Degradable Self-healable Networks for Use in Biomedical Applications

Among biomaterials, 3D networks with capacities to absorb and retain large quantities of water (hydrogels) or withstand significant deformation and stress while recovering their initial structures at rest (elastomers) are largely used in biomedical applications. However, when damaged, they cannot recover their initial structures and properties. To overcome this limitation and satisfy the requirements of the biomedical field, self-healable hydrogels and elastomers designed using (bio)degradable or bioeliminable polymer chains have been developed and are becoming increasingly popular. This review presents the latest advances in the field of self-healing degradable/bioeliminable networks designed for use in health applications. The strategies used to develop such networks based on reversible covalent or physical cross-linking or their combination via dual/multi-cross-linking approaches are analyzed in detail. The key parameters of these hydrogels and elastomers, such as mechanical properties, repair and degradation times, and healing efficiencies, are critically considered in terms of their suitabilities in biomedical applications. Finally, their current and prospective uses as biomaterials in the fields of tissue engineering, drug/cell delivery, and medical devices are presented, followed by the remaining challenges faced to ensure the further success of degradable self-healable networks.     

Magnetic Hydrogels and Their Potential Biomedical Applications

Hydrogels find widespread applications in biomedical engineering due to their hydrated environment and tunable properties (e.g., mechanical, chemical, biocompatible) similar to the native extracellular matrix (ECM). However, challenges still exist regarding utilizing hydrogels in applications such as engineering 3D tissue constructs and active targeting in drug delivery, due to the lack of controllability, actuation, and quick‐response properties. Recently, magnetic hydrogels have emerged as a novel biocomposite for their active response properties and extended applications. In this review, the state‐of‐the‐art methods for magnetic hydrogel preparation are presented and their advantages and drawbacks in applications are discussed. The applications of magnetic hydrogels in biomedical engineering are also reviewed, including tissue engineering, drug delivery and release, enzyme immobilization, cancer therapy, and soft actuators. Concluding remarks and perspectives for the future development of magnetic hydrogels are addressed.     

Hybrid functional microfibers for textile electronics and biosensors

Fibers are low-cost substrates that are abundantly used in our daily lives.This review highlights recent advances in the fabrication and application of multifunctional fibers to achieve fibers with unique functions for specific applications ranging from textile electronics to biomedical applications.By incorporating various nanomaterials such as carbon nanomaterials,metallic nanomaterials,and hydrogel-based biomaterials,the functions of fibers can be precisely engineered.This review also highlights the performance of the functional fibers and electronic materials incorporated with textiles and demonstrates their practical application in pressure/tensile sensors,chemical/biosensors,and drug delivery.Textile technologies in which fibers containing biological factors and cells are formed and assembled into constructions with biomimetic properties have attracted substantial attention in the field of tissue engineering.We also discuss the current limitations of functional textile-based devices and their prospects for use in various future applications.     

Fabrication of Architectured Biomaterials by Multilayer Co-Extrusion and Additive Manufacturing

Tissue engineering benefits from advances in 3D printing and multi-material assembly to attain certain functional benefits over existing man-made materials. Multilayered tissue engineering constructs might unlock a unique combination of properties, but their fabrication remains challenging. Herein, a facile process is reported to manufacture biomaterials with an engineered multilayer architecture, via a combination of co-extrusion and 3D printing. Polymer filaments containing 5, 17, or 129 alternating layers of poly(lactic acid)/thermoplastic polyurethane (PLA/TPU) are produced, and explored for their use in fused deposition modeling (FDM) to fabricate scaffolds for cardiomyocyte culture. The co-extruded filaments exhibit a layered architecture in their cross-section with a continuous interface, and the integrity and alignment of the layers are preserved after 3D printing. The 17 alternating layers PLA/TPU composites exhibit excellent mechanical properties. It is envisaged that the multilayered architecture of the fabricated scaffolds can be beneficial for aligning cardiomyocytes in culture. It is found that the 17 alternating layers PLA/TPU significantly improve cardiomyocyte morphology and functionality compared to single phase materials. It is believed that this biomaterials fabrication scheme, combining a top-down and bottom-up approach, offers tremendous flexibility in producing a broad class of novel-architectured materials with tunable structural design for tissue engineering applications and beyond.     

