Proteomics and Metabolomics forIn SituMonitoring of Wound Healing

Abstract

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.

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

“…As discussed in the introduction, targeted and untargeted metabolomics approaches have only recently been applied to wound healing studies, but never in conjugation with a wound healing treatment [33, 34]. For this study, focus was placed on dysregulated metabolites that were classified based on their functional pathways, then these individual metabolites were targeted based on their connected wound healing processes and direct impact on the tissue of interest (Figure 5).…”

“…Recently, the need has been highlighted for high throughput biological techniques such as metabolomics, proteomics, and genomics to reveal new understanding of wound healing [32]. In a recent study, wound fluid samples were analyzed with proteomics and metabolomics to improve the understanding of bone defects and its connection to the biochemical mechanisms in the wound environment [33]. Another study used metabolomics profiling of diabetic and non-diabetic wounds in mice and identified key metabolites that were differentially regulated and could serve as future biomarkers [34].…”

A microbiome and metabolomic signature of phases of cutaneous healing identified by profiling sequential acute wounds of human skin: An exploratory study

“…The metabolome of wound healing has been understudied. Only two animal studies [9,10] and three human studies [11][12][13] have investigated the metabolic profile of cutaneous wounds at a single time-point using a metabolomics approach. In addition other "omic" technologies such as genomics have been utilised to assess the progressive changes in gene expression in wound healing over time [14,15].…”

Wound‐induced cell proliferation during animal regeneration

“…For example, although Raldh and NOS are upregulated in multiple species, different injury‐induced inputs may underlie this activation. Recent progress in high‐throughput proteomic and metabolomic approaches (Boser et al, ; Kalkhof et al, ; Looso et al, ; Natarajan, Ramakrishnan, Lakshmanan, Palakodeti, & Rangiah, ; J. Zhao et al, ) will enable the study of transcription‐independent processes launched upon injury. New regulators of IIHP are likely to be discovered with the advent of new technology, for example, development of fluorometric sensors for a wide array of small molecules as dNTPs and of high sensitivity H 2 O 2 sensors that enable more effective detection of diffusible molecules at very low concentrations (Mugoni, Camporeale, & Santoro, ; Sprenger & Nikolaev, ; Zheng, Peng, Jiang, Wang, & Xu, ).…”