Development of functionalized alginate-based hydrogels to reduce fibrosis in the transplantation of microencapsulated cells

Nowadays, the development of cell therapy relies mainly on the advances made toward cell microencapsulation which allows to evade the need for immunosuppression during cell transplantation. Among the materials considered for cell encapsulation, hydrogels distinguish themselves by their exceptional properties. Due to its gelling properties in contact with divalent cations, the biopolymer sodium alginate (Na-alg), has been widely studied for the microencapsulation and transplantation of cells. However, several defects notably in permselectivity and durability in vivo is limiting the translation of alginate-based hydrogels in clinical applications. In addition, the transplantation of cells without immunosuppressive treatment have to face adverse host responses such as inflammation and fibrosis. At the moment, several approaches have been considered for the development of an ideal material for cell encapsulation; however many challenges still remain in this domain. Hence, this research project focused on the development of hydrogels in order to improve their properties toward cell encapsulation. The first part of this research focused on the development of new types of one-component hybrid alginate-based hydrogels. These hydrogels combine the gelling properties of Na-alg with covalent crosslinking within the same polymeric structure. In order to do so, a new synthetic approach was developed allowing the functionalization on the hydroxyl position of alginate with heterobifunctional poly(ethylene glycol) (PEG) linkers through carbamate bond. This allowed to maintain the carboxyl moieties available for the formation of electrostatic interactions. Two types of one-component hybrid hydrogel were developed with this method adding either thiols or lipoyl moieties on alginate leading to an improvement of mechanical properties while preserving a good biocompatibility. Yet, transplantation of encapsulated cells in a foreign host body have to face immune response, in particular inflammation and pericapsular fibrosis overgrowth (PFO) which ultimately leads to necrosis of the encapsulated cells and loss of graft functionality. Therefore, the second part of this research project focused on tuning the composition of the polymeric components of the hydrogels with anti-inflammatory agents which would reduce PFO in vivo. Different anti-inflammatory agents were considered for this purpose. The best candidate (ketoprofen) was then PEGylated via either ester or amide bond and grafted on the backbone of alginate to ensure a controlled release at the site of transplantation. By analyzing the fibrotic tissue around the microspheres, it was observed that the incorporation of ketopreofen on the structure of the hydrogel significantly reduced PFO 30 days after transplantation. In summary, Na-alg was functionalized with a new synthetic methodology allowing the incorporation of either functionalities reinforcing the mechanical resistance of the hydrogel or anti-inflammatory compounds improving the biocompatibility of the graft

Erratum to: Transverse dental arch relationship at 9 and 12 years in children with unilateral cleft lip and palate treated with infant orthopedics: a randomized clinical trial (DUTCHCLEFT)

The original version of the above article contained a mistakedue to incorrect alignment of entries in Tables 11 and 14during production. The entries are presented correctly below

Magic wand and the Enigma of the Sphinx

This paper presents an evaluation of the benefits and user acceptance of a multimodal interface in which the user interacts with a game-like interactive virtual reality application "The Enigma of the Sphinx". The interface consists of a large projection screen as the main display, a "magic wand", a stereo sound system and the user's voice for "casting spells". We present our conclusions concerning "friendliness" and sense of presence, based on observations of more than 150 users in a public even

Synthesis strategies to extend the variety of alginate-based hybrid hydrogels for cell microencapsulation

The production of hydrogel microspheres (MS) for cell immobilization, maintaining the favorable properties of alginate gels but presenting enhanced performance in terms of in vivo durability and physical properties, is desirable to extend the therapeutic potential of cell transplantation. A novel type of hydrogel MS was produced by straightforward functionalization of sodium alginate (Na-alg) with heterotelechelic poly(ethylene glycol) (PEG) derivatives equipped with either end thiol or 1,2-dithiolane moieties. Activation of the hydroxyl moieties of the alginate backbone in the form of imidazolide intermediate allowed for fast conjugation to PEG oligomers through a covalent carbamate linkage. Evaluation of the modified alginates for the preparation of MS combining fast ionic gelation ability of the alginate carboxylate groups and slow covalentcross-linking provided by the PEG-end functionalities highlighted the influence of the chemical composition of the PEG-grafting units on the physical characteristics of the MS. The mechanical properties of the MS (resistance and shape recovery) and durability of PEG-grafted alginates in physiological environment can be adjusted by varying the nature of the end functionalities and the length of the PEG chains. In vitro cell microencapsulation studies and preliminary in vivo assessment suggested the potential of these hydrogels for cell transplantation applications

[Clinical results of bone anchors for orthodontic anchorage; the indications and surgical complications],[Clinical results of bone anchors for orthodontic anchorage; the indications and surgical complications]

Contains fulltext : 79819.pdf (publisher's version ) (Open Access)In order to make teeth-movement possible, orthodontic anchorage is necessary. Neighbouring teeth, a headgear, dental implants and bone anchors can be used. During the period 2002-2007 158 bone anchors have been placed in 84 patients by an oral surgeon after referral by an orthodontist in order to achieve anchorage for orthodontic treatment. The bone anchor consists of a titanium osteosynthesis-plate ending in a round neck perforating the soft tissue and a cylinder attached to it. The indications for placement, results and complications were registered. 15 anchors (9,5%) were lost prematurely and in 13 cases (8,2%) complications needing surgical intervention were reported. It is concluded that zygoma-bone anchor is a good alternative for orthodontic anchorage and the number of complications is acceptable, though there is room for improvement