New Approaches in the Treatment of Critical‐Size Segmental Defects in Long Bones

Gugala, Zbigniew; Lindsey, Ronald W.; Gogolewski, Sylwester

doi:10.1002/masy.200750722

“…Critical-size defects in animal models are defined as ''the smallest size intraosseous wound in a particular bone and species of animal that will not heal spontaneously during the lifetime of the animal'' 27,67 or a defect with <10% bone regeneration over the animal's lifetime. 27 Surgically created critical defects are a gap in length >2.25 times the diameter of the affected bone 26,46 or large cylindrical defects in femoral condyles or tibial metaphysis. Rats, rabbits, and increasingly small ruminants are used in defect models.…”

Section: Large Bone Defects and Nonunionsmentioning

confidence: 99%

Animal Models for Evaluation of Bone Implants and Devices

Wancket

¹

2015

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Bone implants and devices are a rapidly growing field within biomedical research, and implants have the potential to significantly improve human and animal health. Animal models play a key role in initial product development and are important components of nonclinical data included in applications for regulatory approval. Pathologists are increasingly being asked to evaluate these models at the initial developmental and nonclinical biocompatibility testing stages, and it is important to understand the relative merits and deficiencies of various species when evaluating a new material or device. This article summarizes characteristics of the most commonly used species in studies of bone implant materials, including detailed information about the relevance of a particular model to human bone physiology and pathology. Species reviewed include mice, rats, rabbits, guinea pigs, dogs, sheep, goats, and nonhuman primates. Ultimately, a comprehensive understanding of the benefits and limitations of different model species will aid in rigorously evaluating a novel bone implant material or device.

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“…It is based on osteotomies combined with bone distraction and is successfully applied to treat large bone defects, infected non-unions and limb length discrepancy (Cierny and Zorn 1994 ) . However, this approach is long-lasting, inconvenient for the patient (Goldstrohm et al 1984 ;Ilizarov 1989 ) and recurrent pin track infections and pin loosening are common complications (Lindsey et al 2006 ;Gugala et al 2007 ) .…”

Section: Clinical Backgroundmentioning

confidence: 98%

Preclinical Animal Models for Segmental Bone Defect Research and Tissue Engineering

Reichert¹,

Berner²,

Saifzadeh³

et al. 2013

Regenerative Medicine

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Commonly applied therapies to achieve bone reconstruction or function are restricted to the transplantation of autografts and allografts, or the implantation of metal devices or ceramic-based implants. Bone grafts generally possess osteoconductive and osteoinductive properties. They are, however, limited in access and availability and harvest is associated with donor site morbidity, hemorrhage, risk of infection, insuf fi cient transplant integration, and graft devitalisation. As a result, recent research focuses on the development of alternative therapeutic concepts. Available literature indicates that bone regeneration has become a focus area in the fi eld of tissue engineering. Hence, a considerable number of research groups and commercial entities work on the development of tissue engineered constructs to aid bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and cost-intensive. Approval requires both comprehensive in vitro and in vivo studies necessitating the utilisation of large preclinical animal models. Consequently, to allow comparison between different studies and their outcomes, it is essential to standardize animal models, fi xation devices, surgical procedures and methods of taking measurements to produce reliable data pools as a base for further research directions. The following chapter reviews animal models of the weight-bearing lower extremity utilized in the fi eld, which include representations of fracture-healing, segmental bone defects, and fracture non-unions.

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“…Nevertheless, it has been described as a segmental bone defi ciency exceeding 2-2.5 times the diameter of the affected bone (Lindsey et al 2006 ;Gugala et al 2007 ). However, defect healing also depends on the species' phylogenetic scale, anatomic defect location, associated soft tissue, and biomechanical conditions in the affected limb as well as age, metabolic and systemic conditions, and related co-morbidities (Lindsey et al 2006 ;Rimondini et al 2005 ).…”

Section: Pre-clinical Evaluation In Large Animal Modelsmentioning

confidence: 99%

“…It is successfully applied to treat large bone defects, infected non-unions and limb length discrepancy (Cierny and Zorn 1994 ). The procedure is, however, longlasting, inconvenient for the patient (Goldstrohm et al 1984 ;Ilizarov 1989 ) and recurrent pin track infections and pin loosening are common complications (Lindsey et al 2006 ;Gugala et al 2007 ).To avoid the limitations related to current standard treatments, research interest has focused on bone graft substitutes, and the concept of tissue engineering has Fig. 9.1 Autologous, cancellous bone graft ( a ) harvested from the iliac crest ( b ) was used to reconstruct a 3 cm critical sized defect in an ovine tibia ( c , d ) Defects were stabilized with a 4.5 mm broad dynamic compression plate (Synthes).…”

mentioning

confidence: 99%

Bone

Reichert¹,

Nöth²,

Berner³

et al. 2016

Regenerative Medicine - From Protocol to Patient

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Commonly applied therapies to achieve bone reconstruction or function are restricted to the transplantation of autografts and allografts, or the implantation of metal devices or ceramic-based implants. Bone grafts generally possess osteoconductive and osteoinductive properties. They are, however, limited in access and availability, and harvest is associated with donor site morbidity, hemorrhage, risk of infection, insuffi cient transplant integration, and graft devitalisation. Research therefore focuses on alternative therapeutic concepts such as tissue engineering to aid bone regeneration. However, bench to bedside translations are infrequent as the process towards approval by regulatory bodies is protracted and costly. Approval requires both comprehensive in vitro and in vivo studies necessitating the utilization of well-standardized large preclinical animal models, fi xation devices, surgical procedures and methods of taking measurements. Only then reliable data pools can be generated which consecutively serve as a base for further research directions. The following chapter gives insight into bone morphology and physiology, and describes the clinical background necessitating research for alternative treatments. Furthermore, basic principles of bone tissue engineering are introduced as well as key points to consider when discussing preclinical animal models. Finally, successfully translated bone regeneration concepts are summarized. Keywords Bone Morphology and PhysiologyBone is a complex, constantly altering tissue and consists of cancellous and cortical bone. The specifi c architecture of bone allows the skeleton to fulfi l its mechanical functions. In adults, cortical bone accounts for 80 % of the total bone mass. It responds slowly to changes in loads and aids to protect organs, provides levers for movement, and (together with cancellous bone) stores minerals. Cancellous bone is found interiorly and comprises of a trabecular network that reduces organ weight and provides space for blood vessels and marrow. Cancellous bone has a large surface area per unit volume and a greate rate of metabolic activity. The external surface of bone is covered by periosteum (Hutmacher and Sittinger 2003 ).Specifi c collagen fi bres (Sharpey) connect periosteum and bone. These fi bres penetrate the cortex at sites exposed to high tensile forces. The periosteum comprises of an external, fi brous layer (collagenous and reticular fi bres) and an inner, proliferative layer (cambium). The cambium layer hosts osteoblasts and osteoprogenitor cells. It is capable of lamellar bone apposition and of forming primary, woven bone after a fracture. The outer fi brous layer provides elasticity and fl exibility facilitating the insertion of tendons, ligaments and muscles.Bone has a rich vascular supply receiving 10-20 % of the cardiac output. In long bones, one or two principal diaphyseal nutrient arteries represent the most important supply of arterial blood. These arteries pass obliquely through the cortical bone and divide into a...

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New Approaches in the Treatment of Critical‐Size Segmental Defects in Long Bones

Cited by 84 publications

References 10 publications

Animal Models for Evaluation of Bone Implants and Devices

Animal Models for Evaluation of Bone Implants and Devices

Preclinical Animal Models for Segmental Bone Defect Research and Tissue Engineering

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