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.
Three‐dimensionally printed constructs are static and do not recapitulate the dynamic nature of tissues. Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed ...structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. The ability to make such dynamic constructs would enable an individual to fabricate tissue structures that can undergo morphological changes. Furthermore, other fields (bioactuation, biorobotics, and biosensing) will benefit from developments in 4D bioprinting. Here, the authors discuss stimuli‐responsive biomaterials as potential bioinks for 4D bioprinting. Natural cell forces can also be incorporated into 4D bioprinted structures. The authors introduce mathematical modeling to predict the transition and final state of 4D printed constructs. Different potential applications of 4D bioprinting are also described. Finally, the authors highlight future perspectives for this emerging technology in biomedicine.
Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. Here, different potential applications of 4D bioprinting are described.
This article is part of an AFOB (Asian Federation of Biotechnology) Special issue. To learn more about the AFOB visit www.afob.org.
Advances in biomaterial synthesis and fabrication, stem cell biology, bioimaging, microsurgery procedures, and microscale technologies have made minimally invasive therapeutics a viable tool in ...regenerative medicine. Therapeutics, herein defined as cells, biomaterials, biomolecules, and their combinations, can be delivered in a minimally invasive way to regenerate different tissues in the body, such as bone, cartilage, pancreas, cardiac, skeletal muscle, liver, skin, and neural tissues. Sophisticated methods of tracking, sensing, and stimulation of therapeutics in vivo using nano‐biomaterials and soft bioelectronic devices provide great opportunities to further develop minimally invasive and regenerative therapeutics (MIRET). In general, minimally invasive delivery methods offer high yield with low risk of complications and reduced costs compared to conventional delivery methods. Here, minimally invasive approaches for delivering regenerative therapeutics into the body are reviewed. The use of MIRET to treat different tissues and organs is described. Although some clinical trials have been performed using MIRET, it is hoped that such therapeutics find wider applications to treat patients. Finally, some future perspective and challenges for this emerging field are highlighted.
Current and future minimally invasive and regenerative therapeutics are reviewed together with delivery routes and tools. Regenerative therapeutics based on cells, biomaterials, biomolecules, and their combinations for different organs are described. The integration of minimally invasive approaches with robotics, regenerative therapeutics, and imaging techniques is also introduced. In addition, related challenges and future directions are discussed.
There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a ...research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe‐injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room‐temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large‐scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room‐temperature‐formed PEDOT:PSS hydrogels (RT‐PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self‐healable hydrogel bioelectronic devices.
A poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) suspension forms hydrogel at room temperature after being mixed with surfactants. Taking advantage of these room‐temperature formed hydrogels, various applications are presented including injectable conducting fillers, injectable conducting microfibers, and water‐healable conductors. These new demonstrations encourage further development of PEDOT:PSS hydrogels for potential biomedical applications.
Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic ...and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold's shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.
Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as ...organ‐on‐a‐chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.
Due to the significant advances in biomaterial synthesis, cell biology, and microscale technologies, personalized organ‐on‐a‐chip (OOC) platforms have emerged as a powerful tool in disease modeling for drug discovery and prediction. Here, several OOC platforms fabricated using biomaterials, cells, and microscale technologies are described. Major challenges and perspectives in the development of physiologically relevant OOC platforms are then highlighted.
Dielectrophoresis is used to align carbon nanotubes (CNTs) within gelatin methacrylate (GelMA) hydrogels in a facile and rapid manner. Aligned GelMA‐CNT hydrogels show higher electrical properties ...compared with pristine and randomly distributed CNTs in GelMA hydrogels. The muscle cells cultured on these materials demonstrate higher maturation compared with cells cultured on pristine and randomly distributed CNTs in GelMA hydrogels.
Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a ...minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
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•Collagen V deficiency increases scar size after acute heart injury•Mechanical properties of scars are altered with Col V deficiency•Altered mechanosensitive cues augment myofibroblast formation in scar•Inhibition of specific integrins rescues increased scarring in Col-V-deficient states
Scar tissue size following heart injury is a predictor of cardiovascular outcomes. Yokota et al. find that a specific collagen, type V, plays a paradoxical role in limiting scar size by altering the mechanical properties of developing scar tissue.
Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules, such as bone morphogenetic proteins, are desired for bone regeneration. Herein, we ...report the development of mesoporous silica rods with large cone-shaped pores (MSR-CP) to load and deliver large protein drugs. It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage. Furthermore, bone morphogenetic proteins 2 (BMP-2) loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.
In vivo
tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance. This study provides a potential strategy for the design of drug delivery systems for bone regeneration.
Electrical impulse generation and its conduction within cells or cellular networks are the cornerstone of electrophysiology. However, the advancement of the field is limited by sensing accuracy and ...the scalability of current recording technologies. Here we describe a scalable platform that enables accurate recording of transmembrane potentials in electrogenic cells. The platform employs a three-dimensional high-performance field-effect transistor array for minimally invasive cellular interfacing that produces faithful recordings, as validated by the gold standard patch clamp. Leveraging the high spatial and temporal resolutions of the field-effect transistors, we measured the intracellular signal conduction velocity of a cardiomyocyte to be 0.182 m s
, which is about five times the intercellular velocity. We also demonstrate intracellular recordings in cardiac muscle tissue constructs and reveal the signal conduction paths. This platform could provide new capabilities in probing the electrical behaviours of single cells and cellular networks, which carries broad implications for understanding cellular physiology, pathology and cell-cell interactions.
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