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Given their native-like biological properties, high growth factor retention capacity and porous nature, sulfated-polysaccharide-based scaffolds hold great promise for a number of tissue engineering applications. Specifically, as they mimic important properties of tissues such as bone and cartilage they are ideal for orthopaedic tissue engineering. Their biomimicry properties encompass important cell-binding motifs, native-like mechanical properties, designated sites for bone mineralisation and strong growth factor binding and signaling capacity. Even so, scientists in the field have just recently begun to utilise them as building blocks for tissue engineering scaffolds. Most of these efforts have so far been directed towards in vitro studies, and for these reasons the clinical gap is still substantial. With this review paper, we have tried to highlight some of the important chemical, physical and biological features of sulfated-polysaccharides in relation to their chondrogenic and osteogenic inducing capacity. Additionally, their usage in various in vivo model systems is discussed. The clinical studies reviewed herein paint a promising picture heralding a brave new world for orthopaedic tissue engineering., (Copyright © 2019. Published by Elsevier Ltd.)

The immobilization of cells within alginate-poly-l-lysine-alginate (APA) microcapsules has been demonstrated to be an effective technology design for long term delivery of therapeutic products. Despite promising advances, biosafety aspects still remain to be improved. Here, we describe a complete characterization of the strategy based on TGL triple-fusion reporter gene--which codifies for Herpes Simplex virus type 1 thymidine-kinase (HSV1-TK), green fluorescent protein (GFP) and Firefly Luciferase--(SFG(NES)TGL) to inactivate encapsulated cells and their therapeutic effects. Myoblasts genetically engineered to secrete erythropoietin (EPO) were retroviraly transduced with the SFG(NES)TGL plasmid to further characterize their ganciclovir (GCV)-mediated inactivation process. GCV sensitivity of encapsulated cells was 100-fold lower when compared to cells plated onto 2D surfaces. However, the number of cells per capsule and EPO secretion decayed to less than 15% at the same time that proliferation was arrested after 14 days of GCV treatment in vitro. In vivo, ten days of GCV treatment was enough to restore the increased hematocrit levels of mice implanted with encapsulated TGL-expressing and EPO-secreting cells. Altogether, these results show that TGL triple-fusion reporter gene may be a good starting point in the search of a suitable biosafety strategy to inactivate encapsulated cells and control their therapeutic effects., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF), an angiogenic protein with important neurotrophic and neuroprotective actions, is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders. The aim of this study was to generate encapsulated VEGF-secreting cells and implant them in a transgenic mouse model of AD, the double mutant amyloid precursor protein/presenilin 1 (APP/Ps1) mice, which shows a disturbed vessel homeostasis. We report that, after implantation of VEGF microcapsules, brain Abeta burden, hyperphosphorylated-tau and cognitive impairment attenuated in APP/Ps1 mice. Based on the neurovascular hypothesis, our findings suggest a new potential therapeutic approach that could be developed for AD, to enhance Abeta clearance and neurovascular repair, and to protect the cognitive behavior. Stereologically-implanted encapsulated VEGF-secreting cells could offer an alternative strategy in the treatment of AD., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

One important challenge in biomedicine is the ability to cryogenically preserve not only cells, but also tissue-engineered constructs. In the present paper, alginate-poly-l-lysine-alginate (APA) microcapsules containing erythropoietin (Epo)-secreting C(2)C(12) myoblasts were elaborated, characterized and tested both in vitro and in vivo. Dimethylsulfoxide (DMSO) was selected as cryoprotectant to evaluate the maintenance of physiological activity of cryopreserved microencapsulated myoblasts employing procedures based on freezing protocols up to a 45-day cryopreservation period. High chemical resistance of the cryopreserved microcapsules was observed using 10% DMSO as cryoprotectant following a standard slow-cooling procedure. Although a 42% reduction in Epo release from the microencapsulated cells was observed in comparison with the non-cryopreserved group, the in vivo biocompatibility and functionality of the encapsulated cells subcutaneously implanted in Balb/c mice was corroborated by high and sustained hematocrit levels over 194 days and lacking immunosuppressive protocols. No major host reaction was observed. Based on the results obtained in our study, a slow-cooling protocol using 10% DMSO as cryoprotectant (confirmed for cryopreservation periods up to 45 days) might be considered a suitable therapeutic strategy if the long-term storage of microencapsulated cells, such as C(2)C(12) myoblasts is pretended.