Nanoengineering Hybrid Supramolecular Multilayered Biomaterials Using Polysaccharides and Self‐Assembling Peptide Amphiphiles

Developing complex supramolecular biomaterials through highly dynamic and reversible noncovalent interactions has attracted great attention from the scientific community aiming key biomedical and biotechnological applications, including tissue engineering, regenerative medicine, or drug delivery. In this study, the authors report the fabrication of hybrid supramolecular multilayered biomaterials, comprising high‐molecular‐weight biopolymers and oppositely charged low‐molecular‐weight peptide amphiphiles (PAs), through combination of self‐assembly and electrostatically driven layer‐by‐layer (LbL) assembly approach. Alginate, an anionic polysaccharide, is used to trigger the self‐assembling capability of positively charged PA and formation of 1D nanofiber networks. The LbL technology is further used to fabricate supramolecular multilayered biomaterials by repeating the alternate deposition of both molecules. The fabrication process is monitored by quartz crystal microbalance, revealing that both materials can be successfully combined to conceive stable supramolecular systems. The morphological properties of the systems are studied by advanced microscopy techniques, revealing the nanostructured dimensions and 1D nanofibrous network of the assembly formed by the two molecules. Enhanced C2C12 cell adhesion, proliferation, and differentiation are observed on nanostructures having PA as outermost layer. Such supramolecular biomaterials demonstrate to be innovative matrices for cell culture and hold great potential to be used in the near future as promising biomimetic supramolecular nanoplatforms for practical applications.     

Functional Nanomaterials on 2D Surfaces and in 3D Nanocomposite Hydrogels for Biomedical Applications

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.     

Biomimetic Ultralight,Highly Porous,Shape‐Adjustable,and Biocompatible 3D Graphene Minerals via Incorporation of Self‐Assembled Peptide Nanosheets

Hybrid nanomaterials with tailored functions, consisting of self‐assembled peptides, are intensively applied in nanotechnology, tissue engineering, and biomedical applications due to their unique structures and properties. Herein, a peptide‐mediated biomimetic strategy is adopted to create the multifunctional 3D graphene foam (GF)‐based hybrid minerals. First, 2D peptide nanosheets (PNSs), obtained by self‐assembling a motif‐specific peptide molecule (LLVFGAKMLPHHGA), are expected to exhibit biofunctionality, such as the biomimetic mineralization of hydroxyapatite (HA) minerals. Subsequently, the noncovalent conjugation of PNSs onto GF support is utilized to form 3D GF‐PNSs hybrid scaffolds, which are suitable for the growth of HA minerals. The fabricated biomimetic 3D GF‐PNSs‐HA minerals exhibit adjustable shape, superlow weight (0.017 g cm^?3), high porosity (5.17 m² g^?1), and excellent biocompatibility, proving potential applications in both bone tissue engineering and biomedical engineering. To the best of the authors' knowledge, it is the first time to combine 2D PNSs and GF to fabricate 3D organic–inorganic hybrid scaffold. Further development of these hybrid GF‐PNSs scaffolds can potentially lead to materials used as matrices for drug delivery or bone tissue engineering as proven via successful 3D scaffold formation exhibiting interconnected pore‐size structures suitable for vascularization and medium transport.     

Single Cell Bioprinting with Ultrashort Laser Pulses

Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell-friendly, easy to use, and fast technologies for selecting and positioning mammalian cells with single cell precision are still in need. A new laser-based bioprinting approach is therefore presented, which allows the selection of individual cells from complex cell mixtures based on morphology or fluorescence and their transfer onto a 2D target substrate or a preprocessed 3D scaffold with single cell precision and high cell viability (93–99% cell survival, depending on cell type and substrate). In addition to precise cell positioning, this approach can also be used for the generation of 3D structures by transferring and depositing multiple hydrogel droplets. By further automating and combining this approach with other 3D printing technologies, such as two-photon stereolithography, it has a high potential of becoming a fast and versatile technology for the 2D and 3D bioprinting of mammalian cells with single cell resolution.     

