Nanostructured Materials for Cardiovascular Tissue Engineering

Substantial progress has been made in the field of cardiovascular tissue engineering with an ever increasing number of clinically viable implants being reported. However, poor cellular integration of constructs remains a major problem. Limitations in our knowledge of cell/substrate interactions and their impact upon cell proliferation, survival and phenotype are proving to be a major hindrance. Advances in nanotechnology have allowed researchers to fabricate scaffolds which mimic the natural cell environment to a greater extent; allowing the elucidation of appropriate physical cues which influence cell behaviour. The ability to manipulate cell/substrate interactions at the micro/nano scale may help to create a viable cellular environment which can integrate effectively with the host tissue. This review summarises the influence of nanotopographical features on cell behaviour and provides details of some popular fabricating techniques to manufacture 3D scaffolds for tissue engineering. Recent examples of the translation of this research into fabricating clinically viable implants for the regeneration of cardiovascular tissues are also provided

Nanostructured Materials for Cardiovascular Tissue Engineering

Substantial progress has been made in the field of cardiovascular tissue engineering with an ever increasing number of clinically viable implants being reported. However, poor cellular integration of constructs remains a major problem. Limitations in our knowledge of cell/substrate interactions and their impact upon cell proliferation, survival and phenotype are proving to be a major hindrance. Advances in nanotechnology have allowed researchers to fabricate scaffolds which mimic the natural cell environment to a greater extent; allowing the elucidation of appropriate physical cues which influence cell behaviour. The ability to manipulate cell/substrate interactions at the micro/nano scale may help to create a viable cellular environment which can integrate effectively with the host tissue. This review summarises the influence of nanotopographical features on cell behaviour and provides details of some popular fabricating techniques to manufacture 3D scaffolds for tissue engineering. Recent examples of the translation of this research into fabricating clinically viable implants for the regeneration of cardiovascular tissues are also provided

Cell infiltrative hydrogel fibrous scaffolds for accelerated wound healing.

Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering

Photocrosslinkable gelatin hydrogel for epidermal tissue engineering

Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models

Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models

Cell infiltrative hydrogel fibrous scaffolds for accelerated wound healing

Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct a three-dimensional (3D), fully cellularized scaffold for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on methacryloylated gelatin (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA hydrogel fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings