Functional carbon-based nanomaterials (CBNs) have become important due to their unique combinations of chemical and physical properties (i.e., thermal and electrical conductivity, high mechanical ...strength, and optical properties), and extensive research efforts are being made to utilize these materials for various industrial applications, such as high-strength materials and electronics. These advantageous properties of CBNs are also actively investigated in several areas of biomedical engineering. This Perspective highlights different types of carbon-based nanomaterials currently used in biomedical applications.
Hydrogels are hydrophilic polymer‐based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel ...systems are used for a wide range of biomedical applications, such as three‐dimensional (3D) matrices for tissue engineering, drug‐delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.
Recent advances in the design of hydrogels with tunable physiochemical and biological properties and their potential applications in regenerative medicine are discussed, along with emerging technologies developed over the past decade to control the micro‐ and nanoscale architectures of three‐dimensional hydrogels for clinical use.
Microfabrication technology has emerged as a valuable tool for fabricating structures with high resolution and complex architecture for tissue engineering applications. For this purpose, it is ...imperative to develop “bioink” that can be readily converted to a solid structure by the modus operandi of a chosen apparatus, while optimally supporting the biological functions by tuning their physicochemical properties. Herein, a photocrosslinkable hyperbranched polyglycerol (acrylic hyperbranched glycerol (AHPG)) is developed as a crosslinker to fabricate cell‐laden hydrogels. Due to its hydrophilicity as well as numerous hydroxyl groups for the conjugation of reactive functional groups (e.g., acrylate), the mechanical properties of resulting hydrogels could be controlled in a wide range by tuning both molecular weight and degree of acrylate substitution of AHPG. The control of mechanical properties by AHPG is highly dependent on the type of monomer, due to the hydrophilic/hydrophobic balance of polyglycerol backbone and acrylate as well as the dynamic conformational flexibility based on the molecular weight of polyglycerol. The cell encapsulation studies demonstrate the biocompatibility of the AHPG‐linked hydrogels. Eventually, the AHPG‐based hydrogel precursor solution is employed as a bioink for a digital light processing based printing system to generate cell‐laden microgels with various shapes and sizes for tissue engineering applications.
A versatile bioink material that allows the control of hydrogel mechanics is developed using a photocrosslinkable hyperbranched polymer. By controlling the physical parameters of the hyperbranched polymer‐based bioink, the resulting hydrogels fabricated via light‐based printing show varying degrees and ranges of mechanics depending on different monomers, while maintaining biocompatibility and consistent shear‐thinning fluid behavior of the bioink.
With the recent advancement in emerging biomedical engineering fields, such as tissue engineering, regenerative medicine, and wearable medical devices, there is a growing need to develop adhesives ...that can function not only as tissue sealants for surgery and wound closure, but also attach various biomaterials and devices. These “bioadhesives” should allow refined control of cohesive and adhesive properties, while significantly improving the biocompatibility and biodegradability. For this reason, bioadhesives are being developed using a wide range of natural biopolymers with proven biocompatibility that can also impart multifunctionality either using their innate properties and/or obtained via various chemical modifications. In this review, state-of-the-art bioadhesives made from multifunctional biopolymers are introduced.
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Natural biopolymers are increasingly utilized to develop adhesives for biomedical applications, including wound healing and biomedical devices, for their favorable physicomechanical properties as well as their proven biocompatibility. Furthermore, various modification strategies are often employed to impart multifunctionality. In this review, recent development and notable examples of bioadhesives based on multifunctional biopolymers are highlighted.
Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as ...well as basic scientific endeavors, as several cell types can efficiently form spheroids by themselves in both suspension and adherent cell cultures. However, it is more desirable to utilize a 3D scaffold with tunable properties to create more physiologically relevant tumor spheroids as well as optimize their formation. In this study, bioactive spherical microgels supporting 3D cell culture are fabricated by a flow-focusing microfluidic device. Uniform-sized aqueous droplets of gel precursor solution dispersed with cells generated by the microfluidic device are photocrosslinked to fabricate cell-laden microgels. Their mechanical properties are controlled by the concentration of gel-forming polymer. Using breast adenocarcinoma cells, MCF-7, the effect of mechanical properties of microgels on their proliferation and the eventual spheroid formation was explored. Furthermore, the tumor cells are co-cultured with macrophages of fibroblasts, which are known to play a prominent role in tumor physiology, within the microgels to explore their role in spheroid formation. Taken together, the results from this study provide the design strategy for creating tumor spheroids utilizing mechanically-tunable microgels as 3D cell culture platform.