Graphene-Based Nanomaterials for Neuroengineering: Recent Advances and Future Prospective

Graphene unique physicochemical properties made it prominent among other allotropic forms of carbon, in many areas of research and technological applications. Interestingly, in recent years, many studies exploited the use of graphene family nanomaterials (GNMs) for biomedical applications such as drug delivery, diagnostics, bioimaging, and tissue engineering research. GNMs are successfully used for the design of scaffolds for controlled induction of cell differentiation and tissue regeneration. Critically, it is important to identify the more appropriate nano/bio material interface sustaining cells differentiation and tissue regeneration enhancement. Specifically, this review is focussed on graphene-based scaffolds that endow physiochemical and biological properties suitable for a specific tissue, the nervous system, that links tightly morphological and electrical properties. Different strategies are reviewed to exploit GNMs for neuronal engineering and regeneration, material toxicity, and biocompatibility. Specifically, the potentiality for neuronal stem cells differentiation and subsequent neuronal network growth as well as the impact of electrical stimulation through GNM on cells is presented. The use of field effect transistor (FET) based on graphene for neuronal regeneration is described. This review concludes the important aspects to be controlled to make graphene a promising candidate for further advanced application in neuronal tissue engineering and biomedical use.     

Advanced Collagen‐Based Biomaterials for Regenerative Biomedicine

In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.     

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.     

Advanced Theragenerative Biomaterials with Therapeutic and Regeneration Multifunctionality

All tissues and organs can be affected by diseases, and treatments for these diseases can cause damage to surrounding healthy tissues and organs. Therefore, treatment is required that involves disease therapy alongside tissue/organ regeneration. The design, construction, and biomedical applications of biomaterial platforms with both disease‐therapeutic and tissue‐regeneration multifunctionalities are in demand, which are herein referred to as theragenerative (abbreviation of therapy and regeneration) biomaterials. Due to the rapid development of theragenerative biomaterials in versatile biomedical applications, this progress report aims to summarize, discuss, and highlight the rational construction of distinctive theragenerative biomaterials with intrinsic therapeutic performance and tissue‐regeneration bioactivity. Based on the intrinsic response to either external physical triggers (e.g., photonic response or magnetic‐field response) or endogenous disease microenvironments (e.g., mild acidity or overexpressed hydrogen peroxide) and tissue‐regeneration bioactivity, these theragenerative biomaterials are extensively explored in various biomedical fields, including bone‐tumor therapy/regeneration, bone antibacterial therapy/regeneration, skin‐tumor therapy/regeneration, skin antibacterial therapy/regeneration, breast‐tumor therapy/adipose‐tissue regeneration, and osteoarticular‐tuberculosis therapy/bone‐tissue regeneration. The challenges faced and future developments of these distinctive theragenerative biomaterials are discussed, as are methods for further promoting their clinical translation.     

Marine-Derived Hydrogels for Biomedical Applications

Marine organisms provide novel and broad sources for the preparations and applications of biomaterials. Since the urgent requirement of bio-hydrogels to mimic tissue extracellular matrix (ECM), the natural biomacromolecule hydrogels derived from marine sources have received increasing attention. Benefiting from their outstanding bioactivity and biocompatibility, many attempts have been made to reconstruct ECM components by applying marine-derived natural hydrogels. Moreover, marine hydrogels have been successfully applied in biomedicine by means of microfluidics, electrospray, and bioprinting. In this review, the classification and characteristics of marine-derived hydrogels are summarized. In particular, their role in the development of biomaterials is also introduced. Then, the recent advances in bio-fabrication strategies for various hydrogel materials are focused upon. Besides, the influences of hydrogel types on their functions in biomedical applications are discussed in depth. Finally, critical reflections on the limitations and future development of marine-derived hydrogels are presented.     

