Background: The success of a cochlear implant (CI), which is the standard therapy for patients suffering from severe to profound sensorineural hearing loss, depends on the number and excitability of spiral ganglion neurons (SGNs). Brain-derived neurotrophic factor (BDNF) has a protective effect on SGNs but should be applied chronically to guarantee their lifelong survival. Long-term administration of BDNF could be achieved using genetically modified mesenchymal stem cells (MSCs), but these cells should be protected – by ultra-high viscous (UHV-) alginate (‘alginate-MSCs’) – from the recipient immune system and from uncontrolled migration. Methods: Brain-derived neurotrophic factor-producing MSCs were encapsulated in UHV-alginate. Four experimental groups were investigated using guinea pigs as an animal model. Three of them were systemically deafened and (unilaterally) received one of the following: (I) a CI; (II) an alginate-MSC-coated CI; (III) an injection of alginate-embedded MSCs into the scala tympani followed by CI insertion and alginate polymerization. Group IV was normal hearing, with CI insertion in both ears and a unilateral injection of alginate-MSCs. Using acoustically evoked auditory brainstem response measurements, hearing thresholds were determined before implantation and before sacrificing the animals. Electrode impedance was measured weekly. Four weeks after implantation, the animals were sacrificed and the SGN density and degree of fibrosis were evaluated. Results: The MSCs survived being implanted for 4 weeks in vivo . Neither the alginate-MSC injection nor the coating affected electrode impedance or fibrosis. CI insertion with and without previous alginate injection in normal-hearing animals resulted in increased hearing thresholds within the high-frequency range. Low-frequency hearing loss was additionally observed in the alginate-injected and implanted cochleae, but not in those treated only with a CI. In deafened animals, the alginate-MSC coating of the CI significantly prevented SGN from degeneration, but the injection of alginate-MSCs did not. Conclusion: Brain-derived neurotrophic factor-producing MSCs encapsulated in UHV-alginate prevent SGNs from degeneration in the form of coating on the CI surface, but not in the form of an injection. No increase in fibrosis or impedance was detected. Further research and development aimed at verifying long-term mechanical and biological properties of coated electrodes in vitro and in vivo , in combination with chronic electrical stimulation, is needed before the current concept can be tested in clinical trials.

An easy and efficient route to synthesize gel materials based on polymeric ionic liquids (PILs) is presented. The radical polymerization of imidazolium (Im)‐based ionic liquids (ILs) bearing a vinyl group ([VEIm][Br], [VEIm][Ac], [VBIm][Br], [VBIm][Cl]) with crosslinker (CL) N,N′‐methylenebisacrylamide (Bis) in water results in polyionic liquid hydrogels. Thermal and mechanical properties (tensile and compression tests) are investigated and compared with two different types of hydrogels. One is a polyacrylamide (PAAm) hydrogel having covalent‐type crosslinking. The other is an alginate‐based hydrogel having ionic‐type crosslinking. Prepared IL‐hydrogel materials provide favorable flexibility, adjustable by varying the CL ratio and water content. The higher the CL ratio is, the higher the fragility of the gel matrix. The gelation time of the hydrogels depends on the alkyl chain length, as well as the size of the anion.

The surface charge of a biomaterial represents a promising tool to direct cellular behavior, which is crucial for therapeutic approaches in regenerative medicine. To expand the understanding of how the material surface charge affects protein adsorption and mesenchymal stem cell behavior, differently charged surfaces with zeta potentials spanning from −25 mV to +15 mV were fabricated by the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that the increase of the biomaterials surface charge resulted in enhanced quantities of biologically available, surface-attached proteins. Since different surface charges were equalized after protein adsorption, mesenchymal stem cells interacted rather with diverse protein compositions instead of different surface features. Besides an enhanced cell attachment to increasingly positively charged surfaces, the cell spreading area and the expression of adhesion-related genes integrin α5 and tensin 1 were found to be increased after adhesion. Moreover, first results indicate a potential impact of the surface charge on mesenchymal stem cell differentiation towards bone and fat cells. The improved understanding of surface charge-related cell behavior has significant impact on the design of biomedical devices and artificial organs.

Summary:The aim of this study was to reduce the rate of graft failure after HLA non-identical stem cell transplantation by using G-CSF mobilized CD34 ؉ peripheral blood progenitor cells (PBPC), either in combination with bone marrow or as single grafts. To prevent GVHD, PBPC were highly purified, resulting in a 5 to 6 log T cell depletion. In additon to T cell depletion no further GVHD prophylaxis was used. We transplanted 23 pediatric patients with life-threatening malignant or non-malignant hematological disorders, who had no available matched donor. Engraftment was obtained in 18 of 21 evaluable patients. Five patients developed acute GVHD of grade II and III, which became chronic in four cases and was fatal in four. The use of highly purified PBPC allowed the exact quantification of residual T cells in the grafts and a strict correlation between the residual T cell load and the development of GVHD was observed: patients with GVHD had received numbers of T cells between 8 and 20 ؋ 10 4 /kg, whereas patients without GVHD were grafted with T cell numbers ranging from 0.7 to 6.0 ؋ 10 4 /kg. We therefore clearly demonstrate that a residual T cell content of Ͻ5 ؋ 10 4 /kg is safe for prevention of GVHD after HLA non-identical PBPC transplantation in children. Keywords: HLA non-identical transplantation; peripheral blood progenitor cells; grafted T cell number; GVHD HLA haplo-identical BMT with T cell depletion (TCD) has been used successfully to treat children with primary immunodeficiency disorders. [1][2][3] In patients with other diseases, this transplant approach has frequently failed because of graft rejection. [4][5][6] Graft failure may result from the profound T cell depletion required to prevent GVHD, with the ensuing loss of the graft-enhancing effect mediated by T cells. 7,8 More intensive immunosuppressive conditioning to counterbalance this disadvantage has usually had limited success because of significant complications from toxicity. Less vigorously T cell-depleted grafts carry the risk of severe GVHD. From animal models it is clear that engraftment may also be improved by increasing the number of grafted cells, either using unmanipulated bone marrow, taking advantage of the effect of alloreactive T cells or, as shown in recent studies, by using high numbers of highly purified T cell-depleted stem cells. 9 The latter approach was used by Aversa et al to transplant patients with leukemia from HLA non-identical family donors using either a combination of purified peripheral blood progenitor cells (PBPC) and T cell-depleted marrow or, in more recent patients, PBPC alone. 10-12 A remarkably high engraftment rate of more than 90% was observed.Here we report results of a pilot study in pediatric patients, where we explored a comparable transplant approach. Like the findings of Aversa et al, we observed a high engraftment rate of 86%. In contrast, GVHD developed in the initial patients, but was completely preventable in patients receiving grafts containing fewer T cells than 5 ϫ 10 4 /kg. Patients and meth...