Growth and transplantation of a custom vascularised bone graft in a man

Warnke, Patrick H.; Springer, Ingo N.; Wiltfang, Jens; Açil, Yahya; Eufinger, H.; Wehmöller, M.; Russo, Paul; Bolte, Hendrik; Sherry, Eugene; Behrens, Eleonore; Terheyden, Hendrik

doi:10.1016/s0140-6736(04)16935-3

Cited by 643 publications

(450 citation statements)

References 11 publications

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“…However, the AV loop model avoids the donor site morbidity of a whole latissimus dorsi muscle, which was taken into account for the first clinical attempt to create de novo axially vascularized, and thus transplantable, bone tissue (Warnke et al, 2004). Another important feature of this AV loop-based construct would be the degree of vascularization prior to transplanting it to the site of defect.…”

Section: Discussionmentioning

confidence: 99%

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Beier¹,

Horch²,

Heß

et al. 2010

J Tissue Eng Regen Med

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Vascularization still remains an obstacle to engineering of bone tissue with clinically relevant dimensions. Our aim was to induce axial vascularization in a large volume of a clinically approved biphasic calcium phosphate ceramic by transferring the arteriovenous (AV) loop approach to a large animal model. HA/β-TCP granula were mixed with fibrin gel for a total volume of 16 cm 3 , followed by incorporation into an isolation chamber together with an AV loop. The chambers were implanted into the groins of merino sheep and the development of vascularization was monitored by sequential non-invasive magnetic resonance imaging (MRI). The chambers were explanted after 6 and 12 weeks, the pedicle was perfused with contrast agent and specimens were subjected to micro-computed tomography (µ-CT) scan and histological analysis. Sequential MRI demonstrated a significantly increased perfusion in the HA/β-TCP matrices over time. Micro-CT scans and histology confirmed successful axial vascularization of HA/β-TCP constructs. This study demonstrates, for the first time, successful axial vascularization of a clinically approved bone substitute with a significant volume in a large animal model by means of a microsurgically created AV loop, thus paving the way for the first microsurgical transplantation of a tissue-engineered, axially vascularized bone with clinically relevant dimensions.

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Section: Discussionmentioning

confidence: 99%

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Beier¹,

Horch²,

Heß

et al. 2010

J Tissue Eng Regen Med

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“…24,25 BMPs have been shown to be promising; clinical applications of BMP-2 and BMP-7 are underway. [13][14][15][16][17][18][19][20][21][22]26 Further investigation of their mechanisms of action and formulations are required to optimize their osteopromotive effectiveness. The results of our study showed that the combination of BMP-2, BMP-5, and BMP-6 stimulates murine osteoblasts in vitro, but not the generation of osteoclasts.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic proteins 2, 5, and 6 in combination stimulate osteoblasts but not osteoclasts in vitro

Wutzl

Rauner

Seemann

et al. 2010

Journal Orthopaedic Research

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Bone regeneration is required for fracture healing. Various procedures have been used to promote osteogenesis with bone morphogenetic proteins (BMPs). We assessed the effects of BMP-2, BMP-5, and BMP-6 in isolated and combined use on the generation of osteoblasts and osteoclasts by comparing the osteoclastic potency of each on osteoclasts of primary murine bone marrow cells. Subsequently, cells were stained for tartrate-resistant acid phosphatase, and real time PCR analysis of receptor activator of NK B ligand and osteoprotegerin was conducted. The same combination of BMPs was used to assess their potential to enhance osteoblasts, employing a mineralization assay and real-time PCR analysis of collagen type-1, runx2, and osterix. While BMP-2 alone and the combination of BMP-2 and BMP-5 significantly enhanced osteoclastogenesis, BMP-2, BMP-5, and BMP-6 in combination did not have additional effects. However, the combined use of BMP-2, BMP-5, and BMP-6 had an additive effect on matrix mineralization and osterix expression in osteoblasts. Our study shows that the combination of BMP-2, BMP-5, and BMP-6 stimulates osteoblasts but not osteoclastogenesis. Keywords: BMP-2; BMP-5; BMP-6; osteoclast; osteoblast Bone undergoes continuous remodeling and is one of the few organs that retains its potential for regeneration in adult life. 1,2 Bone regeneration results from resorption and formation, subject to the generation and activity of osteoclasts and osteoblasts. This balance is regulated by systemic hormones and local factors such as growth factors, cytokines, and prostaglandins.Bone morphogenetic proteins (BMPs) have become interesting therapeutic targets to promote bone regeneration. In vitro studies showed that BMPs regulate cell proliferation, differentiation, and apoptosis in a variety of cell types. BMPs induce the differentiation of mesenchymal cells into osteogenic cells and enhance the function of mature osteoblasts, 3−6 establishing an osteogenic hierarchical model in which BMP-2 and BMP-6 have the greatest effects in inducing osteoblast differentiation. 7−10 In addition, some BMPs stimulate osteoclast formation. 8,11 Hence, BMPs act on osteoclastic bone resorption and cartilage and bone formation, thereby spanning all process of bone remodeling. 12 Recombinant forms of BMPs, especially BMP-2 and BMP-7, induce bone formation in vivo and both were tested in clinical trials. 13−22 The data suggest that BMP-induced bone formation is at least equivalent to autogenous bone grafting when used in alveolar bone grafting, spinal fusion, and tibia non-union.

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“…It would be better if it is possible to create the correct environment in vivo and use the patient as their own bioreactor. This has been achieved by the recreation of a mandible with autologous bone marrow, a bone mineral carrier and BMP7 inside a computer aided design (CAD) scaffold which was implanted in the patient's latissimus dorsi for 7 weeks before locating in the correct position (Warnke et al, 2005). Perhaps one useful way forward for disc and meniscus tissue engineering is to understand better the natural repair processes that exist, however limited.…”

Section: Tissue Engineeringmentioning

confidence: 99%

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

Roberts¹,

Turner²,

Evans³

2016

Comprehensive Biotechnology

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Synopsis/AbstractThe intervertebral disc in the spine and the meniscus in the knee are two fibrocartilaginous tissues which commonly are injured or become degenerate, causing significant clinical problems. The principals of tissue engineering, which are applicable elsewhere in the body, hold true for the disc and meniscus. Whilst there are some similarities with articular cartilage in terms of the molecules present, these fibrocartilages have their own peculiarities, some of which can be quite challenging. Following a description of the structure and anatomy of the disc and meniscus and the current clinical treatments, the different strategies for biological repair are described focusing particularly on cell therapy. The types of cells and scaffolds being investigated and how these can be modified are discussed.

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Growth and transplantation of a custom vascularised bone graft in a man

Cited by 643 publications

References 11 publications

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Bone morphogenetic proteins 2, 5, and 6 in combination stimulate osteoblasts but not osteoclasts in vitro

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

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