Intelligent Sonocatalytic Nanoagents for Energy Conversion-Based Therapies

Sonodynamic therapy (SDT) utilizes ultrasound-irradiating sonosensitizers to convert ultrasonic vibrations into chemical energy and produce reactive oxygen species (ROS) that cause cell apoptosis or necrosis. SDT demonstrates significant potential in the treatment of deep tumors without normal tissue damage. Rapid advances in the efficacy of SDT have enabled the rational design and construction of novel intelligent sonocatalytic nanoagents (SCNs) with various functions for versatile biomedical applications. Herein, the most recent critical advancements in intelligent SCNs for energy conversion-based therapies are discussed. Typical SCNs including organic molecules, organic micro-/nanoparticles, inorganic micro-/nanoparticles, organic/inorganic hybrids, and piezoelectric materials are introduced and summarized in detail. Furthermore, these intelligent SCNs are designed for different energy conversion-based therapies such as SDT, SDT-assisted chemotherapy, SDT-assisted photodynamic therapy, SDT-assisted photothermal therapy, SDT-assisted gas therapy, SDT-assisted sonoporation from the cell membrane to the blood brain barrier, and high-intensity focused ultrasound-based sonothermal therapy. It is believed that this review will provide an overview of the application of intelligent SCNs in sonodynamic therapies to better understand the limitations and challenges of these SCNs and further promote their advancements for a broad range of biomedical applications.     

Spatiotemporally Controlled Photoresponsive Hydrogels: Design and Predictive Modeling from Processing through Application

Photoresponsive hydrogels (PRHs) are soft materials whose mechanical and chemical properties can be tuned spatially and temporally with relative ease. Both photo‐crosslinkable and photodegradable hydrogels find utility in a range of biomedical applications that require tissue‐like properties or programmable responses. Progress in engineering with PRHs is facilitated by the development of theoretical tools that enable optimization of their photochemistry, polymer matrices, nanofillers, and architecture. This review brings together models and design principles that enable key applications of PRHs in tissue engineering, drug delivery, and soft robotics, and highlights ongoing challenges in both modeling and application.     

Jellyfish‐Based Smart Wound Dressing Devices Containing In Situ Synthesized Antibacterial Nanoparticles

Although the negative consequences of the global phenomenon of jellyfish (JF) swarms are well recognized, the use of their biomass for practical applications is mostly limited to a niche in the Asian food industry. This fact is quite surprising since JF's biomass comprises useful biomaterials such as Q‐mucin glycoprotein and collagen. In this work, the JF biomass, collected from two different species, is used to prepare electrospun scaffolds composed of nanometric “core–shell”‐type fibers, in which adjustment of the electrospinning process parameters can easily control their mechanical, morphological, and chemical properties. This nonwoven scaffold shows excellent biocompatibility and biodegradability, indicating suitability for biomedical research contexts. Performed cell proliferation assays show that the scaffold could support the growth of cardiac cells, fitting the requirement of tissue engineering. Additional incorporation of in situ‐generated silver nanoparticles in these nanofibers produced mats with potent antibacterial properties. Preclinical trials with the resulted mats on porcine wound healing models exhibit fast and complete healing of wounds.     

Rational Design of Bioactive Hydrogels toward Periodontal Delivery: From Pathophysiology to Therapeutic Applications

Periodontitis is a biofilm-induced, host-mediated inflammatory disease that results in periodontal tissue destruction. The design of functional biomaterials based on disease pathophysiology is essential for enhancing their therapeutic effects in periodontitis treatment. As promising localized drug delivery systems and tissue engineering scaffolds, hydrogels have gained significant interest for controlled and sustained release of bioactive agents in periodontal applications. The rational design of bioactive hydrogels can facilitate bacterial control and modulate destructive host inflammation, thereby preventing the progression of periodontitis. In this review, the pathophysiological mechanisms underlying periodontitis as fundamental principles for the design of functional hydrogel systems are first introduced. In the following part, an overview is systematically provided of the types and functions of the bioactive hydrogel systems loaded with anti-bacterial and anti-inflammatory agents for periodontal delivery. Finally, the remaining challenges and future perspectives of hydrogel delivery systems for periodontal applications are proposed. It is believed that this review will inspire the rational design and development of innovative functional hydrogel biomaterials toward periodontal therapy.     

