Hydrogels, due to their excellent biochemical and mechnical property, have shown attractive advantages in the field of wound dressings. However, a comprehensive review of the functional hydrogel as a wound dressing is still lacking. This work first summarizes the skin wound healing process and relates evaluation parameters and then reviews the advanced functions of hydrogel dressings such as antimicrobial property, adhesion and hemostasis, anti-inflammatory and anti-oxidation, substance delivery, self-healing, stimulus response, conductivity, and the recently emerged wound monitoring feature, and the strategies adopted to achieve these functions are all classified and discussed. Furthermore, applications of hydrogel wound dressing for the treatment of different types of wounds such as incisional wound and the excisional wound are summarized. Chronic wounds are also mentioned, and the focus of attention on infected wounds, burn wounds, and diabetic wounds is discussed. Finally, the future directions of hydrogel wound dressings for wound healing are further proposed.

Functional Hydrogels as Wound Dressing to Enhance Wound Healing.

Successful materials design for bone-tissue engineering requires an understanding of the composition and structure of native bone tissue, as well as appropriate selection of biomimetic natural or tunable synthetic materials (biomaterials), such as polymers, bioceramics, metals and composites. Scalable fabrication technologies that enable control over construct architecture at multiple length scales, including three-dimensional printing and electric-field-assisted techniques, can then be employed to process these biomaterials into suitable forms for bone-tissue engineering. In this Review, we provide an overview of materials-design considerations for bone-tissue-engineering applications in both disease modelling and treatment of injuries and disease in humans. We outline the materials-design pathway from implementation strategy through selection of materials and fabrication methods to evaluation. Finally, we discuss unmet needs and current challenges in the development of ideal materials for bone-tissue regeneration and highlight emerging strategies in the field. Design of bone-tissue-engineering materials involves consideration of multiple, often conflicting, requirements. This Review discusses these considerations and highlights scalable technologies that can fabricate natural and synthetic biomaterials (polymers, bioceramics, metals and composites) into forms suitable for bone-tissue-engineering applications in human therapies and disease models.

Materials design for bone-tissue engineering

3D printing alias additive manufacturing can transform 3D virtual models created by computer-aided design (CAD) into physical 3D objects in a layer-by-layer manner dispensing with conventional molding or machining. Since the incipiency, significant advancements have been achieved in understanding the process of 3D printing and the relationship of component, structure, property and application of the created objects. Because hydrogels are one of the most feasible classes of ink materials for 3D printing and this field has been rapidly advancing, this Review focuses on hydrogel designs and development of advanced hydrogel-based biomaterial inks and bioinks for 3D printing. It covers 3D printing techniques including laser printing (stereolithography, two-photon polymerization), extrusion printing (3D plotting, direct ink writing), inkjet printing, 3D bioprinting, 4D printing and 4D bioprinting. It provides a comprehensive overview and discussion of the tailorability of material, mechanical, physical, chemical and biological properties of hydrogels to enable advanced hydrogel designs for 3D printing. The range of hydrogel-forming polymers covered encompasses biopolymers, synthetic polymers, polymer blends, nanocomposites, functional polymers, and cell-laden systems. The representative biomedical applications selected demonstrate how hydrogel-based 3D printing is being exploited in tissue engineering, regenerative medicine, cancer research, in vitro disease modeling, high-throughput drug screening, surgical preparation, soft robotics and flexible wearable electronics. Incomparable by thermoplastics, thermosets, ceramics and metals, hydrogel-based 3D printing is playing a pivotal role in the design and creation of advanced functional (bio)systems in a customizable way. An outlook on future directions of hydrogel-based 3D printing is presented.

3D printing of hydrogels: Rational design strategies and emerging biomedical applications

The design and development of a smart bioadhesive hydrogel sealant with self-healing and excellent antibacterial activity to achieve high wound closure effectiveness and post-wound-closure care is highly desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial self-healing hydrogels with promising traits were designed through dual-dynamic-bond cross-linking among ferric iron (Fe), protocatechualdehyde (PA) containing catechol and aldehyde groups and quaternized chitosan (QCS) to enable the closure of skin incisions and promotion of methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. The dual-dynamic-bond cross-linking of a pH-sensitive coordinate bond (catechol-Fe) and dynamic Schiff base bonds with reversible breakage and re-formation equips the hydrogel with excellent autonomous healing and on-demand dissolution or removal properties. Additionally, the hydrogel presents injectability, good biocompatibility and antibacterial activity, multifunctional adhesiveness, and hemostasis as well as NIR responsiveness. The in vivo evaluation in a rat skin incision model and infected full-thickness skin wound model revealed the high wound closure effectiveness and post-wound-closure care of the smart hydrogels, demonstrating its great potential in dealing with skin incisions and infected full-thickness skin wounds.

Dual-Dynamic-Bond Cross-Linked Antibacterial Adhesive Hydrogel Sealants with On-Demand Removability for Post-Wound-Closure and Infected Wound Healing.

