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Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

Two‐dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well‐defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in Biology [ABSTRACT FROM AUTHOR]

Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided. [ABSTRACT FROM AUTHOR]

Converting biopolymers to extracellular matrix (ECM)‐mimetic hydrogel‐based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their ECM‐mimetic properties. Recently, we have developed the first class of in situ forming GelMA microporous hydrogels based on the chemical annealing of physically crosslinked GelMA microscale beads (microgels), which addressed several key shortcomings of bulk (nanoporous) GelMA scaffolds, including lack of interconnected micron‐sized pores to support on‐demand three‐dimensional‐cell seeding and cell–cell interactions. Here, we address one of the limitations of in situ forming microporous GelMA hydrogels, that is, the thermal instability (melting) of their physically crosslinked building blocks at physiological temperature, resulting in compromised microporosity. To overcome this challenge, we developed a two‐step fabrication strategy in which thermostable GelMA microbeads were produced via semi‐photocrosslinking, followed by photo‐annealing to form stable microporous scaffolds. We show that the semi‐photocrosslinking step (exposure time up to 90 s at an intensity of ~100 mW/cm2 and a wavelength of ~365 nm) increases the thermostability of GelMA microgels while decreasing their scaffold forming (annealing) capability. Hinging on the tradeoff between microgel and scaffold stabilities, we identify the optimal crosslinking condition (exposure time ~60 s) that enables the formation of stable annealed microgel scaffolds. This work is a step forward in engineering in situ forming microporous hydrogels made up from thermostable GelMA microgels for in vitro and in vivo applications at physiological temperature well above the gelatin melting point. [ABSTRACT FROM AUTHOR]

Next generation engineered tissue constructs with complex and ordered architectures aim to better mimic the native tissue structures, largely due to advances in 3D bioprinting techniques. Extrusion bioprinting has drawn tremendous attention due to its widespread availability, cost‐effectiveness, simplicity, and its facile and rapid processing. However, poor printing resolution and low speed have limited its fidelity and clinical implementation. To circumvent the downsides associated with extrusion printing, microfluidic technologies are increasingly being implemented in 3D bioprinting for engineering living constructs. These technologies enable biofabrication of heterogeneous biomimetic structures made of different types of cells, biomaterials, and biomolecules. Microfluiding bioprinting technology enables highly controlled fabrication of 3D constructs in high resolutions and it has been shown to be useful for building tubular structures and vascularized constructs, which may promote the survival and integration of implanted engineered tissues. Although this field is currently in its early development and the number of bioprinted implants is limited, it is envisioned that it will have a major impact on the production of customized clinical‐grade tissue constructs. Further studies are, however, needed to fully demonstrate the effectiveness of the technology in the lab and its translation to the clinic. [ABSTRACT FROM AUTHOR]

Tissue engineering approaches, with the goals of replacing or recovering damaged or diseased tissues, or of reconstituting tissues in vitro for disease modeling and drug development, have the potential to make significant contributions to medicine. Advances in stem cell biology, biomaterial synthesis and characterization, and microscale technologies have made engineered tissues a reality. However, the classic tools used to build tissues in the lab do not allow for complete control of cell behaviors. More recently, synthetic biology principles have developed robust and versatile approaches to program cells with artificial genetic circuits, where cell behavior and function can be manipulated. At the interface between synthetic biology and tissue engineering, there is space for a new area of investigation where material engineering and cellular engineering complement and sustain each other. In this progress report, synthetic biology principles and how they have been used to engineer cells with potential to dictate cell behavior and function in tissue constructs of the future are briefly described. It is believed that this research area still needs further exploration to fully exploit synthetic biology to make smart and functional cellular constructs for therapeutic and in vitro applications. [ABSTRACT FROM AUTHOR]

