Repair of segmental bone defects in the rat: an experimental model of human fracture healing∗∗Dr. Kashinath Patil, Professor of Biostatistics, Department of Preventive and Societal Medicine, University of Nebraska Medical Center, has assisted us for the past 16 years in the statistical design of the experiments and data analysis. He passed away on December 24, 1998 after a period of illness. We dedicate this manuscript to his memory.

Chakkalakal, Dennis A.; Strates, Basil S.; Mashoof, A. Allen; Garvin, Kevin L.; Novak, Jerzy R.; Fritz, Edward D.; Mollner, Teresa J.; McGuire, Michael H.

doi:10.1016/s8756-3282(99)00167-2

Cited by 55 publications

(6 citation statements)

References 17 publications

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“…A multitude of studies have shown that EO can be induced by combining biomaterials with progenitor cells 11 , 49 , by progenitor cells in combination with organic ECM components 50 , 51 , by pre-differentiated cells 8 , 52 , platelet-rich plasma 53 , growth factors, and demineralized bone matrix 54 . Progenitor cells bear an inherent potential for tissue genesis and were shown to induce ectopic EO 20 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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. The unsolved clinical challenge to regenerate large bone defects has brought endochondral ossification into discussion as an alternative approach for bone healing. However, a biomaterial strategy for the regeneration of large bone defects via endochondral ossification is missing. 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. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing. This might motivate future strategies for biomaterial-based tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…Animal fracture models have been extensively used for decades in preclinical orthopedics research 24,25 with rats being the most popular, 26 to establish strategies to further understand the physiology of bone healing and to improve treatment outcomes. Traditionally, the physical impact for orthopedic trauma models was generated using a falling weight or bending pliers 5,8 .…”

Section: Discussionmentioning

confidence: 99%

High‐energy open‐fracture model with initial experience of fluorescence‐guided bone perfusion assessment

Demidov

Clark

Streeter

et al. 2022

Journal Orthopaedic Research

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High-energy orthopedic injuries cause severe damage to soft tissues and are prone to infection and healing complications, making them a challenge to manage. Further research is facilitated by a clinically relevant animal model with commensurate fracture severity and soft-tissue damage, allowing evaluation of novel treatment options and techniques. Here we report a reproducible, robust, and clinically relevant animal model of high-energy trauma with extensive softtissue damage, based on compressed air-driven membrane rupture as the blast wave source. As proof-of-principle showing the reproducibility of the injury, we evaluate changes in tissue and bone perfusion for a range of different tibia fracture severities, using dynamic contrast-enhanced fluorescence imaging and microcomputed tomography. We demonstrate that fluorescence tracer temporal profiles for skin, femoral vein, fractured bone, and paw reflect the increasing impact of more powerful blasts causing a range of Gustilo grade I-III injuries. The maximum fluorescence intensity of distal tibial bone following 0.1 mg/kg intravenous indocyanine green injection decreased by 35% (p < 0.01), 75%(p < 0.001), and 87% (p < 0.001), following grade I, II, and III injuries, respectively, compared to uninjured bone. Other kinetic parameters of bone and soft tissue perfusion extracted from series of fluorescence images for each animal also showed an association with severity of trauma. In addition, the time-intensity profile of fluorescence showed marked differences in wash-in and wash-out patterns for different injury severities and anatomical locations. This reliable and realistic high-energy trauma model opens new research avenues to better understand infection and treatment strategies. Level of evidence: Level III;

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“…Low union rates are caused with use of cortical grafts or syngeneic grafts, but when cancellous bone is used the union rates are always around 90% 37131922. The union rates with DBM are also variable, being between 60%–100% 13781322–24. Although the differences in union rates are believed to be related to the type of manufacturing process of DBM, this has not been definitely established because of difficulties in quantitative measurement of the efficiency of demineralized bone 25.…”

Section: Discussionmentioning

confidence: 99%

“…One of these is demineralized bone matrix (DBM), which is a proven material for bone grafting procedures. It contains collagen as well as noncollagenous proteins like bone morphogenetic proteins (BMP), transforming growth factor-α (TGF-α), and fibroblast growth factor (FGF) 36. The osteoinductive properties of DBM causes differentiation of mesenchymal stem cells to the osteoblastic pathway, chemotaxis of osteoblastic precursor cells to the grafted area, and induction of osteoblast function in the grafted area 7–13.…”

Section: Introductionmentioning

confidence: 99%

Repair of long bone defects with demineralized bone matrix and autogenous bone composite

Ozdemir

Kır

2011

IJOO

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Background:Repair of diaphyseal bone defects is a challenging problem for orthopedic surgeons. In large bone defects the quantity of harvested autogenous bone may not be sufficient to fill the gap and then the use of synthetic or allogenic grafts along with autogenous bone becomes mandatory to achieve compact filling. Finding the optimal graft mixture for treatment of large diaphyseal defects is an important goal in contemporary orthopedics and this was the main focus of this study. The aim of this study is to investigate the efficacy of demineralized bone matrix (DBM) and autogenous cancellous bone (ACB) graft composite in a rabbit bilateral ulna segmental defect model.Materials and Methods:Twenty-seven adult female rabbits were divided into five groups. A two-centimeter piece of long bone on the midshaft of the ulna was osteotomized and removed from the rabbits’ forearms. In group 1 (n=7) the defects were treated with ACB, in group 2 (n=7) with DBM, and in group 3 (n=7) with ACB and DBM in the ratio of 1:1. Groups 4 and 5, with three rabbits in each group, were the negative and positive controls, respectively. Twelve weeks after implantation the rabbits were sacrificed and union was evaluated with radiograph (Faxitron), dual-energy x-ray absorptiometry (DEXA), and histological methods (decalcified sectioning).Results:Union rates and the volume of new bone in the different groups were as follows: group 1 - 92.8% union and 78.6% new bone; group 2 - 72.2% union and 63.6% new bone; and group 3 - 100% union and 100% new bone. DEXA results (bone mineral density [BMD]) were as follows: group 1 - 0.164 g/cm2, group 2 - 0.138 g/cm2, and group 3 - 0.194 g/cm2.Conclusions:DBM serves as a graft extender or enhancer for autogenous graft and decreases the need of autogenous bone graft in the treatment of bone defects. In this study, the DBM and ACB composite facilitated the healing process. The union rate was better with the combination than with the use of any one of these grafts alone.

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Cited by 55 publications

References 17 publications

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

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

High‐energy open‐fracture model with initial experience of fluorescence‐guided bone perfusion assessment

Repair of long bone defects with demineralized bone matrix and autogenous bone composite

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