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.

Evaluation of 3D PLLA scaffolds coated with nano-thick collagen as carrier for hepatocytes.

Orthotopic liver transplantation is presently the most effectual method for the treatment of end-stage liver diseases. Though, one major issue is the restricted number of donor organs that are accessible. Hence, liver tissue engineering is under investigation with the goal of restoring liver functions. In this study, we investigated 3D porous scaffolds made of PLLA coated with a nano thick collagen layer (matrices). Primary rat dermal fibroblasts were used in a first study phase to check matrices' cytocompatibility. More than 70% of seeded cells could adhere and remain viable 24 and 48 hours after the seeding. To test the suitability of the matrices for human primary hepatocytes, HepaRG cells were seeded and analyzed for viability, adhesion rate, and functionality such as albumin secretion. About 80% of seeded HepaRG adhered to the scaffolds remaining viable up to 72 hours. Cells were homogeneously distributed in the entire scaffold with albumin secretion increasing with time. Our results indicate that PLLA collagen-coated matrices allow hepatocytes attachment and distribution throughout the 3D structure, as well as support cell functionality. Such matrices have been applied in our clinical phase II trial. Functional hepatocytes were successfully implanted in patients suffering from liver-cirrhosis with higher cell numbers and adhesions rate compared to our previous trial with the first matrix type and a general improvement in clinical condition.

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.

Formulation development of SYN-004 (ribaxamase) oral solid dosage form, a ß-lactamase to prevent intravenous antibiotic-associated dysbiosis of the colon.

SYN-004 (ribaxamase) delayed release drug product is a multi-particulate, hard capsule for oral delivery of a recombinant ß-lactamase enzyme designed to degrade ß-lactam antibiotics administered intravenously, and thus prevent colon dysbiosis. Here we describe the development of the SYN-004 enteric coated pellet formulation, which has been tested in multiple clinical trials. Since the SYN-004 drug substance is a buffered liquid, several binder excipients in different ratios were tested to facilitate binding of SYN-004 to sugar spheres. The binding systems were evaluated by droplet pre-evaluation and film casting tests. The most promising formulations were produced in small scale fluidized bed application runs and analyzed by dissolution tests and complementary analytical assays. Hydroxypropyl cellulose was selected as the preferred SYN-004 binding excipient. The formulation included a second, outer coat containing the enteric EUDRAGIT® L 30 D-55 polymer-based formulation to achieve gastric protection, and rapid SYN-004 release in the intestinal tract, when the pH rises above 5.5. Additional formulation improvements resulted in an increase in the SYN-004 load compared to a predecessor oral enzyme formulation (Ipsat P1A). Thus, a novel formulation and process for an orally administered enzyme was developed and used to manufacture drug product for clinical trials.

Allogeneic islet cells implant on poly-l-lactide matrix to reduce hyperglycaemia in streptozotocin-induced diabetic rat.

OBJECTIVE: To demonstrate the effects of allogeneic islet cell matrix implants for glycaemic control in rats with induced diabetes. METHOD: Sprague-Dawley rats were used as allogeneic donors of islet cells. Cells were seeded on three-dimensional proprietary poly-(l-lactide) matrices. Animals were rendered diabetic and a week later a matrix seeded with islet cells (IMI group) or a control matrix (placebo group) was implanted in the small bowel mesentery. Blood glucose levels were measured weekly for 12 weeks. After sacrifice, implant sections were Gomori stained for beta-cells and immuno-stained for insulin 3, 4, 5, and 6 months post implantation. RESULTS: 82% of seeded islet cells attached to the matrices. In the IMI group blood glucose levels were significantly reduced after implantation compared with before implantation across several time points. In the IMI group beta-cells and insulin-positive cells were identified at the implant site. CONCLUSION: The islet cell matrix implant reduced the blood glucose levels although complete normo-glycaemia was not established. The islet cell matrix implant may serve as an additional option for islet cell transplantation using 3D scaffold platforms for better survival and function of the islet cells.