Conducting polymer hydrogels (CPHs) have emerged as a fascinating class of smart soft matters important for various advanced applications. However, achieving the synergistic characteristics of cond...

Nanocellulose-Mediated Electroconductive Self-Healing Hydrogels with High Strength, Plasticity, Viscoelasticity, Stretchability, and Biocompatibility toward Multifunctional Applications.

Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

Biomacromolecules with poor mechanical properties cannot satisfy the stringent requirement for load-bearing as bioscaffolds. Herein, a biodegradable high-strength supramolecular polymer strengthened hydrogel composed of cleavable poly(N-acryloyl 2-glycine) (PACG) and methacrylated gelatin (GelMA) (PACG-GelMA) is successfully constructed by photo-initiated polymerization. Introducing hydrogen bond-strengthened PACG contributes to a significant increase in the mechanical strengths of gelatin hydrogel with a high tensile strength (up to 1.1 MPa), outstanding compressive strength (up to 12.4 MPa), large Young's modulus (up to 320 kPa), and high compression modulus (up to 837 kPa). In turn, the GelMA chemical crosslinking could stabilize the temporary PACG network, showing tunable biodegradability by adjusting ACG/GelMA ratios. Further, a biohybrid gradient scaffold consisting of top layer of PACG-GelMA hydrogel-Mn2+ and bottom layer of PACG-GelMA hydrogel-bioactive glass is fabricated for repair of osteochondral defects by a 3D printing technique. In vitro biological experiments demonstrate that the biohybrid gradient hydrogel scaffold not only supports cell attachment and spreading but also enhances gene expression of chondrogenic-related and osteogenic-related differentiation of human bone marrow stem cells. Around 12 weeks after in vivo implantation, the biohybrid gradient hydrogel scaffold significantly facilitates concurrent regeneration of cartilage and subchondral bone in a rat model.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/advs.201900867

Osteochondral Regeneration with 3D-Printed Biodegradable High-Strength Supramolecular Polymer Reinforced-Gelatin Hydrogel Scaffolds.

The emerging 3D bioprinting technique that is strongly dependent on the development of bioinks offers a promising opportunity to customize personalized bioscaffolds for precision and individualized therapy of bone defects Hydrogels are one sort of attractive scaffolding materials due to their resemblance to extracellular matrices Although much progress has been made in designing and fabricating high strength hydrogels, very few of them have been extended to the treatment of bone defects In this work, we developed a hybrid bioink composed of a hydrogen bonding monomer (N-acryloyl glycinamide) (NAGA) and nanoclay The hybrid ink could be conveniently tailored as a high strength PNAGA-Clay composite scaffold under UV light illumination of printed prehydrogel The hydrogen bonding combined with physical cross-linking of nanoclay contributed to the superior mechanical performances as well as swelling stability of the hydrogels and bioscaffols The sustainable release of intrinsic Mg2+ and Si4+ from the PNAG

3D-Printed High Strength Bioactive Supramolecular Polymer/Clay Nanocomposite Hydrogel Scaffold for Bone Regeneration

An Injectable Supramolecular Polymer Nanocomposite Hydrogel for Prevention of Breast Cancer Recurrence with Theranostic and Mammoplastic Functions

Over the past decade, high strength hydrogels have been intensively investigated. However, developing high strength biofunctional hydrogels for eliciting bone regeneration has been rarely reported. In this work, a mineralized high strength and tough hydrogel is synthesized by one-step copolymerization of acrylonitrile, 1-vinylimidazole, and polyethylene glycol diacrylate, followed by in situ precipitation mineralization. It is demonstrated that the CNCN dipole–dipole pairings combined with the interaction of CaP nanocrystals with polymer chains contribute to tremendous increase of tensile/compressive strength, modulus, and fracture energy up to 6.1 MPa, 11.5 MPa, 6.47 MPa, and 7935 J m−2, respectively. The biomineralization is shown to facilitate the attachment and proliferation of C2C12 cells in vitro. This biomineralized hydrogel scaffold is implanted into an 8 mm diameter critical-size of calvarial defect of rats to evaluate the bone regeneration. 12 week postsurgery results reveal that the mineralized hydrogel exhibits the highest bone volume and density within the defect as measured by computed tomography and histology. This mineralized high strength and tough hydrogel offers a broad range of possibilities to be developed as biofunctional scaffold to promote the reconstruction and regeneration of not only bone, but also load-bearing connective tissue.

Fei Gao

Papers

Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

Osteochondral Regeneration with 3D-Printed Biodegradable High-Strength Supramolecular Polymer Reinforced-Gelatin Hydrogel Scaffolds.

3D-Printed High Strength Bioactive Supramolecular Polymer/Clay Nanocomposite Hydrogel Scaffold for Bone Regeneration

An Injectable Supramolecular Polymer Nanocomposite Hydrogel for Prevention of Breast Cancer Recurrence with Theranostic and Mammoplastic Functions

A Mineralized High Strength and Tough Hydrogel for Skull Bone Regeneration