Gelatin is a promising material as scaffold with therapeutic and regenerative characteristics due to its chemical similarities to the extracellular matrix (ECM) in the native tissues, biocompatibility, biodegradability, low antigenicity, cost‐effectiveness, abundance, and accessible functional groups that allow facile chemical modifications with other biomaterials or biomolecules. Despite the advantages of gelatin, poor mechanical properties, sensitivity to enzymatic degradation, high viscosity, and reduced solubility in concentrated aqueous media have limited its applications and encouraged the development of gelatin‐based composite hydrogels. The drawbacks of gelatin may be surmounted by synergistically combining it with a wide range of polysaccharides. The addition of polysaccharides to gelatin is advantageous in mimicking the ECM, which largely contains proteoglycans or glycoproteins. Moreover, gelatin–polysaccharide biomaterials benefit from mechanical resilience, high stability, low thermal expansion, improved hydrophilicity, biocompatibility, antimicrobial and anti‐inflammatory properties, and wound healing potential. Here, we discuss how combining gelatin and polysaccharides provides a promising approach for developing superior therapeutic biomaterials. We review gelatin–polysaccharides scaffolds and their applications in cell culture and tissue engineering, providing an outlook for the future of this family of biomaterials as advanced natural therapeutics. [ABSTRACT FROM AUTHOR]

Keratins extracted from human hair have emerged as a promising biomaterial for various biomedical applications, partly due to their wide availability, low cost, minimal immune response, and the potential to engineer autologous tissue constructs. However, the fabrication of keratin-based scaffolds typically relies on limited crosslinking mechanisms, such as via physical interactions or disulfide bond formation, which are time-consuming and result in relatively poor mechanical strength and stability. Here, we report the preparation of photocrosslinkable keratin-polyethylene glycol (PEG) hydrogels via the thiol-norbornene "click" reaction, which can be formed within one minute upon irradiation of visible light. The resulting keratin-PEG hydrogels showed highly tunable mechanical properties of up to 45 kPa in compressive modulus, and long-term stability in buffer solutions and cell culture media. These keratin-based hydrogels were tested as cell culture substrates in both two-dimensional surface seeding and three-dimensional cell encapsulation, demonstrating excellent cytocompatibility to support the attachment, spreading, and proliferation of fibroblast cells. Moreover, the photocrosslinking mechanism makes keratin-based hydrogel suitable for various microfabrication techniques, such as micropatterning and wet spinning, to fabricate cell-laden tissue constructs with different architectures. We believe that the unique features of this photocrosslinkable human hair keratin hydrogel promise new opportunities for their future biomedical applications. [ABSTRACT FROM AUTHOR]

The host immune system is known to influence mesenchymal stem cell (MSC)-mediated bone tissue regeneration. However, the therapeutic capacity of hydrogel biomaterial to modulate the interplay between MSCs and T-lymphocytes is unknown. Here it is shown that encapsulating hydrogel affects this interplay when used to encapsulate MSCs for implantation by hindering the penetration of pro-inflammatory cells and/or cytokines, leading to improved viability of the encapsulated MSCs. This combats the effects of the host pro-inflammatory T-lymphocyte-induced nuclear factor kappaB pathway, which can reduce MSC viability through the CASPASE-3 and CASPASE-8 associated proapoptotic cascade, resulting in the apoptosis of MSCs. To corroborate rescue of engrafted MSCs from the insult of the host immune system, the incorporation of the anti-inflammatory drug indomethacin into the encapsulating alginate hydrogel further regulates the local microenvironment and prevents pro-inflammatory cytokine-induced apoptosis. These findings suggest that the encapsulating hydrogel can regulate the MSC-host immune cell interplay and direct the fate of the implanted MSCs, leading to enhanced tissue regeneration. [ABSTRACT FROM AUTHOR]

Engineering living tissues that simulate their natural counterparts is a dynamic area of research. Among the various models of biological tissues being developed, fiber-shaped cellular architectures, which can be used as artificial blood vessels or muscle fibers, have drawn particular attention. However, the fabrication of continuous microfiber substrates for culturing cells is still limited to a restricted number of polymers (e.g., alginate) having easy processability but poor cell-material interaction properties. Moreover, the typical smooth surface of a synthetic fiber does not replicate the micro- and nanofeatures observed in vivo, which guide and regulate cell behavior. In this study, a method to fabricate photocrosslinkable cell-responsive methacrylamide-modified gelatin (GelMA) fibers with exquisite microstructured surfaces by using a microfluidic device is developed. These hydrogel fibers with microgrooved surfaces efficiently promote cell encapsulation and adhesion. GelMA fibers significantly promote the viability of cells encapsulated in/or grown on the fibers compared with similar grooved alginate fibers used as controls. Importantly, the grooves engraved on the GelMA fibers induce cell alignment. Furthermore, the GelMA fibers exhibit excellent processability and could be wound into various shapes. These microstructured GelMA fibers have great potential as templates for the creation of fiber-shaped tissues or tissue microstructures. [ABSTRACT FROM AUTHOR]

Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable (PD) moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based PD hydrogels composed of methacrylated gelatin and a crosslinker containing o-nitrobenzyl ester groups are developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned PD hydrogels are shown to improve cell distribution, alignment, and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of PD hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function. [ABSTRACT FROM AUTHOR]

Carbon-based nanomaterials have been considered promising candidates to mimic certain structure and function of native extracellular matrix materials for tissue engineering. Significant progress has been made in fabricating carbon nanoparticle-incorporated cell culture substrates, but only a limited number of studies have been reported on the development of 3D tissue constructs using these nanomaterials. Here, a novel approach to engineer 3D multilayer constructs using layer-by-layer (LbL) assembly of cells separated with self-assembled graphene oxide (GO)-based thin films is presented. The GO-based structures are shown to serve as cell adhesive sheets that effectively facilitate the formation of multilayer cell constructs with interlayer connectivity. By controlling the amount of GO deposited in forming the thin films, the thickness of the multilayer tissue constructs could be tuned with high cell viability. Specifically, this approach could be useful for creating dense and tightly connected cardiac tissues through the co-culture of cardiomyocytes and other cell types. In this work, the fabrication of stand-alone multilayer cardiac tissues with strong spontaneous beating behavior and programmable pumping properties is demonstrated. Therefore, this LbL-based cell construct fabrication approach, utilizing GO thin films formed directly on cell surfaces, has great potential in engineering 3D tissue structures with improved organization, electrophysiological function, and mechanical integrity. [ABSTRACT FROM AUTHOR]

We introduce metallic glass thin films (TiCuNi) as biocompatible materials for biomedical applications. TiCuNi metallic glass thin films were deposited on the Si substrate and their structural, surface, and mechanical properties were investigated. The fabricated films showed good biocompatibility upon exposure to muscle cells. Also, they exhibited an average roughness of <0.2 nm, high wear resistance, and high mechanical properties (hardness ~6.9 GPa and reduced modulus ~130 GPa). Top surface of the TiCuNi films was shown to be free from Ni and mainly composed of a thin titanium oxide layer, which resulted in the high surface biocompatibility. In particular, there was no cytotoxicity effect of metallic glass films on the C2C12 myoblasts and the cells were able to proliferate well on these substrates. Low cost, viscoelastic behavior, patternability, high electrical conductivity, and the capability to coat various materials (e.g., nonbiocompatible materials) make TiCuNi as an attractive material for biomedical applications. [ABSTRACT FROM AUTHOR]

The fabrication of cell-laden structures with anisotropic mechanical properties while having a precise control over the distribution of different cell types within the constructs is important for many tissue engineering applications. Automated textile technologies for making fabrics allow simultaneous control over the color pattern and directional mechanical properties. The use of textile techniques in tissue engineering, however, demands the presence of cell-laden fibers that can withstand the mechanical stresses during the assembly process. Here, the concept of composite living fibers (CLFs) in which a core of load bearing synthetic polymer is coated by a hydrogel layer containing cells or microparticles is introduced. The core thread is drawn sequentially through reservoirs containing a cell-laden prepolymer and a crosslinking reagent. The thickness of the hydrogel layer increases linearly with to the drawing speed and the prepolymer viscosity. CLFs are fabricated and assembled using regular textile processes including weaving, knitting, braiding, winding, and embroidering, to form cell-laden structures. Cellular viability and metabolic activity are preserved during CLF fabrication and assembly, demonstrating the feasibility of using these processes for engineering functional 3D tissue constructs. [ABSTRACT FROM AUTHOR]

