Monitoring of the first stages of bone healing with microdialysis

Förster, Yvonne; Gao, Wenling; Demmrich, A.; Hempel, Ute; Hofbauer, Lorenz C.; Rammelt, Stefan

doi:10.3109/17453674.2013.769080

Cited by 11 publications

(16 citation statements)

References 25 publications

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“…Moreover proteins also adsorbed to it. As previously was determined, even low molecular weight proteins such as IL-6 (20.8 kDa) or TGF-beta 1 (12.8 kDa) were nearly completely retarded (recovery below 10%) by dialysis membranes with a cutoff of 100 kDa [13]. Anticipating that a significant percentage of the protein amount was adsorbed at the microdialysis catheter material, the catheters' tips were used to extract, enrich, and purify proteins directly from different tissue defects.…”

Section: Resultsmentioning

confidence: 99%

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Proteomics and Metabolomics forIn SituMonitoring of Wound Healing

Kalkhof

Förster

Schmidt

et al. 2014

BioMed Research International

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Wound healing of soft tissue and bone defects is a complex process in which cellular differentiation and adaption are regulated by internal and external factors, among them are many different proteins. In contrast to insights into the significance of various single proteins based on model systems, the knowledge about the processes at the actual site of wound healing is still limited. This is caused by a general lack of methods that allow sampling of extracellular factors, metabolites, and proteins in situ. Sampling of wound fluids in combination with proteomics and metabolomics is one of the promising approaches to gain comprehensive and time resolved data on effector molecules. Here, we describe an approach to sample metabolites by microdialysis and to extract proteins simultaneously by adsorption. With this approach it is possible (i) to collect, enrich, and purify proteins for a comprehensive proteome analysis; (ii) to detect more than 600 proteins in different defects including more than 100 secreted proteins, of which many proteins have previously been demonstrated to have diagnostic or predictive power for the wound healing state; and (iii) to combine continuous sampling of cytokines and metabolites and discontinuous sampling of larger proteins to gain complementary information of the same defect.

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Section: Resultsmentioning

confidence: 99%

“…Proteomics in combination with, for example, microdialysis has already been used to study fluids from a wide variety of different tissues such as skin [10], brain [11], liver [12], bone [13], and eye [14]. …”

Section: Introductionmentioning

confidence: 99%

Proteomics and Metabolomics forIn SituMonitoring of Wound Healing

Kalkhof

Förster

Schmidt

et al. 2014

BioMed Research International

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“…To circumvent this problem, osmotic agents such as Dextran-60 (~ 60 kDa) or -70 (~70 kDa) were being added at high concentrations (1 to 4% w/v). These agents have since been widely used in microdialysis sampling with 100 kDa MWCO membranes (Abrahamsson et al, 2012; Dabrosin, 2003; Dostalova et al, 2009; Dostálová et al, 2003; Farnebo et al, 2009; Förster et al, 2013; Hillman et al, 2005b; Hillman et al, 2006; Mellergard et al, 2008; Mellergård et al, 2011; Rosenbloom et al, 2006; Sjoegren and Anderson, 2009; Sjögren et al, 2012; Sjögren et al, 2002; von Grote et al, 2011; Waelgaard et al, 2008; Zhong et al, 2007). Our results show that Dextran-70, when allowed to enter the extracellular space, causes an intense inflammatory response.…”

Section: 0 Discussionmentioning

confidence: 99%

Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue

Keeler¹,

Durdik²,

Stenken³

2014

European Journal of Pharmaceutical Sciences

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Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100 kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer’s solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives.

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“…Concentrations were highest at 6 hr in the muscle and vessels at the fracture site (883 ± 53 and 1,932 ± 299 ng/ml, respectively), dropping significantly after this time point (Currie et al, ). A study using microdialysis in murine femoral osteotomies reported levels of 174 pg/ml in the first 8 hr of injury, peaking at 12–15 hr with an IL‐6 concentration of 344 pg/ml (Förster et al, ). Values dropped significantly after this time point.…”

Section: Cytokines and Growth Factor Content Of Fracture Haematomamentioning

confidence: 99%

The cytokines and micro‐environment of fracture haematoma: Current evidence

Walters

Pountos

Giannoudis

2017

J Tissue Eng Regen Med

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Fracture haematoma formation is the first and foremost important stage of fracture healing. It orchestrates the inflammatory and cellular processes leading to the formation of callus and the restoration of the continuity of the bone. Evidence suggests that blocking this initial stage could lead to an impairment of the overall bone healing process. This review aims to analyse the existing evidence of molecular contributions to bone healing within fracture haematoma and to determine the potential to modify the molecular response to fracture in the haematoma with the aim of improving union times. A comprehensive search of literature documenting fracture haematoma cytokine content was performed. Suitable papers according to prespecified criteria were identified and analysed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A total of 89 manuscripts formed the basis of this analysis. Low oxygen tension, high acidity, and high calcium characterised initially the fracture haematoma micro-environment. In addition, a number of cytokines have been measured with concentrations significantly higher than those found in peripheral circulation. Growth factors have also been isolated, with an observed increase in bone morphogenetic proteins, platelet-derived growth factor, and transforming growth factor. Although molecular modification of fracture haematoma has been attempted, more research is required to determine a suitable biological response modifier leading to therapeutic effects. The cytokine content of fracture haematoma gives insight into processes occurring in the initial stages of fracture healing. Manipulation of signalling molecules represents a promising pathway to target future therapies aiming to upregulate the osteogenesis.

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Monitoring of the first stages of bone healing with microdialysis

Cited by 11 publications

References 25 publications

Proteomics and Metabolomics forIn SituMonitoring of Wound Healing

Proteomics and Metabolomics forIn SituMonitoring of Wound Healing

Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue

The cytokines and micro‐environment of fracture haematoma: Current evidence

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