Review articleThe triad of nanotechnology, cell signalling, and scaffold implantation for the successful repair of damaged organs: An overview on soft-tissue engineering
Graphical abstract
Introduction
Organ implantation is restricted by the shortage of accessible donors and expensive processes, leaving numerous patients on transplant waiting lists, many of whom expire before receiving any organ [1]. Lately, tissue engineering has developed as an interdisciplinary field incorporating principles from engineering, material, and life sciences to enhance functional alternatives for injured organs and tissues [2]. Instead of incorporating cells into a defected part to regenerate a tissue and/or return its function, cells are typically embedded in or seeded onto biomaterials prior to transplantation [3]. These samples act as degradable scaffolds and redefine cellular rearrangements to create a functional tissue [4]. The macro-porous structure of the substrates applied in tissue regeneration imitates the conformational features of the matrix itself (artificial or natural). Extracellular matrix (ECM) acts as an appropriate cellular substrate, and morphogenesis is passively regulated by determining tissue boundaries [5]. For efficient tissue regeneration, well-designed engineering, enhancing mass transfer to the core of the tissue, and designing biodegradable and biocompatible platforms with proper mechanical characteristics for engineering different tissues are among the main concerns[6]. The role of scaffolds' biological properties in regulating the function of several types of cells has been suggested [7]. A problem in current tissue regeneration approaches is that most commonly used mats do not recapitulate tissues' microenvironments. This is important as ECM is a hierarchically and dynamically arranged nanocomposite structure that controls vital cellular functions such as migration, proliferation, morphogenesis, adhesion, and differentiation [8]. As a result, researchers are seeking novel nano-technological devices for tissue regeneration to provide innovative nanocomposite frameworks that can imitate ECMs and finally assemble larger and more complicated functional tissues [[9], [10], [11], [12]]. To explore the link between nanotechnology and tissue regeneration, we here first explain the nanostructure of ECMs and then explore its impacts on functional tissue properties. We also address various nano-scale based methods and materials for designing ECMs for different engineered tissues [13].
Nanomaterials have permitted tissue engineering substrates to represent higher mechanical strength and to improve cellular proliferation and differentiation [14]. Carbon-based nanomaterials, such as graphene oxide (GO) [15], fullerenes, carbon nanotubes (CNTs) [16], carbon dots (CDs) [17], graphene [18] composite scaffolds, and nanoparticles have attracted much attention in soft tissue engineering[19]. These materials have unique mechanical, dimensional, optical, and conductive features that provide new opportunities for enhanced soft tissue engineering. Several groups have established various functionalization techniques for carbonic nanomaterials to attain better biocompatibility, as well as cellular attachment capability and differentiation. Artificial cell substrates for soft tissue regeneration and healing are needed to be comparable with natural ECM structures in terms of mechanical properties, chemical composition, and physical properties. Moreover, the electrical conducting properties of carbon-based nanocomposite scaffolds can be applied to offer electrical cues to tissues [20,21].
Some conducting nanomaterials such as nanocomposite bioinks have been applied for biofabrication purposes. For example, bioactive DNA-coated single-wall CNT is a conductive bioink used for three-dimensional (3D) printing of conductive flexible electronics via a two-step procedure on various supportive platforms [22]. A 3D-printed model of “cardiac organs-on-chip” is another example of the applications of nanoinks (applying carbon black nanoparticles-laden thermoplastic poly urethane as a conductive ink in combination with other inks) [23]. The constructs printed in this manner have several features such as piezoresistivity, high conductance, and great biocompatibility. In another study, researchers used the nanoinks comprising graphene and poly(lactide-co-glycolide) (PLGA) for printing a 3D model of neuronal conduits to enhance neural regeneration [24]. Chief biopolymers for neural regeneration include polysaccharides, natural proteins, and ECM derivatives. Biocompatible materials are used for nerve conduits preparation. These materials serve as substrates for inducing cellular proliferation and delivering molecular signals during neural regeneration. Biocompatibility, mechanical compatibility, and histocompatibility are considered as essential factors for successful neural regeneration both in vivo and in vitro. Treatment with either oxygen or plasma can be used to synthesize polymers with weak protein adsorption capacities and acceptable biocompatibility. In this regard, laminin which has excellent biocompatibility, in association with chitosan and PLGA, has been shown to improve cells' adhesive and proliferative functions [25].
