Fibroblast matrix implants-a better alternative for incisional hernia repair?

The standard surgical procedure for abdominal hernia repair with conventional prosthetic mesh still results in a high recurrence rate. In the present study, we propose a fibroblast matrix implant (FMI), which is a three-dimensional (3D) poly-L-lactic acid scaffold coated with collagen (matrix) and seeded with fibroblasts, as an alternative mesh for hernia repair. The matrix was seeded with fibroblasts (cellularized) and treated with a conditioned medium (CM) of human Umbilical Cord Mesenchymal Stem Cells (hUC-MSC). Fibroblast proliferation and function were assessed and compared between treated with CM hUC-MSC and untreated group, 24 h after seeding onto the matrix (n= 3). To study the matricesin vivo,the hernia was surgically created on male Sprague Dawley rats and repaired with four different grafts (n= 3), including a commercial mesh (mesh group), a matrix without cells (cell-free group), a matrix seeded with fibroblasts (FMI group), and a matrix seeded with fibroblasts and cultured in medium treated with 1% CM hUC-MSC (FMI-CM group).In vitroexamination showed that the fibroblasts' proliferation on the matrices (treated group) did not differ significantly compared to the untreated group. CM hUC-MSC was able to promote the collagen synthesis of the fibroblasts, resulting in a higher collagen concentration compared to the untreated group. Furthermore, thein vivostudy showed that the matrices allowed fibroblast growth and supported cell functionality for at least 1 month after implantation. The highest number of fibroblasts was observed in the FMI group at the 14 d endpoint, but at the 28 d endpoint, the FMI-CM group had the highest. Collagen deposition area and neovascularization at the implantation site were observed in all groups without any significant difference between the groups. FMI combined with CM hUC-MSC may serve as a better option for hernia repair, providing additional reinforcement which in turn should reduce hernia recurrence.

Wound healing potential of human umbilical cord mesenchymal stem cell conditioned medium: An in vitro and in vivo study in diabetes-induced rats.

BACKGROUND AND AIM: Human umbilical cord mesenchymal stem cells (hUC-MSCs) and its conditioned medium (CM) promote wound healing. This study investigated the wound healing potential of hUC-MSC CM in vitro and in vivo using diabetic animal models. MATERIALS AND METHODS: The CM from hUC-MSC CM prepared under hypoxic conditions (hypoxic hUC-MSC) was evaluated for stimulating rat fibroblast growth, collagen production (in vitro), and wound healing in animal models (in vivo). An excision wound on the dorsal side of the diabetes-induced rats was established, and the rats were randomly divided into non-treatment, antibiotic, and hypoxic hUC-MSC CM groups. The cell number of fibroblasts and collagen secretion was evaluated and compared among the groups in an in vitro study. By contrast, wound size reduction, width of re-epithelialization, and the collagen formation area were assessed and compared among the groups in an in vivo study. RESULTS: CM under hypoxic conditions contained a higher concentration of wound healing-related growth factors. Hypoxic hUC-MSC CM could facilitate fibroblast cell growth and collagen synthesis, although not significant compared with the control group. Re-epithelialization and collagen production were higher in the hUC-MSC CM group than in the antibiotic and non-treatment groups. CONCLUSION: Hypoxic hUC-MSC CM possessed more positive effects on the wound healing process based on re-epithelialization and collagen formation than antibiotic treatment did.

Hepatocyte and Islet Cell Cotransplantation on Poly-L-Lactide Matrix for the Treatment of Liver Cirrhosis.

The human autologous hepatocyte matrix implant is a promising alternative procedure to counter liver damage. We assessed the outcome of human hepatocytes isolation from cirrhotic liver compared to the clinical and histological scores of disease severity. A total of 11 patients with various clinical scores (CTP and MELD) and histological score (Metavir, fibrosis) of liver cirrhosis were included in the hepatocyte matrix implant clinical phase I study. The liver segment and pancreatic tissue were harvested from each patient, and hepatocytes and cells of islets of Langerhans were isolated. The freshly isolated human hepatocytes were coseeded with the islet cells onto poly(l-lactic acid) (PLLA) scaffolds, cultured, and transplanted back into the patient. Human hepatocytes were isolated from 11 cirrhotic liver specimens with a resulting yield of 1.4 ± 0.5 × 106 cells per gram of the liver specimen and a viability rate of 52 ± 13%. It was found that the yield and viability of the liver cells were not correlated with the clinical and histological scores of the liver cirrhosis. A correlation was found between the hepatocyte yield obtained and the average number of hepatocytes counted in 10 microscopic fields of view. More viable cells were obtained from cirrhotic livers caused by chronic hepatitis B as compared to chronic hepatitis C in the same MELD score range. There was no correlation between the clinical and histological disease severity scores of liver cirrhosis and the outcome of hepatocytes isolation. It seems that the yield could depend on the type of hepatitis underlying the cirrhotic tissue. The study was registered at www.clinicaltrial.gov with the study identifier: NCT01335568.

Caring for civilians during peace keeping missions: priorities and decisions.

Humanitarian assistance is increasingly being offered by the military in operations other than war. Balancing issues of resources, priorities, and security is important but complicated. Sometimes errors are made that are costly, either in terms of public relations, morale, or lives. Unfortunately, not enough education of physicians and other medical personnel is done prior to the mission, as to how to weigh these aspects. No absolute guidelines can be recommended, as each situation is different, but some examples and guidelines are presented.