A dialogue between naturopathy and critical medical anthropology: what constitutes holistic health?

Building on a dialogue between three trained naturopaths and a proponent of critical medical anthropology (CMA), this article highlights the relationship between health and society from the viewpoint of two fields that share this focal concern. Both naturopathy and CMA are committed to the notion of holistic health, although their approaches have historically been somewhat different. The responses of the three naturopaths to CMA exhibit both similarities and differences, particularly in terms of insights that CMA may make to naturopathy. This essay also articulates the CMA perspective of naturopathy and posits lessons that naturopathy can teach CMA.

The emergence of integrative medicine in Australia: the growing interest of biomedicine and nursing in complementary medicine in a southern developed society.

In this article, I examine the process by which some biomedical physicians and nurses in Australia have come to adopt various alternative therapies in their regimens of practice, largely in response to (1) the growing interest on the part of many Australians in what is generally called "complementary medicine", and (2) a recognition that biomedicine is not particularly effective in treating an array of chronic ailments. Some Australian biomedical physicians and nurses have come to embrace "integrative medicine," which purports to blend the best of biomedicine and complementary medicine, and have even created an Australasian Integrative Medical Association and established integrative medical training programs and centers. I argue that the adoption of alternative therapies and the development of integrative medicine on the part of Australian biomedical physicians and nurses constitute another national manifestation of the co-option of complementary and alternative medicine.

Toward a critical anthropology on the impact of global warming on health and human societies.

This op-ed essay urges medical anthropologists to join a growing number of public health scholars to examine the impact of global warming on health. Adopting a critical medical anthropology perspective, I argue that global warming is yet another manifestation of the contradictions of the capitalist world system. Ultimately, an serious effort to mitigate the impact of global warming not only on health but also settlement patterns and subsistence will require the creation of a new global political economy based upon social parity, democratic processes, and environmental sustainability.

Humiliation: the lasting effect of torture.

Although the physical effects of torture in surviving persons are well known, psychological wounds are lesser known and investigated. A new aspect of considerable impact is the notion of shame, self-humiliation, and the ensuing problems of degradation. Further research on the evolving concept of post-torture illness should be performed.

The changing face of the Course.

The commander of the International Course on Law of Armed Conflict, which is under the auspices of the International Committee of Military Medicine, summarizes his experiences and the changing subjects of interests during the course in Switzerland.

The drive for legitimation in Australian naturopathy: successes and dilemmas.

Whereas naturopathic physicians have either "licensure" or state-mandated "registration" in 13 US states and four Canadian provinces, naturopaths in Australia have thus far failed to obtain "statutory registration" in any political jurisdiction, despite the fact that chiropractors and osteopaths have done so in all Australian states and territories, and acupuncturists and Traditional Chinese Medicine practitioners have done so in the state of Victoria. Ironically, naturopathy and various other complementary medical systems are taught in many public tertiary institutions. This essay presents an overview of the development and the current socio-political status of naturopathy in Australia and its redefinition in some contexts as "natural therapies" and "natural medicine" or even as the major component of complementary medicine. It also examines reasons why the Australian state has come to express an interest in naturopathy along with other complementary medical systems.

The work of Andrew Weil and Deepak Chopra--two holistic health/New Age gurus: a critique of the holistic health/New Age movements.

Despite the popular roots of the holistic health/New Age movements, a growing number of biomedical physicians have become proponents of holistic health as well as New Age healing. Over the past two decades, Andrew Weil and Deepak Chopra, two biomedically trained physicians, have emerged as the visible and financially successful spokespersons of the movement. This article provides brief biographical sketches of Weil and Chopra and compares and contrasts their respective views on health, illness, healing, and health care. It also considers the response of various biomedical parties to these holistic health/New Age gurus who have attempted to integrate biomedicine and various alternative healing and metaphysical systems. Finally, this article argues that Weil and Chopra both epitomize the limitations of the holistic health/New Age movements, albeit in different ways.

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.