Moreover, nanomaterials can be used to boost the in vivo efficiency of growth factors along with extending their local release and protecting them from proteolytic degradation. A broad range of nano-delivery systems have been considered to improve wound healing, mostly nanofibrous structures, lipid NPs, and polymeric NPs. Recently, biocompatible polymeric systems have been investigated for optimizing the controlled release of biological compounds including growth factors [26,27]. The role of nanomedicine in tissue engineering has been summarized in Fig. 1, and some of the biomaterials commonly used in tissue engineering have been reviewed in Table 1. We will discuss the effects of nanostructures on scaffolds' features and their applications in controlling the attributes of engineered tissues. At the end, we provide some perspectives on the future of nanotechnology in tissue engineering and regeneration.
Section snippets
Skin tissue engineering
Acute dermal injuries such as serious burns and diabetic wounds, in which pathogens have sufficient time to colonize, are the salient causes of mortality around the world. Rapid closure of chronic wounds is crucial for the prevention of hypertrophic scarring. Appropriate coverage and rapid treatments are vital steps to prolong the survival of people with extensive burns and to avoid widespread scarring and long-term physiological defects. Using split thickness autografts, as a current therapy,
Nanomaterials in neural tissue engineering
Nerves form one of the vital systems of the body, and defects in these cells lead to significant morbidities and even mortality. According to annual American statistics, about 250,000–400,000 patients are buckled under neural diseases every year [172].
Nerves' gaps and neurons' injuries are claimed to be the main neural defects which couldn't be spontaneously restored by natural biological mechanisms. By means of tissue engineering, neural regeneration works out for neural repairing. The neural
Nanomaterials in ocular tissue engineering
Ocular tissue engineering focuses on the defects of three main parts including the cornea, lens, and stroma. Current therapies have limitations such as the shortage of donors, rejection, and inflammatory responses. Tissue engineering solves these problems and provides efficient therapies to regenerate synthetic and functional corneal prosthesis [265]; however, the clinical translation of this has not been yet proved. In this regard, as a troubleshooting approach, 3D bioprinting has been used to
Nanomaterials for liver tissue engineering
The liver is a vital organ in the body, and its disorders are among the main causes of mortality and morbidity worldwide. The aim of novel therapies is to replace the failed organ with functional in vitro models and alternatives as the shortage of donors and increasing drug-induced injuries have restricted the applicability of current transplantation methods [360]. The nature of cultured stem cells, scaffolds' properties (i.e., the type of constructed materials, porous structure, 3D design,
Conclusion
Using autografts and allografts to correct tissue injuries suffers from some limitations such as shortage of donors and unwanted inflammatory responses. As a novel alternative therapeutic method, tissue engineering has been widely studied to regenerate tissues. This approach aims to simulate natural organs both in vitro and in vivo. Cells are cultured on appropriate scaffolds and under specific growth factors to support their differentiation. The porous structures of scaffolds are essential for
Declaration of competing interest
The authors hereby declare that there was no conflict of interest in the present study.
Acknowledgments
The authors would like to thank Tabriz University of Medical Sciences, Tabriz, Iran and North Khorasan University of Medical Sciences, Bojnurd, Iran.
References (381)
- et al.
Bacterial-derived biopolymers: advanced natural nanomaterials for drug delivery and tissue engineering
TrAC Trends Anal. Chem.
(2016) - et al.
Boron-containing bioactive glasses in bone and soft tissue engineering
J. Eur. Ceram. Soc.
(2018) - et al.
Polysaccharide based scaffolds for soft tissue engineering applications
Polymers
(2019) - et al.
Recent advances in nanotechnology-based drug delivery systems for the kidney
J. Control. Release
(2020) - et al.
Efficient megalin targeted delivery to renal proximal tubular cells mediated by modified-polymyxin B-polyethylenimine based nano-gene-carriers
Mater. Sci. Eng. C
(2017) - et al.
Recent advances in the application of mesoporous silica-based nanomaterials for bone tissue engineering
Mater. Sci. Eng. C
(2020) - et al.
Composition and design of nanofibrous scaffolds of Mg/Se- hydroxyapatite/graphene oxide @ ε-polycaprolactone for wound healing applications
Biomed. Mater.
(2020) - et al.
Evaporation-driven 3D CNT scaffolding for composite reinforcement
Carbon
(2021) - et al.
Carbon dot/WS2 heterojunctions for NIR-II enhanced photothermal therapy of osteosarcoma and bone regeneration
Chem. Eng. J.
(2020) - et al.
Physical, electrochemical and biological evaluations of spin-coated ε-polycaprolactone thin films containing alumina/graphene/carbonated hydroxyapatite/titania for tissue engineering applications
Int. J. Pharm.
(2020)