Optimization of an Ex-Vivo Human Skin/Vein Model for Long-Term Wound Healing Studies: Ground Preparatory Activities for the 'Suture in Space' Experiment Onboard the International Space Station

This study is preliminary to an experiment to be performed onboard the International Space Station (ISS) and on Earth to investigate how low gravity influences the healing of sutured human skin and vein wounds. Its objective was to ascertain whether these tissue explants could be maintained to be viable ex vivo for long periods of time, mimicking the experimental conditions onboard the ISS. We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation. The results show that the human skin and vein specimens remained viable for more than 4 weeks, with no substantial signs of damage in their tissues and cells. As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes

Suture in Space: Preparation of an Experiment on the Healing of Sutured Wounds on Board the ISS

Wound healing (WH) is a process strictly regulated and highly conserved throughout evolution because it is indispensable for surviving injuries. On Earth WH has been studied in depth, nevertheless the role of mechanical factors in regulating the process and the mechanisms that, in adult mammals, lead to scarring instead of tissue regeneration are not well understood. In weightlessness WH has been poorly studied, and the effect of loading/unloading on the healing mechanisms is quite completely unknown. Preliminary studies showed microgravity-induced alterations in mechanisms underlying tissue repair. The implementation of procedures and tools to manage emergency surgery, trauma, serious burns, wounds and sutures is mandatory for future human deep space exploration missions at distances which are incompatible with medical evacuation to Earth. Therefore, studies on WH in weightlessness are needed and they are also an unique opportunity for understanding healing mechanisms still not completely known. The Suture in Space experiment, which will be performed on board the International Space Station (ISS), was selected by ESA (ESA-AO-ILSRA-2014) and supported by ASI in its development phase. It aims to study in weightlessness the behavior and healing of ex vivo sutured wound models prepared from skin and blood vessels biopsies derived from plastic and vascular surgery in healthy subjects. The experiment preparation required intense research activity on ground in order to: i) standardize procedures for collection of biopsies, model preparation, tissue culturing and monitoring, postflight analysis of samples; ii) define the requirements for hardware development. To ensure tissue viability throughout the in-flight experiment (4 weeks), we studied and developed a new tissue culture technique based on enriched culture media and a device able to model the physiological mechanical tension in the tissues and monitor its changes during WH, thus enabling the study of suture mechanical properties. The culture technique and WH models developed for the Suture in Space experiment can be applied to study: i) mechanical properties of tissues, tissue constructs, wounds and sutures in different loading conditions; ii) the role of gravity in tissue repair; iii) the relationship between biochemical and mechanical factors in repair mechanisms; iv) the influence of mechanical factors on scar quality; v) the effectiveness of treatments promoting WH, when applied in different loading conditions. The results of the experiment are expected to help in defining: i) strategies to manage wounds and promote healing in Space and on Earth; ii) suture techniques and materials to be used in space environment

Suture in Space: Preparation of an Experiment on the Healing of Sutured Wounds on Board the ISS

Wound healing (WH) is a process strictly regulated and highly conserved throughout evolution because it is indispensable for surviving injuries. On Earth WH has been studied in depth, nevertheless the role of mechanical factors in regulating the process and the mechanisms that, in adult mammals, lead to scarring instead of tissue regeneration are not well understood. In weightlessness WH has been poorly studied, and the effect of loading/unloading on the healing mechanisms is quite completely unknown. Preliminary studies showed microgravity-induced alterations in mechanisms underlying tissue repair. The implementation of procedures and tools to manage emergency surgery, trauma, serious burns, wounds and sutures is mandatory for future human deep space exploration missions at distances which are incompatible with medical evacuation to Earth. Therefore, studies on WH in weightlessness are needed and they are also an unique opportunity for understanding healing mechanisms still not completely known. The Suture in Space experiment, which will be performed on board the International Space Station (ISS), was selected by ESA (ESA-AO-ILSRA-2014) and supported by ASI in its development phase. It aims to study in weightlessness the behavior and healing of ex vivo sutured wound models prepared from skin and blood vessels biopsies derived from plastic and vascular surgery in healthy subjects. The experiment preparation required intense research activity on ground in order to: i) standardize procedures for collection of biopsies, model preparation, tissue culturing and monitoring, postflight analysis of samples; ii) define the requirements for hardware development. To ensure tissue viability throughout the in-flight experiment (4 weeks), we studied and developed a new tissue culture technique based on enriched culture media and a device able to model the physiological mechanical tension in the tissues and monitor its changes during WH, thus enabling the study of suture mechanical properties. The culture technique and WH models developed for the Suture in Space experiment can be applied to study: i) mechanical properties of tissues, tissue constructs, wounds and sutures in different loading conditions; ii) the role of gravity in tissue repair; iii) the relationship between biochemical and mechanical factors in repair mechanisms; iv) the influence of mechanical factors on scar quality; v) the effectiveness of treatments promoting WH, when applied in different loading conditions. The results of the experiment are expected to help in defining: i) strategies to manage wounds and promote healing in Space and on Earth; ii) suture techniques and materials to be used in space environment