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The concept of tissue-engineered heart valves offers an alternative to current heart valve replacements that is capable of addressing shortcomings such as life-long administration of anticoagulants, inadequate durability, and inability to grow. Since tissue engineering is a multifaceted area, studies conducted have focused on different aspects such as hemodynamics, cellular interactions and mechanisms, scaffold designs, and mechanical characteristics in the form of both in vitro and in vivo investigations. This review concentrates on the advancements of scaffold materials and manufacturing processes, and on cell–scaffold interactions. Aside from the commonly used materials, polyglycolic acid and polylactic acid, novel polymers such as hydrogels and trimethylene carbonate-based polymers are being developed to simulate the natural mechanical characteristics of heart valves. Electrospinning has been examined as a new manufacturing technique that has the potential to facilitate tissue formation via increased surface area. The type of cells utilized for seeding onto the scaffolds is another factor to take into consideration; currently, stem cells are of great interest because of their potential to differentiate into various types of cells. Although extensive studies have been conducted, the creation of a fully functional heart valve that is clinically applicable still requires further investigation due to the complexity and intricacies of the heart valve.

Fibers are structurally interesting components most useful in a range of applications spanning the physical and life science areas of research. These membrane (scaffold) forming fibers have been explored in applications ranging from microfilteration to advanced biological investigations in tissue engineering to controlled and targeted drug delivery. One such robust fiber generation approach investigated for over a century, which has recently been exploited, is the well-established threading process referred to as electrospinning. In this technique, single- or multi-phase media are charged within a conducting needle and later exposed to an electric field which promotes the formation of a continuous micro- to nanosized fiber(s) which over a period of collection time has been reported for forming scaffolds and membranes. This process has been explored for a wide range of polymer composite-based materials and the technique has now reached the point where it has moved into industrial production. We report here as a first example a comparable fiber to membrane fabrication approach completely driven by the coupling of a coaxial needle system with a pressure. We refer to this novel methodology as pressure-assisted spinning (PAS) where the hazardous element of high voltage (as in the case of electrospinning) is nonexistent. Hence, our discovery introduces both a directly competing fiber, scaffold to membrane fabrication approach, which is versatile and has no associated hazards as those in electrospinning. Furthermore as our technique is nonelectric field driven, the media spun into fibers could have a high electrical conductivity, which in this case has no effect on the stability in processing near-uniform fibers/scaffolds to membranes. The fabricated fibers and membranes generated by means of this approach could directly be used for a plethora of applications spanning the engineering and biological areas of research.

In this paper, we have developed self-assembled nanoscale assemblies that were prepared by conjugating furan-2-carboxylic acid-3-aminopropyl amide with the short peptide sequence Gly-His (abbreviated Gly-His-FCAP). To mimic the extracellular matrix of mammalian fibroblasts and keratinocytes, the assemblies were then conjugated with Type I collagen. We then integrated the collagen bound Gly-His-FCAP assemblies with a short peptide sequence derived from salamander skin into the nanoscale assemblies for the first time to impart regenerative and wound healing properties to the composites. The antioxidant, antimicrobial and biodegradable properties were examined and results indicate that the nanocomposites displayed antioxidant properties as displayed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The biodegradability was found to be gradual. The nanocomposites were also found to inhibit the growth of the fungus Rhizopus sporangia over an 18h growth period. As proof of concept, to demonstrate the development of three-dimensional (3D) engineered skin in vitro, 3D printed PLA scaffolds of 2.5mm thickness were submerged in media containing nanocomposites and co-cultures of dermal fibroblasts with epidermal keratinocytes mimicking three dimensional skin substitute was examined. Our results indicated that the nanocomposites adhered to and supported cell proliferation and mimicked the components of skin and may have potential applications in skin tissue regeneration.