ABSTRACT Hydrogels mimic native tissue microenvironment due to their porous and hydrated molecular structure. An emerging approach to reinforce polymeric hydrogels and to include multiple functionalities focuses on incorporating nanoparticles within the hydrogel network. A wide range of nanoparticles, such as carbon-based, polymeric, ceramic, and metallic nanomaterials can be integrated within the hydrogel networks to obtain nanocomposites with superior properties and tailored functionality. Nanocomposite hydrogels can be engineered to possess superior physical, chemical, electrical, and biological properties. This review focuses on the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we discuss synthesis and fabrication of nanocomposite hydrogels, examine their current limitations and conclude with future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications. Biotechnol. Bioeng. 2014;111: 441-453. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Due to the increasing demand to generate thick and vascularized tissue-engineered constructs, novel strategies are currently being developed. An emerging example is the generation of oxygen-releasing biomaterials to tackle mass transport and diffusion limitations within engineered tissue constructs. Biomaterials containing oxygen-releasing molecules can be fabricated in various forms, such as hybrid thin films, microparticles or three dimensional scaffolds. In this perspective, we summarize various oxygen-releasing reagents and their potential applications in regenerative engineering. Moreover, we review the main approaches for fabricating oxygen-releasing biomaterials for a range of tissue engineering applications. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The article presents the developments made in thermoresponsive platforms for use in tissue engineering and regenerative medicine. Focus of the study is the action of poly(N-isopropylacrylamide) or PNIPAAm. The characteristics of PNIPAAm and the methods to create coated substrates, cell adhesion and detachment of tissues as well as recovery of cell-sheets are explained. Main use for 2-D and 3-D thermoresponsive templates are provided.

The article discusses the development of novel biomaterials that provide cells with a steady supply of oxygen and their use in various applications, including the regeneration of cardiac muscle after a heart attack. Topics include the challenges of creating vascularised tissues with a plentiful blood supply, the use of oxygen-releasing biomaterials for tissue engineering applications, and liquid and solid oxygen-releasing reagents, such as hydrogen peroxide (H2O2).

Tissue Engineering: Synthetic Biology and Tissue Engineering: Toward Fabrication of Complex and Smart Cellular Constructs (Adv. Funct. Keywords: material science; synthetic biology; tissue engineering EN material science synthetic biology tissue engineering 1 1 1 06/27/20 20200625 NES 200625 In article number 1909882, Samad Ahadian, Leonardo Morsut, Ali Khademhosseini, and co-workers highlight the great potential of tissue engineering approaches and synthetic biology principles to fabricate biological tissues and cellular constructs in a biomimetic and precise manner via the manipulation of cell behavior and function. Material science, synthetic biology, tissue engineering. [Extracted from the article]

An emerging approach to improve the physicobiochemical properties and the multifunctionality of biomaterials is to incorporate functional nanomaterials (NMs) onto 2D surfaces and into 3D hydrogel networks. This approach is starting to generate promising advanced functional materials such as self‐assembled monolayers (SAMs) and nanocomposite (NC) hydrogels of NMs with remarkable properties and tailored functionalities that are beneficial for a variety of biomedical applications, including tissue engineering, drug delivery, and developing biosensors. A wide range of NMs, such as carbon‐, metal‐, and silica‐based NMs, can be integrated into 2D and 3D biomaterial formulations due to their unique characteristics, such as magnetic properties, electrical properties, stimuli responsiveness, hydrophobicity/hydrophilicity, and chemical composition. The highly ordered nano‐ or microscale assemblies of NMs on surfaces alter the original properties of the NMs and add enhanced and/or synergetic and novel features to the final SAMs of the NM constructs. Furthermore, the incorporation of NMs into polymeric hydrogel networks reinforces the (soft) polymer matrix such that the formed NC hydrogels show extraordinary mechanical properties with superior biological properties. [ABSTRACT FROM AUTHOR]

A novel conductive bioink containing dispersed gold nanoparticles in a photocrosslinkable hydrogel matrix is developed for microfluidic bioprinting of cardiomyocyteladen microfibrous scaffolds. As described by Su Ryon Shin, Ali Khademhosseini, and co‐workers in article number 1605352, increased conductivity of the bioink leads to improved functionality of cardiomyocytes in the bioprinted patches, enabling potential applications in cardiac tissue engineering. [ABSTRACT FROM AUTHOR]