Quantitative assessment of angiogenesis and osteogenesis after transplantation of bone: Comparison of isograft and allograft bone in mice

Leunig, Michael; Tj, Demhartner; Sckell, Axel; Cr, Fraitzl; Gries, N.; Rk, Schenk; Ganz, Reinhold

doi:10.3109/17453679908997827

Cited by 23 publications

(13 citation statements)

References 18 publications

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“…Vascularity is essential for providing optimal blood supply to maintain survival of the osteogenic cells. The angiogenic response from the host is five to 10 times greater with fresh isograft compared to cryopreserved isograft in the subcutaneous bone graft transplantation model [52,53]. A reciprocal role of angiogenesis and osteogenesis in bone repair has been illustrated in several bone repair and regeneration models [28,87].…”

Section: Design Rationale and Outcome Evaluations For Tissue-engineermentioning

confidence: 90%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

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Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

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Section: Design Rationale and Outcome Evaluations For Tissue-engineermentioning

confidence: 90%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

206

169

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“…For the assessment of centerline velocity, white blood cells (WBCs) were stained in vivo with rhodamine 6G (2 mol/kg body wt iv, Sigma). Fluorescence was visualized with the aid of an excitation filter (530-560 nm), a dichroic mirror (580 nm), and a barrier filter (580 nm) and through epi-illumination by a mercury lamp (Atto Arc, Zeiss) (13). Velocity was calculated by measuring the distance covered by the WBC during one time frame (20 ms).…”

Section: Methodsmentioning

confidence: 99%

Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O₂ affinity

Contaldo¹,

Schramm²,

Wettstein³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O 2 affinity. Am J Physiol Heart Circ Physiol 285: H1140-H1147, 2003. First published May 8, 2003 10.1152/ ajpheart.00285.2003.-The aim of this study was to test the influence of oxygen affinity of Hb vesicles (HbVs) and level of blood exchange on the oxygenation in collateralized, ischemic, and hypoxic hamster flap tissue during normovolemic hemodilution. Microhemodynamics were investigated with intravital microscopy. Tissue PO 2 was measured with Clarktype microprobes. HbVs with a P 50 of 15 mmHg (HbV15) and 30 mmHg (HbV30) were suspended in 6% Dextran 70 (Dx70). The Hb concentration of the solutions was 7.5 g/dl. A stepwise replacement of 15%, 30%, and 50% of total blood volume was performed, which resulted in a gradual decrease in total Hb concentration. In the ischemic tissue, hemodilution led to an increase in microvascular blood flow to maximally 141-166% of baseline in all groups (median; P Ͻ 0.01 vs. baseline, not significant between groups). Oxygen tension was transiently raised to 121 Ϯ 17% after the 30% blood exchange with Dx70 (P Ͻ 0.05), whereas it was increased after each step of hemodilution with HbV15-Dx70 and HbV30-Dx70, reaching 217 Ϯ 67% (P Ͻ 0.01) and 164 Ϯ 33% (P Ͻ 0.01 vs. baseline and other groups), respectively, after the 50% blood exchange. We conclude that despite a decrease in total Hb concentration, the oxygenation in the ischemic, hypoxic tissue could be improved with increasing blood exchange with HbV solutions. Furthermore, better oxygenation was obtained with the left-shifted HbVs. blood substitutes; artificial red blood cells; microhemodynamics; hypoxia; collateral circulation MAINTAINING ADEQUATE OXYGENATION is crucial for functional recovery and survival of cerebral, myocardial, mesenteric, or peripheral tissues rendered ischemic due to acute obstruction of their anatomic blood supply. In this scenario, oxygenation is determined by the amount of oxygen that is transported into the infarcted tissue via a collateral vasculature as well as by the potential of the oxygen carrier to deliver oxygen to this tissue.Oxygenation and survival of ischemic myocardial (7, 19), cerebral (3, 18, 29), and peripheral tissues (2) could successfully be improved after the infusion of solutions containing artificial oxygen carriers, such as perfluorocarbons and chemically modified Hbs. These solutions have initially been developed with the scope of reducing the need of allogeneic blood transfusions, and at least four compounds are currently in advanced clinical trials to evaluate their potential as red blood cell (RBC) substitutes in blood loss (1, 10).In a recent study (6), we were able to demonstrate that hypoxia in ischemic, collateralized hamster flap tissue was attenuated by a 50% blood exchange with a solution containing Hb vesicles (HbVs) suspended in 6% Dextran 70 (Dx70). The effect was associated with an increased capacity to transport oxygen to the ischemic tissue...

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“…The application of intravital microscopy has proven to be a successful approach to investigate microcirculatory properties in various tissues at a high spatial resolution [1, 4,14,21,31,48,57,62].…”

Section: Introductionmentioning

confidence: 99%

Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt

Schaefer

Wolfram

et al. 2005

Journal Orthopaedic Research

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Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis.Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIS) in femoral bone tissue of c57-black mice ( n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested.Results: Microvascular permeability and LEIS showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion:The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis.

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Quantitative assessment of angiogenesis and osteogenesis after transplantation of bone: Comparison of isograft and allograft bone in mice

Cited by 23 publications

References 18 publications

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O₂ affinity

Femur window—a new approach to microcirculation of living bone in situ

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Quantitative assessment of angiogenesis and osteogenesis after transplantation of bone: Comparison of isograft and allograft bone in mice

Cited by 23 publications

References 18 publications

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O2 affinity

Femur window—a new approach to microcirculation of living bone in situ

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Product

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Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O₂ affinity