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In recent years, interest in tissue engineering and its solutions has increased considerably. In particular, scaffolds have become fundamental tools in bone graft substitution and are used in combination with a variety of bio-agents. However, a long-standing problem in the use of these conventional scaffolds lies in the impossibility of re-loading the scaffold with the bio-agents after implantation. This work introduces the magnetic scaffold as a conceptually new solution. The magnetic scaffold is able, via magnetic driving, to attract and take up in vivo growth factors, stem cells or other bio-agents bound to magnetic particles. The authors succeeded in developing a simple and inexpensive technique able to transform standard commercial scaffolds made of hydroxyapatite and collagen in magnetic scaffolds. This innovative process involves dip-coating of the scaffolds in aqueous ferrofluids containing iron oxide nanoparticles coated with various biopolymers. After dip-coating, the nanoparticles are integrated into the structure of the scaffolds, providing the latter with magnetization values as high as 15 emu g(-)(1) at 10 kOe. These values are suitable for generating magnetic gradients, enabling magnetic guiding in the vicinity and inside the scaffold. The magnetic scaffolds do not suffer from any structural damage during the process, maintaining their specific porosity and shape. Moreover, they do not release magnetic particles under a constant flow of simulated body fluids over a period of 8 days. Finally, preliminary studies indicate the ability of the magnetic scaffolds to support adhesion and proliferation of human bone marrow stem cells in vitro. Hence, this new type of scaffold is a valuable candidate for tissue engineering applications, featuring a novel magnetic guiding option., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate intravascular xenotransplantation of macroencapsulated pancreatic islet cells in the process of the treatment of diabetes mellitus type 1 without immunosuppressive therapy., Material and Methods: Xenogenic intravascular transplantation was performed in 19 patients with diabetes mellitus (type 1) having high insulin demand and frequent hypo- and hyperglycemic comas without immunosuppressive therapy. The culture was obtained from 3rd trimester rabbit fetuses. Cell culture suspension was encapsulated into microporous macrocapsule made of nylon and grafted into the deep femoral artery or the forearm cubital vein after performing arteriovenous anastomosis., Results: For 2 years after transplantation, positive results were observed in 14 recipients (73.7%). The total decrease of insulin demand was 60-65%, and hypo- and hyperglycemic comas disappeared completely, while C-peptide and immunoreactive insulin levels significantly increased, reversely correlating with the fructosamin level, as a protein glycation marker., Conclusions: Xenotransplantation of pancreatic islet cells with their subsequent grafting into the vascular lumen creates double immune isolation and allows overcoming acute and chronic graft rejection without immuno-suppressive therapy. It considerably decreases insulin demand, compensates hypo- and hyperglycemic conditions, makes the course of diabetes stable, and improves the quality of the patients' life.

Experimental dogs with alloxan-induced diabetes mellitus (n = 22) were transplanted into the abdominal aorta lumen with macroencapsulated xenogenic rabbit islet cells without immunosuppressive therapy. The investigation showed normalization of the blood glucose level and disappearance of diabetes mellitus symptoms. Morphological and immunohistochemical investigations 13 months later demonstrated preservation and functional activity of up to 60% of the transplanted islet cells. Meanwhile by month 6 a structure similar to the Islet of Langerhans had formed in the capsule. The majority of the mass of cells was insulin-positive by immunohistochemical investigation. The bloodstream appears to be an immune-privileged zone, where no graft rejection develops and long-term preservation-function of xenogenic islet cells may be possible. Macroencapsulated islets transplanted into the vascular lumen may form an endocrine apparatus of a bioartificial pancreas.

The article presents a new method of surgical treatment of experimental diabetes mellitus in a rabbit to dog model. Rabbit islet cells, which had been macroencapsulated into a microporous polyamide, were implanted into the dog aorta without immunosuppressive therapy. Euglycemia was reached at 4 to 5 days and persisted for 12 months. Morphological and immunohistochemical investigations showed long-term preservation of islet cell viability, absence of graft rejection, and formation of a biological artificial pancreas in the capsule at 6 months after transplantation. Up to 60% of transplanted cells were still viable 12 months later. The major factor contributing to preservation of islet cells is neo-angiogenesis, which develops during the first weeks after transplantation. Double immune isolation of islet cells by macroencapsulation with implantation into the blood stream allows the use of either xenotransplantation or allotransplantation.

It is suggested that the development of insulin-dependent diabetes mellitus (IDDM) is due to insufficiency of local immunoneuroendocrine system (LINES), which prevents development of the pathological process in the insular tissue at the very early stages. The further disbalance between LINES and CNS and development of pathology occurs with a very active involvement of immunocompetent cells and their effector molecules (autoantibodies, cytokines). We believe that finding of mechanisms of cell interactions inside LINES (beta-cells, neurons, lymphocytes and macrophages) at the early stages will serve a basis for IDDM prevention.