Biomatter最新文献

Therapeutic monoclonal antibodies have revolutionized the treatment of cancer and other diseases. However, several limitations of antibody-based treatments, such as the cost of therapy and the achievement of sustained plasma levels, should be still addressed for their widespread use as therapeutics. The use of cell and gene transfer methods offers additional benefits by producing a continuous release of the antibody with syngenic glycosylation patterns, which makes the antibody potentially less immunogenic. In vivo secretion of therapeutic antibodies by viral vector delivery or ex vivo gene modified long-lived autologous or allogeneic human mesenchymal stem cells may advantageously replace repeated injection of clinical-grade antibodies. Gene-modified autologous mesenchymal stem cells can be delivered subcutaneously embedded in a non-immunogenic synthetic extracellular matrix-based scaffold that guarantees the survival of the cell inoculum. The scaffold would keep cells at the implantation site, with the therapeutic protein acting at distance (immunotherapeutic organoid), and could be retrieved once the therapeutic effect is fulfilled. In the present review we highlight the practical importance of living cell factories for in vivo secretion of recombinant antibodies.

Focal stroke is a disabling disease with lifelong sensory, motor and cognitive impairments. Given the paucity of effective clinical treatments, basic scientists are developing novel options for protection of the affected brain and regeneration of lost tissue. Tissue bioengineering and stem/progenitor cell treatments have both been individually pursued for stroke neural repair therapies, with some benefit in tissue recovery. Emerging directions in stroke neural repair approaches combine these two therapies to use biopolymers with stem/progenitor transplants to promote greater cell survival in the transplant and directed delivery of bioactive molecules to the transplanted cells and the adjacent injured tissue. In this review the background literature on a combined use of neural stem/progenitor cells encapsulated in hyaluronan gels is discussed and the way this therapeutic approach can affect the important processes involved in brain tissue reconstruction, such as angiogenesis, axon regeneration, neural differentiation and inflammation is clarified. The glycosaminoglycan hyaluronan can optimize those processes and be employed in a successful neural tissue engineering approach.

Adoptive transfer of stem cells has shown potential as an effective treatment for acute kidney injury (AKI). The current strategy for adoptive transfer of stem cells is by intravenous injection. However, this conventional method of stem cell delivery is riddled with problems causing reduced efficacy of the therapeutic potential of delivered stem cells. This review summarizes the recent advancements in an alternative method of stem cell delivery for treatment of AKI, embedding stem cells in hyaluronic acid (HA-) based hydrogels followed by their implantation. Furthermore, one stem cell type in particular, endothelial progenitor cells (EPC), have shown remarkable therapeutic benefits for treatment of AKI when delivered by HA-hydrogels. The review also summarizes the delivery of EPC by HA-hydrogels in the setting of AKI.

The unique vibrational properties inherent to the human vocal fold have a significant detrimental impact on wound healing and scar formation. Hydrogels have taken prominence as a tissue engineered strategy to restore normal vocal structure and function as cellularity is low. The frequent vibrational and shear forces applied to, and present in this connective tissue make mechanical properties of such hydrogels a priority in this active area of research. Hyaluronic acid has been chemically modified in a variety of ways to address cell function while maintaining desirable tissue mechanical properties. These various modifications have had mixed results when injected in vivo typically resulting in better biomechanical function but not necessarily with a concomitant decrease in tissue fibrosis. Recent work has focused on seeding mesenchymal progenitor cells within 3D architecture of crosslinked hydrogels. The data from these studies demonstrate that this approach has a positive effect on cells in both early and late wound healing, but little work has been done regarding the biomechanical effects of these treatments. This paper provides an overview of the various hyaluronic acid derivatives, their crosslinking agents, and their effect when implanted into the vocal folds of various animal models.

