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Concept: Tissue engineering


Three-dimensional biomimetic scaffolds have widespread applications in biomedical tissue engineering because of their nanoscaled architecture, eg, nanofibers and nanopores, similar to the native extracellular matrix. In the conventional “top-down” approach, cells are seeded onto a biocompatible and biodegradable scaffold, in which cells are expected to populate in the scaffold and create their own extracellular matrix. The top-down approach based on these scaffolds has successfully engineered thin tissues, including skin, bladder, and cartilage in vitro. However, it is still a challenge to fabricate complex and functional tissues (eg, liver and kidney) due to the lack of vascularization systems and limited diffusion properties of these large biomimetic scaffolds. The emerging “bottom-up” method may hold great potential to address these challenges, and focuses on fabricating microscale tissue building blocks with a specific microarchitecture and assembling these units to engineer larger tissue constructs from the bottom up. In this review, state-of-the-art methods for fabrication of three-dimensional biomimetic scaffolds are presented, and their advantages and drawbacks are discussed. The bottom-up methods used to assemble microscale building blocks (eg, microscale hydrogels) for tissue engineering are also reviewed. Finally, perspectives on future development of the bottom-up approach for tissue engineering are addressed.

Concepts: Extracellular matrix, Engineering, Tissues, Tissue engineering, Tissue, Biomedical engineering, Top-down and bottom-up design, Software development process


Functional polysaccharides can be derived from plants (including herbs), animals and microorganisms. They have been widely used in a broad of biomedical applications, such as immunoregulatory agents or drug delivery vehicles. In the past few years, increasing studies have started to develop natural polysaccharides-based biomaterials for various applications in tissue engineering and regenerative medicine.

Concepts: Medicine, Eukaryote, Extracellular matrix, Fungus, Biotechnology, Engineering, Tissue engineering, Biomedical engineering


There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson’s Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.

Concepts: Immune system, Blood, Extracellular matrix, Immunology, Histology, Biomaterial, Biocompatibility, Tissue engineering


Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

Concepts: Wound healing, Extracellular matrix, Angiogenesis, Cell biology, Liver, Cellular differentiation, Platelet, Tissue engineering


Selective Laser Sintering (SLS) is an additive manufacturing process that uses a laser to fuse powdered starting materials into solid 3D structures. Despite the potential for fabrication of complex, high-resolution structures with SLS using diverse starting materials (including biomaterials), prohibitive costs of commercial SLS systems have hindered the wide adoption of this technology in the scientific community. Here, we developed a low-cost, open-source SLS system (OpenSLS) and demonstrated its capacity to fabricate structures in nylon with sub-millimeter features and overhanging regions. Subsequently, we demonstrated fabrication of polycaprolactone (PCL) into macroporous structures such as a diamond lattice. Widespread interest in using PCL for bone tissue engineering suggests that PCL lattices are relevant model scaffold geometries for engineering bone. SLS of materials with large powder grain size (~500 μm) leads to part surfaces with high roughness, so we further introduced a simple vapor-smoothing technique to reduce the surface roughness of sintered PCL structures which further improves their elastic modulus and yield stress. Vapor-smoothed PCL can also be used for sacrificial templating of perfusable fluidic networks within orthogonal materials such as poly(dimethylsiloxane) silicone. Finally, we demonstrated that human mesenchymal stem cells were able to adhere, survive, and differentiate down an osteogenic lineage on sintered and smoothed PCL surfaces, suggesting that OpenSLS has the potential to produce PCL scaffolds useful for cell studies. OpenSLS provides the scientific community with an accessible platform for the study of laser sintering and the fabrication of complex geometries in diverse materials.

Concepts: Stem cell, Mesenchymal stem cell, Bone marrow, Tissue engineering, Materials science, Sintering, Selective laser sintering, Additive manufacturing


Tissue engineering has been a promising field of research, offering hope for bridging the gap between organ shortage and transplantation needs. However, building three-dimensional (3D) vascularized organs remains the main technological barrier to be overcome. Organ printing, which is defined as computer-aided additive biofabrication of 3D cellular tissue constructs, has shed light on advancing this field into a new era. Organ printing takes advantage of rapid prototyping (RP) technology to print cells, biomaterials, and cell-laden biomaterials individually or in tandem, layer by layer, directly creating 3D tissue-like structures. Here, we overview RP-based bioprinting approaches and discuss the current challenges and trends towards fabricating living organs for transplant in the near future.