Rapid Construction of 3D Biomimetic Capillary Networks with Complex Morphology Using Dynamic Holographic Processing

Microvascular networks (MVNs) are crucial transportation systems in living creatures for nutrient distribution, fluid flow, energy transportation and so on. However, artificial manufacturing of MVNs, especially capillary networks with diameters (average 6 ≈ 9 µm), has always been a problem and bottleneck in tissue engineering due to the lack of efficient manufacturing methods. Herein, a dynamic holographic processing method is reported for producing 3D capillary networks with complex biomimetic morphologies. Combining the axial scanning of the focused beam and the dynamic display of holograms, biomimetic bifurcated microtubes, and porous microtubes with programmable morphologies are rapidly produced by two-photon polymerization (TPP). As a proof-of-concept demonstration, porous microtubes are used as 3D capillary network scaffolds for culturing human umbilical vein endothelial cells (HUVECs) to facilitate the exchange of nutrients and metabolites. Endothelial cells around the vascular scaffolds manifest obvious tight connections and 3D coverage after 3 days in vitro, which reveals that the scaffolds play a significant role in the morphology of dense vascularization. This flexible and rapid method of producing capillary networks provides a versatile platform for vascular physiology, tissue regeneration, and other biomedical areas.     

Polysaccharide–Peptide Conjugates: A Versatile Material Platform for Biomedical Applications

Natural polymers, such as polysaccharides and proteins, have been widely studied for numerous biomedical applications because of their bioactivity, natural origin, and biodegradability. To address the different needs of a broad spectrum of biomedical applications, natural polymers are modified with or conjugated to small molecular compounds, synthetic and natural polymers, and inorganic nanomaterials and surfaces. Among these hybrid materials, polysaccharide–peptide conjugates have drawn much attention due to their design flexibility, biocompatibility, tunable degradability, and structure similarity to naturally occurring glycoproteins. In the past 20 years, polysaccharide–peptide conjugates have demonstrated the promising potential to address many long-standing medical challenges. Thus, the design, conjugation chemistry and method, and biomedical applications of polysaccharide–peptide conjugates are summarized and discussed in this review. The conjugation techniques are reviewed from the view of the chemical reactions. Meanwhile, some inspiring examples of polysaccharide–peptide conjugates in biomedical applications, including drug delivery systems, nucleic acid delivery carriers, tissue engineering, and antimicrobial applications, are highlighted. Moreover, the outlook on the challenges and demands of polysaccharide–peptide conjugates is also elaborated.     

Light‐Guiding Biomaterials for Biomedical Applications

Optical techniques used in medical diagnosis, surgery, and therapy require efficient and flexible delivery of light from light sources to target tissues. While this need is currently fulfilled by glass and plastic optical fibers, recent emergence of biointegrated approaches, such as optogenetics and implanted devices, calls for novel waveguides with certain biophysical and biocompatible properties and desirable shapes beyond what the conventional optical fibers can offer. To this end, exploratory efforts have begun to harness various transparent biomaterials to develop waveguides that can serve existing applications better and enable new applications in future photomedicine. Here, the recent progress in this new area of research for developing biomaterial‐based optical waveguides is reviewed. It begins with a survey of biological light‐guiding structures found in plants and animals, a source of inspiration for biomaterial photonics engineering. The review then describes natural and synthetic polymers and hydrogels that offer appropriate optical properties, biocompatibility, biodegradability, and mechanical flexibility have been exploited for light‐guiding applications. Finally, perspectives on biomedical applications that may benefit from the unique properties and functionalities of light‐guiding biomaterials are discussed briefly.