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"Tissue Scaffolds."
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Electrospun Fibrous Scaffolds for Tissue Engineering: Viewpoints on Architecture and Fabrication
Electrospinning has been used for the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several decades. Electrospun fibrous scaffolds provide nanoscale/microscale fibrous structures with interconnecting pores, resembling natural ECM in tissues, and showing a high potential to facilitate the formation of artificial functional tissues. In this review, we summarize the fundamental principles of electrospinning processes for generating complex fibrous scaffold geometries that are similar in structural complexity to the ECM of living tissues. Moreover, several approaches for the formation of three-dimensional fibrous scaffolds arranged in hierarchical structures for tissue engineering are also presented.
Journal Article
Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution
Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.
Journal Article
Designing Smart Biomaterials for Tissue Engineering
The engineering of human tissues to cure diseases is an interdisciplinary and a very attractive field of research both in academia and the biotechnology industrial sector. Three-dimensional (3D) biomaterial scaffolds can play a critical role in the development of new tissue morphogenesis via interacting with human cells. Although simple polymeric biomaterials can provide mechanical and physical properties required for tissue development, insufficient biomimetic property and lack of interactions with human progenitor cells remain problematic for the promotion of functional tissue formation. Therefore, the developments of advanced functional biomaterials that respond to stimulus could be the next choice to generate smart 3D biomimetic scaffolds, actively interacting with human stem cells and progenitors along with structural integrity to form functional tissue within a short period. To date, smart biomaterials are designed to interact with biological systems for a wide range of biomedical applications, from the delivery of bioactive molecules and cell adhesion mediators to cellular functioning for the engineering of functional tissues to treat diseases.
Journal Article
Novel Collagen/Gelatin Scaffold with Sustained Release of Basic Fibroblast Growth Factor: Clinical Trial for Chronic Skin Ulcers
Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), which is capable of sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers that had not healed in at least 4 weeks were treated with CGS impregnated with bFGF at 7 or 14 μg/cm
2
after debridement, and the wound bed improvement was assessed 14 days after application. Wound bed improvement was defined as a granulated and epithelialized area on day 14 with a proportion to the baseline wound area after debridement of 50% or higher. The wound area, the wound area on day 14, and the granulation area on day 14 were independently measured by blinded reviewers in a central review using digital images of wounds taken with a calibrator. Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS. From May 2010 to June 2011, 17 patients were enrolled and, in 16 patients, the wound bed improved. Among the randomized patients in step 2, no significant difference was seen between the low-dose group and the high-dose group. No serious adverse reactions were observed. Adverse reactions with a clear causal relationship to the study treatment were mild and patients quickly recovered from them. This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. This combination therapy could be a promising therapy for chronic skin ulcers.
Journal Article
High-strength silk protein scaffolds for bone repair
Biomaterials for bone tissue regeneration represent a major focus of orthopedic research. However, only a handful of polymeric biomaterials are utilized today because of their failure to address critical issues like compressive strength for load-bearing bone grafts. In this study development of a high compressive strength (approximately 13 MPa hydrated state) polymeric bone composite materials is reported, based on silk protein-protein interfacial bonding. Micron-sized silk fibers (10–600 µm) obtained utilizing alkali hydrolysis were used as reinforcement in a compact fiber composite with tunable compressive strength, surface roughness, and porosity based on the fiber length included. A combination of surface roughness, porosity, and scaffold stiffness favored human bone marrow-derived mesenchymal stem cell differentiation toward bone-like tissue in vitro based on biochemical and gene expression for bone markers. Further, minimal in vivo immunomodulatory responses suggested compatibility of the fabricated silk-fiber-reinforced composite matrices for bone engineering applications.
Journal Article
3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration
Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.
Journal Article
Silver nanoparticle loaded collagen/chitosan scaffolds promote wound healing via regulating fibroblast migration and macrophage activation
Treatment of full-thickness skin defects poses significant clinical challenges including risk of infection and severe scaring. Silver nanoparticle (NAg), an effective antimicrobial agent, has provided a promising therapeutic method for burn wounds. However, the detailed mechanism remains unknown. Hence, we constructed a metallic nanosilver particles-collagen/chitosan hybrid scaffold (NAg-CCS) and investigated its potential effects on wound healing.
In vitro
scratch assay, immunofluorescence staining and antibacterial activity of the scaffold were all studied.
In vivo
NAg-CCS was applied in full-thickness skin defects in Sprague-Dawley (SD) rats and the therapeutic effects of treatment were evaluated. The results showed that NAg at a concentration of 10 ppm accelerated the migration of fibroblasts with an increase in expression of α-smooth muscle actin (α-SMA). Furthermore,
in vivo
studies showed increased levels of pro-inflammatory and scar-related factors as well as α-SMA, while markers for macrophage activation were up-regulated. On day 60 post transplantation of ultra-thin skin graft, the regenerated skin by NAg-CCS had a similar structure to normal skin. In summary, we demonstrated that NAg-CCS was bactericidal, anti-inflammatory and promoted wound healing potentially by regulating fibroblast migration and macrophage activation, making it an ideal dermal substitute for wound regeneration.
Journal Article
Scaffolding in tissue engineering: general approaches and tissue-specific considerations
Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example.
Journal Article
Applications of bacterial cellulose and its composites in biomedicine
Bacterial cellulose produced by few but specific microbial genera is an extremely pure natural exopolysaccharide. Besides providing adhesive properties and a competitive advantage to the cellulose over-producer, bacterial cellulose confers UV protection, ensures maintenance of an aerobic environment, retains moisture, protects against heavy metal stress, etc. This unique nanostructured matrix is being widely explored for various medical and nonmedical applications. It can be produced in various shapes and forms because of which it finds varied uses in biomedicine. The attributes of bacterial cellulose such as biocompatibility, haemocompatibility, mechanical strength, microporosity and biodegradability with its unique surface chemistry make it ideally suited for a plethora of biomedical applications. This review highlights these qualities of bacterial cellulose in detail with emphasis on reports that prove its utility in biomedicine. It also gives an in-depth account of various biomedical applications ranging from implants and scaffolds for tissue engineering, carriers for drug delivery, wound-dressing materials, etc. that are reported until date. Besides, perspectives on limitations of commercialisation of bacterial cellulose have been presented. This review is also an update on the variety of low-cost substrates used for production of bacterial cellulose and its nonmedical applications and includes patents and commercial products based on bacterial cellulose.
Journal Article