Concepts: Extracellular matrix, Organelle, Organ, Biomaterial, Biocompatibility, Tissue engineering, Skin, Organ transplant


A new combination of tissue engineering techniques provides a simple and effective method for building aligned cellular biomaterials. Self-alignment of Schwann cells within a tethered type-1 collagen matrix, followed by removal of interstitial fluid produces a stable tissue-like biomaterial that recreates the aligned cellular and extracellular matrix architecture associated with nerve grafts. Sheets of this engineered neural tissue supported and directed neuronal growth in a co-culture model, and initial in vivo tests showed that a device containing rods of rolled-up sheets could support neuronal growth during rat sciatic nerve repair (5 mm gap). Further testing of this device for repair of a critical-sized 15 mm gap showed that, at 8 weeks, engineered neural tissue had supported robust neuronal regeneration across the gap. This is, therefore, a useful new approach for generating anisotropic engineered tissues, and it can be used with Schwann cells to fabricate artificial neural tissue for peripheral nerve repair.

Concepts: Nervous system, Extracellular matrix, Action potential, Biomaterial, Biocompatibility, Tissue engineering, Axon, Myelin


Background  The mostly widely studied biomaterials for the sphincter sparing treatment of anal fistulas are fibrin glue and the anal fistula plug (AFP). However their overall mean clinical success is only 50-60%. As the understanding of the pathology of anal fistula, wound healing and the host response to materials has improved, so new biological sphincter-sparing strategies have been developed. The aim of this review is to assess the safety and efficacy of these novel techniques. Method  PubMed, the Cochrane database and EMBASE were independently searched. All studies that investigated the potential of a biomaterial (defined as any synthetic or biologically derived substance in contact with host tissue) to augment the healing of anal fistula without sphincter division were included. Studies solely describing the role of fibrin glue or an AFP were excluded. Data extraction included type of material, fistula aetiology, treatment of the primary tract, fistula healing, incontinence, duration of follow-up and any specific complications. Systematic quality assessment of the included articles was performed. Results  Twenty-three articles were finally selected for review. These included a variety of biological and synthetic systems that were employed to deliver selected components of the extracellular matrix, growth factors, cytokines, stem cells or drugs to the fistula tract. Conclusion  To date no study matches fistulotomy with regard to long-term fistula eradication rate. This is probably due to implant extrusion, inadequate track preparation or an unsuitable material. Future techniques need to address all these issues to ensure success. Success should be validated by MRI or long-term follow-up.

Concepts: Wound healing, Extracellular matrix, Angiogenesis, Tissue engineering, Materials science, Novel, Fistula, Anal fistula


Abstract Aim. The aim of this study was to compare the osteoconductivity and suitability of three biomaterials used as particulate fillers; S53P4 bioactive glass, allogeneic fresh frozen bone and coral-derived calcium carbonate. Materials and methods. Materials were implanted into drill-holes in the femoral condyles of adult rabbits. Follow-ups were performed at 3, 6, 12 and 24 weeks. Host-response, osteoconductivity, bonding and filler-effect were evaluated by SEM, EDXA and histology and histomorphometry to evaluate. Results. All three materials were found to be biocompatible and osteoconductive. Defects filled with allograft seemed to have more bone at 24 weeks, although no statistically significant difference in new bone growth was found. In earlier time points, coral, however, was observed to degrade more quickly, leaving more empty space in the defects, thus making it a less suitable filler for cavitary defects. Conclusion. At all time points there was less filler material (i.e. biomaterial and new bone) in coral-filled defects than in BAG or allograft filled defects (p < 0.05).

Concepts: Statistical significance, Calcium, Biomaterial, Biocompatibility, Tissue engineering, Materials science, Calcium carbonate, Materials


Bone is a nanocomposite composed of organic (mainly collagen) and inorganic (nanocrystalline hydroxyapatite) components, with a hierarchical structure ranging from nano- to macroscale. Its functions include providing mechanical support and transmitting physio-chemical and mechano-chemical cues. Clinical repair and reconstruction of bone defects has been conducted using autologous and allogeneic tissues and alloplastic materials, with functional limitations. The design and development of biomaterial scaffolds that will replace the form and function of native tissue while promoting regeneration without necrosis or scar formation is a challenging area of research. Nanomaterials and nanocomposites are promising platforms to recapitulate the organization of natural extracellular matrix for the fabrication of functional bone tissues because nanostructure provides a closer approximation to native bone architecture. Nanostructured scaffolds provide structural support for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. Unique properties of nanomaterials, such as increased wettability and surface area, lead to increased protein adsorption when compared with conventional biomaterials. Cell-scaffold interactions at the cell-material nanointerface may be mediated by integrin-triggered signaling pathways that affect cell behavior. The materials selection and processing techniques can affect the chemical, physical, mechanical, and cellular recognition properties of biomaterials. In this article, we focused on reviewing current fabrication techniques for nanomaterials and nanocomposites, their cell interaction properties and their application in bone tissue engineering and regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.

Concepts: Bone, Collagen, Extracellular matrix, Nanomaterials, Tissue engineering, Materials science, Tissue, Nanocomposite