•Theranostic approach is considered a future paradigm of nanomedicine.•Theranostic nanomedicine efficiently combines therapeutic and diagnostic functions.•Carbon nanomaterials have a diverse array of ...chemical and physical properties.•With this versatility, they are actively investigated as theranostic agents.
Theranostic nanomedicine, utilizing state-of-the-art, multifaceted nanomaterials and devices with therapeutic and diagnostic dual functions, has emerged as a highly attractive and promising new field of medicine. The theory behind the use of nanomaterials for theranostic applications is to impart multifunctionality by applying various engineering strategies to combine different modalities on a nanoscale. Carbon nanomaterials, which have been a subject of intense scientific research and industrial applications in recent years, have also found their way into theranostic nanomedicine owing to their innate multifunctionality. In this review, we outline recent research progress and trends in utilizing various types of carbon nanomaterial for theranostic applications.
Remarkable advancement in 3D printing technology in recent years has already transformed many aspects of industrial manufacturing. The immense potential of 3D printing is already being explored in ...state-of-the-art biomedical research field. Often termed “bioprinting”, 3D printing is utilized to generate biological structures with high resolution and specificity for tissue engineering and regenerative medical applications. With the maturation of bioprinting apparatus, now the focus is shifting to engineering “bioinks” that can accommodate the versatility of biological systems, while still maintaining their printability. In this review, bioink technologies based on various polymers to produce soft biomaterials, such as hydrogels and elastomers, having a diverse array of physicochemical and bioactive properties are introduced and highlighted.
Hydrogels capable of stimuli-responsive deformation are widely explored as intelligent actuators for diverse applications. It is still a significant challenge, however, to "program" these hydrogels ...to undergo highly specific and extensive shape changes with precision, because the mechanical properties and deformation mechanism of the hydrogels are inherently coupled. Herein, two engineering strategies are simultaneously employed to develop thermoresponsive poly(N-isopropyl acrylamide) (PNIPAm)-based hydrogels capable of programmable actuation. First, PNIPAm is copolymerized with poly(ethylene glycol) diacrylate (PEGDA) with varying molecular weights and concentrations. In addition, graphene oxide (GO) or reduced graphene oxide (rGO) is incorporated to generate nanocomposite hydrogels. These strategies combine to allow the refined control of mechanical and diffusional properties of hydrogels over a broad range, which also directly influences variable thermoresponsive actuation. It is expected that this comprehensive design principle can be applied to a wide range of hydrogels for programmable actuation.
Graphene‐based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, an approach is presented to covalently incorporate graphene oxide (GO) into hydrogels ...via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface‐grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre‐gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO‐GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, this approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO‐GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell‐laden hydrogels.
Methacrylate is chemically grafted on the graphene oxide (GO) surface. Higher concentrations of the resulting methacrylated graphene oxide (MeGO) can be stably dispersed and conjugated within the hydrogels which improved fracture strength as compared with GO. In addition, cells maintain high viability within MeGO‐linked hydrogels. Therefore, covalent incorporation of GO induces proper interfacial bonding between GO and the polymeric network, and ultimately improves the quality of cell‐laden hydrogels.
Thermoresponsive poly(N-isopropylacrylamide) (PNIPAm)-based hydrogels are widely investigated for their ability to alter their physical properties (e.g. dimensions, swelling/deswelling) in response ...to change in temperature. Despite extensive research efforts, it is still challenging to control various aspects of thermoresponsive physical properties of PNIPAm hydrogels in an efficient and comprehensive manner using conventional small molecular crosslinkers due to their limited solubility and functional groups. Herein, thermoresponsive swelling/deswelling behavior of PNIPAm hydrogels is tuned in a wide range by hydrophilic polymeric crosslinkers with varying chain lengths. The concentration and molecular weight of the poly(ethylene glycol) (PEG) crosslinker are varied to control the swelling/deswelling behavior, drug release, and lower critical solution temperature (LCST) of PNIPAm-PEG hydrogels. Compared with PNIPAm hydrogels crosslinked with a conventional small molecular crosslinker, N,N′-methylenebisacrylamide, greater degree and range of thermoresponsive swelling/deswelling as well as tunable LCST are demonstrated for PNIPAm-PEG hydrogels. In addition, more swelling-controlled PNIPAm-PEG hydrogels displayed more sustained and variable thermoresponsive drug release based on their crosslinking density, by modulating the hydrophobic transition of PNIPAm chains with hydrophilic PEG chains. In sum, various thermoresponsive properties of PNIPAm hydrogels could be controlled by hydrophilic polymeric crosslinkers, and this strategy could be applied to various hydrogel systems to control their physical properties for biomedical applications.
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