Mechanical induction of critically delayed bone healing in sheep: Radiological and biomechanical results

Schell, Hanna; Thompson, Mark S.; Bail, Hermann Josef; Hoffmann, Jan‐Erik; Schill, Alexander; Duda, Georg N.; Lienau, Jasmin

doi:10.1016/j.jbiomech.2008.06.038

Cited by 63 publications

(60 citation statements)

References 26 publications

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“…The time course of fracture healing in our experiments corresponds well with that of previously published ovine models [9][10][11]. In fact, both for simple osteotomy models as well as for the multi-fragmentary fracture model by Baumgaertel, similar stiffness and strength values at comparable time points have been reported [12].…”

Section: Discussionsupporting

confidence: 88%

A New Model to Study Healing of a Complex Femur Fracture with Concurrent Soft Tissue Injury in Sheep

Wullschleger¹,

Steck²,

Matthys³

et al. 2013

OJO

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High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep's femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed increasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.

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Section: Discussionsupporting

confidence: 88%

A New Model to Study Healing of a Complex Femur Fracture with Concurrent Soft Tissue Injury in Sheep

Wullschleger¹,

Steck²,

Matthys³

et al. 2013

OJO

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“…Group II (n ¼ 65) was treated with a mechanically critical external fixator allowing free rotation with a highly stiff stainless-steel tube set in two tapered roller bearings and producing a distinctly delayed healing. 17 All animal experiments were carried out according to the policies and principles established by the Animal Welfare Act, the NIH Guide for Care and Use of Laboratory Animals, and the national animal welfare guidelines. The study was approved by the local legal representative (LAGeSo, Berlin: G0127/07, G0172/04, G0224/01).…”

Section: Methods Animalsmentioning

confidence: 99%

Differential regulation of blood vessel formation between standard and delayed bone healing

Lienau

Schmidt‐Bleek

Peters

et al. 2009

Journal Orthopaedic Research

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122

120

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Blood vessel formation is a prerequisite for bone healing. In this study, we tested the hypothesis that a delay in bone healing is associated with an altered regulation of blood vessel formation. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a highly rotationally unstable one leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of vWF, an endothelial cell marker, and of several molecules related to blood vessel formation were studied by qPCR. Furthermore, histology was performed on fracture hematoma and callus sections. Histologically, the first blood vessels were detected at day 7 in both groups. mRNA expression levels of vWF, Ang1, Ang2, VEGF, CYR61, FGF2, MMP2, and TIMP1 were distinctly lower in the delayed compared to the standard healing group at several time points. Based on differential expression patterns, days 7 and 21 postoperatively were revealed to be essential time points for vascularization of the ovine fracture callus. This work demonstrates for the first time a differential regulation of blood vessel formation between standard and mechanically induced delayed healing in a sheep osteotomy model. ß

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“…The rigid mono-lateral external fixator consisted of six Ø 5-mm Schanz screws and two Ø 10-mm steel rods (Synthes, Germany) (Schell et al 2008). The critical mono-lateral external fixator was designed to allow free rotation with a highly stiff stainless-steel tube set in two tapered roller bearings and was mounted on six Ø 5-mm Schanz screws (Schell et al 2008).…”

Section: External Fixatorsmentioning

confidence: 99%

“…We tested this hypothesis in an ovine osteotomy healing model using two external fixators leading to either uneventful or distinctly delayed healing (Schell et al 2008). The aim was to compare the immune cell composition in the osteotomy hematoma and the adjacent bone marrow as well as the expression pattern of relevant angiogenic factors in the hematoma and the adjacent periosteum 60 h after surgery.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory phase of bone healing initiates the regenerative healing cascade

et al. 2011

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Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced impaired/delayed bone healing group. In the impaired/delayed healing group, significantly higher T cell percentages were present in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group. This was mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory processes. The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor. This indicates a deferred revascularization of the injured area due to ongoing pro-inflammatory processes in the delayed healing group. Results from this study suggest that there are unfavorable immune cells and factors participating in the initial healing phase. In conclusion, identifying beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable factors.

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Mechanical induction of critically delayed bone healing in sheep: Radiological and biomechanical results

Cited by 63 publications

References 26 publications

A New Model to Study Healing of a Complex Femur Fracture with Concurrent Soft Tissue Injury in Sheep

A New Model to Study Healing of a Complex Femur Fracture with Concurrent Soft Tissue Injury in Sheep

Differential regulation of blood vessel formation between standard and delayed bone healing

Inflammatory phase of bone healing initiates the regenerative healing cascade

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