Scaffolds offer a three-dimensional framework supporting cell growth, proliferation, and differentiation of cells which are used to repair and regenerate tissues. Recent advancements in scaffold technology have significantly exploited the field of tissue engineering and regenerative medicine. This comprehensive review provides in-depth exploration of scaffold materials, fabrication techniques, and their recent progress in applications. Composite scaffolds have promising applications in bone and dental tissue regeneration due to their greater mechanical properties and ability to promote cell growth. The inherent crosslinking present in hydrogels allows them to maintain their integrity and three-dimensional structure without dissolving. However, there is a growing interest in smart hydrogels which can respond to changes in their external surroundings like pH, ionic strength, temperature, or specific molecules. dECM scaffold is an alternative potential technique for reconstructing the functional organs/tissues by excluding the cell-associated antigens while maintaining the native ECM compositions like growth factors, basement membrane structural proteins, and GAG’s. The degree of porosity in scaffolds can be increased by various fabrication techniques such as TIPS, SCPL, gas foaming, and freeze drying. GelMA hydrogels have shown promising potential in cell proliferation and tissue regeneration. In addition, graphene and its derivatives have been instrumental in the fabrication of bioactive scaffolds for cartilage regeneration. The introduction of additive manufacturing technologies, specifically 3D bioprinting, has significantly improved the precision and control of scaffold fabrication.

In this work, we used multiphoton microscopic system for characterizing three-dimensional microstructure of collagen/chitosan polymeric scaffolds in a noninvasive fashion. Nonlinear optical signals including multiphoton autofluorescence (MAF) and second harmonic generation (SHG) derived from collagen/chitosan scaffolds were collected and analyzed. The three-dimensional porous microstructures of collagen/chitosan scaffolds were visualized by co-localized and evenly distributed MAF and SHG signals. The distribution of collagen and chitosan compositions within miscible collagen/chitosan blends cannot be either localized or differentiated simply using these nonlinear optical signals. However, the intensity of MAF signals in scaffolds was found to be markedly decreased in correlation to the supplementation of chitosan within blends, regardless of collagen/chitosan weight ratios. It therefore implied that the MAF-generating molecules within collagen being altered in miscible collagen/chitosan blends. And the SHG signals also decreased significantly in collagen/chitosan scaffolds with the supplementation of chitosan, regardless of different weight ratios. This finding supported the hypothesis regarding the miscibility of collagen/chitosan blends that triple helix structure of collagen, a proven SHG-generating microstructure, was altered in miscible collagen/chitosan blends. In conclusion, our work demonstrated that multiphoton imaging modality can be versatile for investigating three-dimensional microstructure of miscible polymeric scaffolds in a minimal invasive fashion, and may potentially be applicable in the field of tissue engineering.

Synthetic bioactive and bioresorbable composite materials are becoming increasingly important as scaffolds for bone tissue engineering. Next generation biomaterials should combine bioactive and bioresorbable properties to activate in vivo mechanisms of tissue regeneration, stimulating the body to heal itself and leading to replacement of the scaffold by the regenerating tissue. In the present chapter composite materials based on smart combinations of biodegradable polymers and bioactive ceramics, including hydroxyapatite and bioactive glasses, are discussed as suitable materials for scaffold fabrication. These composites exhibit tailored physical, biological and mechanical properties as well as predictable degradation behaviour. The appropriate selection of a particular composite for a given application requires a detailed understanding of relevant cells and/or tissue response. Knowledge concerning interactions between cells and their immediate local environment in composite scaffolds has deeply improved in the last years. An overview of these findings is presented highlighting the influence of material processing methods, scaffold microstructure as well as the importance of the nature and amount of the bioactive ceramic particulate included in specific polymer matrices. The chapter also emphasises the response diversity according to the cell type used in vitro or the chosen in vivo models (species and location), suggesting the utility of standardisation in this field of biomaterials science. Bioactive composites discussed in this chapter, enhanced by microstructural optimisation and surface engineering, are suggested as the materials of choice for development of optimal bone tissue engineering scaffolds.

In regenerative medicine it is important to be able to understand how cells are behaving in response to stimuli. The stimuli can be biological signals or materials. Raman spectroscopy allows the non-invasive real time monitoring of live cells in vitro by interpretation of spectra. Materials are being developed to use as templates (scaffolds) for tissue regeneration. The morphology of the pore structure is critical if tissue is to populate the scaffold. X-ray microcomputed tomography is the only method that can obtain 3D images of pore networks. Novel image analysis has been developed that can quantify pore networks. There is potential for this technique to be used to image tissue growth into scaffolds ex vivo. The next challenge is to adapt these two promising techniques to monitor the response of cells to porous scaffolds, including that of cells within the porous network.