Bioencapsulation involves the envelopment of tissues or biological active substances in semipermeable membranes. Bioencapsulation has been shown to be efficacious in mimicking the cell's natural environment and thereby improves the efficiency of production of different metabolites and therapeutic agents. The field of application is broad. It is being applied in bioindustry and biomedicine. It is clinically applied for the treatment of a wide variety of endocrine diseases. During the past decades many procedures to fabricate capsules have been described. Unfortunately, most of these procedures lack an adequate documentation of the characterization of the biocapsules. As a result many procedures show an extreme lab-to-lab variation and many results cannot be adequately reproduced. The characterization of capsules can no longer be neglected, especially since new clinical trials with bioencapsulated therapeutic cells have been initiated and the industrial application of bioencapsulation is growing. In the present review we discuss novel Approached to produce and characterize biocapsules in view of clinical and industrial application. A dominant factor in bioencapsulation is selection and characterization of suitable polymers. We present the adequacy of using high-resolution NMR for characterizing polymers. These polymers are applied for producing semipermeable membranes. We present the pitfalls of the currently applied methods and provide recommendations for standardization to avoid lab-to-lab variations. Also, we compare and present methodologies to produce biocompatible biocapsules for specific fields of applications and we demonstrate how physico-chemical technologies such as FT-IR, XPS, and TOF-SIMS contribute to reproducibility and standardization of the bioencapsulation process. During recent years it has become more and more clear that bioencapsulation requires a multidisciplinary approach in which biomedical, physical, and chemical technologies are combined. For adequate reproducibility and for understanding variations in outcome of biocapsules it is advisable if not mandatory to include the characterization processes presented in this review in future studies.

Platelet-rich preparations constitute a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of this approach has stimulated its therapeutic use in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, tissue engineering among others. Here we discuss the important progress that has been accomplished in the field of platelet-rich preparations in the last few years. Some of the most interesting therapeutic applications of this technology are discussed as are some of the limitations, future challenges and directions in the field.

Implantation of microencapsulated cells has been proposed as a therapy for a wide variety of diseases. An absolute requirement is that the applied microcapsules have an optimal biocompatibility. The alginate-poly-L-lysine system is the most commonly applied system but is still suffering from tissue responses provoked by the capsule materials. In the present study, we investigate the biocompatibility of microcapsules elaborated with two commonly applied alginates, i.e. an intermediate-G alginate and a high-G alginate. These alginates were coated with poly-L-lysine (PLL), poly-D-lysine (PDL) and poly-L-ornithine (PLO). The main objective of this study is to determine the interaction of each alginate matrix with the different polycations and the potential impact of these interactions in the modulation of the host's immune response. To address these issues the different types of microcapsules were implanted into the peritoneal cavity of rats for I month. After this period the microcapsules were recovered and they were evaluated by different techniques. Monochromatised X-ray photoelectron spectroscopy (XPS) was performance and the degree of capsular recovery, overgrowth on each capsule, and the cellular composition of the overgrowth were evaluated by histology. Our results illustrate that the different observed immune responses are the consequence of the variations in the interactions between the polycations and alginates rather than to the alginates themselves. Our results suggest that PLL is the best option available and that we should avoid using PLO and PDL in its present form since it is our goals to produce capsules that lack overgrowth and do not induce an immunological response as such.

Cell microencapsulation holds promise for the treatment of many diseases by the continuous delivery of therapeutic products. The biocompatibility of the microcapsules and their biomaterials components is a critical issue for the long-term efficacy of this technology. The objective of this paper is to provide detailed information about the principal factors affecting the biocompatibility of alginates and alginate-poly-l-lysine microcapsules, which are the most frequently employed biomaterials and encapsulation devices for cell immobilization, respectively. Some of these factors include the alginate composition and purification, the selection of the polycation, the interactions between the alginates and the polycation, the microcapsule fabrication process, the uniformity of the devices and the implantation procedure. Improved knowledge will lead to the production of standardized transplantation-grade biomaterials and biocompatible microcapsules.