Military necessity versus the protection of the wounded and sick: a critical balance.

A realistic approach to humanitarian principles in the field of the Law of Armed Conflict should take into account "military necessity." Does military necessity also play a role in the medical field? The provisions regarding the treatment of the wounded and sick seem definite because they are at the core of International Humanitarian Law. The conduct of military medical personnel, the attention to be paid to the wounded and sick, as well as to medical equipment or facilities are provisions that derive from unyielding principles of care, respect, protection, and equality of treatment. To what extent may this analysis be considered as contrary to the common realism of LOAC? How far should medical personnel be requested to implement the Geneva standards in any circumstance? In fact, unless otherwise specified, military necessity can never lead to a reduction in these standards in the course of battle.

History of the International Committee of Military Medicine.

Founded in 1921, after World War I had revealed the importance of a closer cooperation among the Armed Forces Medical Services worldwide, the International Committee of Military Medicine (ICMM) is today an international intergovernmental organization including over 100 States and recognized by the World Health Organization as specialized in medico-military matters. Besides maintaining and strengthening the bonds among all medical services of member states, the ICMM promotes medico-military scientific activities, participates in the development of the medico-military setting of humanitarian operations in peace time, and organizes various training courses in International Humanitarian Law and Law on Armed Conflict. This article gives an overview of the historical milestones of the ICMM from 1921 until today.

Teaching the International Law of Armed Conflict to a wide military community.

The rules governing armed conflict are numerous and in many respects complex. In areas that are very complex, experts such as lawyers may be called in to assist, especially in the planning of military action. But the nature and tempo of warfare rarely allows a person in the field to enjoy such a luxury. Therefore, everyone involved in a military mission must have a basic working knowledge of their responsibilities according to the Law of Armed Conflict. The type and degree of knowledge will differ depending on the role and responsibility of the person. Accordingly, the knowledge base necessary for a foot soldier is often different from that which is required by a pilot. Even within a select group of combatants, the knowledge base required may differ from subgroup to subgroup. The knowledge required by a fighter pilot may be different, in some respects, from that of a pilot of an aircraft that provides transportation and logistical support. The fighter pilot must know what is an appropriate target; the transportation/logistical pilot may not need such knowledge.

Medical ethics in peace and in the armed conflict.

Global medical ethics on the basis of the General Declaration of Human Rights by the United Nations is a key subject for the 21st century. World Health Organization's new definition of health includes "spiritual health," a term that has to be defined in international consensus despite different anthropologies, cultures, and religions. Old issues in medical ethics such as assisted suicide are still waiting for global consensus among the "pro-life" and "pro-choice" parties. So far The Netherlands and Belgium are the only countries where euthanasia has been legalized, whereas the U.S. Supreme Court has denied a right of medically assisted suicide. The respect of nature is also the basis for guidelines in new issues in medical ethics such as gene therapy and human cloning, which are controversially discussed. Military medical ethics should provide regulations for morally correct decisions in armed conflicts including the war against international terrorism and in peacekeeping missions. Triage of the wounded, distribution of medical aid, and critical incident stress debriefing for soldiers and their relatives are key issues.

Experiences of the course. International Course on the Law of Armed Conflict.

This article reflects the experiences the commander and the chief medical officer of the course made. Creating an atmosphere of trust and mutual understanding helped to made participants at ease to discuss difficult issues openly. They learned that the most important problem for the participants was the issue of obeying orders, following medical ethical issues, and the simultaneous observance of Law of Armed Conflict. This gave rise to the greatest numbers of questions and concerns. Another hotly discussed issue was medical ethics in peace and war. Medical ethics is a very rapidly growing field of interest, which today is of concern to all of us, and this was reflected in the discussions of the participants. The last paragraph investigates what goals the course has achieved.

Aims of the 3rd international course on the Law of Armed Conflict of the International Committee for Military Medicine.

The International Committee for Military Medicine (ICMM) decided at the 32nd Congress in Vienna in 1998 to give the Surgeon General of the Swiss Armed Forces the mandate to organize its international courses on the Law of Armed Conflict (LOAC). The Swiss Federal Government fully honored and endorsed its obligation to organize these important international courses. It is in the continuing tradition of Switzerland, as a small neutral state, to support humanitarian help and all efforts to prevent war. As decided by the head of the government on April 3, 1998, the mandate of the LOAC Courses will be funded by the Swiss Confederation.

International humanitarian law: an introduction.

War is the ultimate form of human relations. From a Christian and Jewish point of view, it negates the most important of the Ten Commandments: "Thou shallt not kill." Is it pure illusion to believe that war may be subject to legal rules? Was Cicero possibly right when he wrote inter arma silent leges (in war, the law is silent)? The horrors of wars in the last decades have made it clear that Cicero's approach would lead us to the ultimate catastrophe, simply because the destructive potential of modern weaponry is so overwhelming that we need rules governing warfare. This article intends to provide the reader with a brief introduction to the Law of Armed Conflict, its genesis, and its basic rules and principles with particular emphasis on rules regulating medical issues. Finally, we would like to show ways to implement Law of Armed Conflict in peacetime and during armed conflict. Where appropriate, reference is also made to the complementary body of human rights law and to standards of medical ethics.