament knee injuries and knee dislocations. The use of ankle-brachial index, routine or selective angiography, braces, joint-spanning or dynamic external fixation, and the necessity of initial ligament re-fixation during acute surgery constitutes current topics of a scholarly debate. The aim of this article was to provide a comprehensive literature review bringing light into some important aspects about the initial treatment of knee dislocation (vascular injury, neural injury, immobilization techniques) and finally develop an accurate data-based universal algorithm, enabling attending physicians to become more acquainted with the management of acute knee dislocation.

In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model

Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the “host” cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

Cemented conical stems can be removed more easily than cylindrical stems, regardless of cone angle in revision knee arthroplasty

BackgroundAccording to literature, more than 30% of revised knee arthroplasties will require at least one re-revision. Practical experience has shown that there are considerable product-specific differences in the explantability of cemented long-stem prostheses. In the registers of successful implants, stem geometry varies considerably between the manufacturers. However, comparative data on explantability of the respective stems are missing. Objective of the present study was to identify a correlation between the geometry of a smooth cemented long stem and the necessary explantation energy required until failure of the implant–cement interface occurs.MethodsEight cemented stems with different conical profile angles (0°–3°) were explanted in a reproducible biomechanical setup each six times to evaluate the correlation between the stem design and the required explantation energy.ResultsThe average explantation energy was highest in the case of the cylindrical stem, at 18.1u2009±u20093.6xa0J. At a cone angle of 0.25°, it was just 12.1u2009±u20092.1xa0J (pu2009<u20090.001) and dropped beyond 0.5° to an average of 5.7u2009±u20091.8xa0Jxa0(pxa0<xa00.001). Between 0.5° and 3°, no significant difference in the required extraction energy was observed.ConclusionsWhereas smooth conical stems can mostly be removed easily, an early decision in favour of osteotomy or fenestration can be taken in the case of cylindrical cemented stems.