The objective in this study was to develop an osteoconductive, biodegradable and rifampicin releasing bone filling composite material for the treatment of osteomyelitis, a bacterial infection of bone that is very difficult and expensive to treat. The composite material will be used together with a ciprofloxacin releasing composite, because of the rapid development of resistant bacteria when rifampicin is used alone. Three composites were manufactured by twin-screw extrusion. The polymer matrix for the composites was poly(L-lactide-co-ε-caprolactone) 70/30 and all the composites contained 8 wt% (weight percent) of rifampicin antibiotic. The β-TCP contents of the composites were 0 wt%, 50 wt% and 60 wt%. The composites were sterilized by gamma irradiation before in vitro degradation and drug release tests. The hydrolytical degradation of the studied composites proceeded quickly and the molecular weight of the polymer component of the composites decreased rapidly. Rifampicin release occurred in four phases in which the high β-TCP content of the samples, polymer degradation and mass loss all played a role in determining the phases. The ceramic component was seen to have a positive effect on the drug release. The composite with 50 wt% of β-TCP showed the most promising rifampicin release profile and it also showed activity against a common osteomyelitis causing bacteria Pseudomonas aeruginosa. A clear inhibition zone was formed in 16 h incubation. Overall, the tested materials showed great potential to be developed into a bone filler material for the treatment of osteomyelitis or other bone related infections in combination with the ciprofloxacin releasing materials.

To meet the increasing demand for liver tissue engineering, various three-dimensional (3D) liver cell culture techniques have been developed. Nevertheless, conventional liver cell culture techniques involving the suspending cells in extracellular matrix (ECM) components and the seeding of cells into 3D biodegradable scaffolds have an intrinsic shortcoming, low cell-scaffold ratios. We have developed a microporous membrane-based liver cell culture technique. Cell behaviors and tissue organization can be controlled by membrane geometry, and cell-dense thick tissues can be reconstructed by layering cells cultured on biodegradable microporous membranes. Applications extend from liver parenchymal cell monoculture to multi-cell type cultures for the reconstruction of 3D functional liver tissue. This review focuses on the expanding role for microporous membranes in liver tissue engineering, primarily from our research.

One of the backbones in nanomedicine is to deliver drugs specifically to unhealthy cells. Drug nanocarriers can cross physiological barriers and access different tissues, which after proper surface biofunctionalization can enhance cell specificity for cancer therapy. Recent developments have highlighted the potential of mesoporous silica (PSiO(2)) and silicon (PSi) nanoparticles for targeted drug delivery. In this review, we outline and discuss the most recent advances on the applications and developments of cancer therapies by means of PSiO(2) and PSi nanomaterials. Bio-engineering and fine tuning of anti-cancer drug vehicles, high flexibility and potential for sophisticated release mechanisms make these nanostructures promising candidates for "smart" cancer therapies. As a result of their physicochemical properties they can be controllably loaded with large amounts of drugs and coupled to homing molecules to facilitate active targeting. The main emphasis of this review will be on the in vitro and in vivo studies.

Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect.

Electrospun fibers based on aliphatic polyesters, such as poly(ε-caprolactone) (PCL), have been widely used in regenerative medicine and drug delivery applications due to their biocompatibility, low cost and ease of fabrication. However, these aliphatic polyester fibers are hydrophobic in nature, resulting in poor wettability, and they lack functional groups for decorating the scaffold with chemical and biological cues. Current strategies employed to overcome these challenges include coating and blending the fibers with bioactive components or chemically modifying the fibers with plasma treatment and reactants. In the present study, we report on designing multifunctional electrospun nanofibers based on the inclusion complex of PCL-α-cyclodextrin (PCL-α-CD), which provides both structural support and multiple functionalities for further conjugation of bioactive components. This strategy is independent of any chemical modification of the PCL main chain, and electrospinning of PCL-α-CD is as easy as electrospinning PCL. Here, we describe synthesis of the PCL-α-CD electrospun nanofibers, elucidate composition and structure, and demonstrate the utility of functional groups on the fibers by conjugating a fluorescent small molecule and a polymeric-nanobead to the nanofibers. Furthermore, we demonstrate the application of PCL-α-CD nanofibers for promoting osteogenic differentiation of human adipose-derived stem cells (hADSCs), which induced a higher level of expression of osteogenic markers and enhanced production of extracellular matrix (ECM) proteins or molecules compared with control PCL fibers.