A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures

Alt, Volker; Thormann, Ulrich; Ray, Seemun; Zahner, Daniel; Dürselen, Lutz; Lips, Katrin Susanne; Khassawna, Thaqif El; Heiß, Christian; Riedrich, Alina; Schlewitz, Gudrun; Ignatius, Anita; Kampschulte, Marian; Dewitz, Helena von; Heinemann, Sascha; Schnettler, Reinhard; Langheinrich, Alexander C.

doi:10.1016/j.actbio.2013.02.002

Cited by 77 publications

(62 citation statements)

References 35 publications

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“…The second group of samples was utilized from 4 mm wedge-shaped metaphyseal defect at the distal end of the left femur as described previously [11]. The fracture gap was filled with strontium-doped CPC (SrCPC) to enhance healing in the osteoporotic rat fracture model.…”

Section: Methodsmentioning

confidence: 99%

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

Khassawna

Daghma

Stoetzel

et al. 2017

BioMed Research International

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Bone histology of decalcified or undecalcified samples depends on the investigation. However, in research each method provides different information to answer the scientific question. Decalcification is the first step after sample fixation and governs what analysis is later feasible on the sections. Besides, decalcification is favored for immunostaining and in situ hybridization. Otherwise, sample decalcification can be damaging to bone biomaterials implants that contains calcium or strontium. On the other hand, after decalcification mineralization cannot be assessed using histology or imaging mass spectrometry. The current study provides a solution to the hardship caused by material presence within the bone tissue. The protocol presents a possibility of gaining sequential and alternating decalcified and undecalcified sections from the same bone sample. In this manner, investigations using histology, protein signaling, in situ hybridization, and mass spectrometry on the same sample can better answer the intended research question. Indeed, decalcification of sections and grindings resulted in well-preserved sample and biomaterials integrity. Immunostaining was comparable to that of classically decalcified samples. The study offers a novel approach that incites correlative analysis on the same sample and reduces the number of processed samples whether clinical biopsies or experimental animals.

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Section: Methodsmentioning

confidence: 99%

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

Khassawna

Daghma

Stoetzel

et al. 2017

BioMed Research International

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“…The size of the gap was generated precisely with a size of 3 ± 0.21 mm and 5 ± 0.24 mm, respectively. Quantitative µCT analysis demonstrated a completely healed 3 mm gap (Figure 2A-C) but a persistent gap without any cortical bridging of the fracture defect of 5 mm ( Figure 2D-F) after 42 days post-osteotomy [48]. Additionally, histological analysis showed signs of a non-healed critical-size defect with fibrous tissue inside the persistent defect zone without cortical bridging as well [48].…”

Section: Animal Modelsmentioning

confidence: 99%

“…Quantitative µCT analysis demonstrated a completely healed 3 mm gap (Figure 2A-C) but a persistent gap without any cortical bridging of the fracture defect of 5 mm ( Figure 2D-F) after 42 days post-osteotomy [48]. Additionally, histological analysis showed signs of a non-healed critical-size defect with fibrous tissue inside the persistent defect zone without cortical bridging as well [48]. These findings are in line with findings from Mehta et al [20] who generated an atrophic non-union in female rats even with normal bone status after 6 weeks in the diaphysis of the rats' femur.…”

Section: Animal Modelsmentioning

confidence: 99%

“…A recently published consensus paper by Garcia et al [10] about non-union and critical-size defects in rodent animal models as well as a comprehensive review of "In vivo models of bone repair" by Mills et al [47] concluded that there is still an absence of metaphyseal fracture-defect models in osteoporotic bone. In our own work group, we recently published a new metaphyseal fracturedefect model [48], which is focused on a critical-size defect to allow for characterization of biomaterials in osteoporotic bone induced by bilaterally ovariectomy and multi-deficiencies-diet [49,50]. This fracture-defect model consists of a wedge-shaped osteotomy at the distal metaphysis of the femur.…”

Section: Animal Modelsmentioning

confidence: 99%

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Biomaterials for enhancement of bone healing in osteoporotic fractures

Thormann¹,

Ray

Sommer

et al. 2013

BioNanoMaterials

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Osteoporosis and osteoporotic fractures have a high impact on the quality of life of patients and on the financial aspects of Western health care systems. There is a tremendous need for improvement of the treatment outcome in osteoporotic fracture patients and biomaterials are of interest to stimulate fracture healing in those patients. For adequate characterization of biomaterials for the indication of osteoporotic fractures a clinically relevant animal model with a fracture defect in the metaphyseal region of a long bone in an osteoporotic animal is required. We recently developed a 3-5 mm wedge shaped osteotomy model in the distal metaphysis of the femur in osteoporotic rats. There are different biomaterials approaches to stimulate fracture healing in osteoporotic fractures and recently published results suggest that the composite implants from osteoconductive carriers combined with osteoanabolic agents, e.g., strontium-modified calcium phosphate cement, can enhance new bone formation. Further in vivo and clinical research will be necessary in the future for introduction of new and different types of biomaterials for osteoporotic fracture patients into all day clinical practice.

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“…The aim of the present study was to identify the lymphatic vessels in a rat model of osteoporotic fractures which were stabilized by newly established bone substitution materials. Therefore, we recently established a fracture defect model in the distal metaphyseal area of the femur of osteoporotic rats [9-11]. We decided to use small animals in this first approach because of the shorter breeding cycles, easier and less expensive animal housing that allowed us to investigate several different bone substitution materials.…”

Section: Introductionmentioning

confidence: 99%

Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

et al. 2013

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Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing.

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A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures

Cited by 77 publications

References 35 publications

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

Biomaterials for enhancement of bone healing in osteoporotic fractures

Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

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