Materials Horizons, Journal of Materials Chemistry B and Materials Advances Editor's Choice Web Collection: Recent Advances in Tissue Engineering Scaffolds

Tissue engineering has been developed as an advanced and attractive approach for treatment of various diseases and defects by combining the triad of cells, growth factors and scaffolds. Scaffolds serving as a temporary cell supporting template play an important role in controlling cell functions and guiding new tissue regeneration.¹ In recent years, many methods and techniques have been developed to control the compositions, structures and performances of porous scaffolds and hydrogels. This Editor's collection introduces some scaffold-related reviews and research articles that have been recently published in Materials Horizons, Journal of Materials Chemistry B and Materials Advances. Materials Horizons publishes work on innovative findings and breakthroughs in materials science. Journal of Materials Chemistry B emphasizes work on the properties and synthesis of materials with applications in biology and medicine, with a particular focus on advances in materials chemistry. Materials Advances publishes work on experimental and theoretical studies related to new understanding, applications, properties and synthesis of materials. This collection covers the preparation, composition and pore structure optimization, reinforcement and functionalization of porous scaffolds and hydrogels.

Biodegradable synthetic polymers such as poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL), natural polymers such as collagen, gelatin, chitosan and fibroin and bioceramics have been frequently used for tissue engineering scaffolds.² In addition to these biomaterials, polyphenol-based scaffolds have attracted increasing attention because of their adhesive, antioxidant, antimicrobial, photothermal and biocompatible properties. Polyphenols have been broadly investigated for surface modification and scaffold preparation. Li et al. summarized the structural and functional features, fabrication and tissue engineering applications of polyphenol-based scaffolds (https://doi.org/10.1039/d0mh01317j). Garskaite et al. reported composite scaffolds of carbonated hydroxyapatite, dipentaerythritol hexaacrylate, ethylene glycol dimethacrylate and gelatin (https://doi.org/10.1039/D0MA00498G). The composite scaffolds were prepared through polymerization and their hydrophilicity was improved.

Many preparation strategies have been reported for the design and optimization of scaffold composition and pore structures. As a useful technology, 3D printing can precisely control the structures of scaffolds to make site-specific implants.³ In a comprehensive review, the additive manufacturing of naturally derived polymers is summarized together with traditional preparation methods for bone tissue engineering applications (https://doi.org/10.1039/d0mh00277a). Photo-crosslinkable polymers are important for 3D printing. A facile method to synthesize photo-crosslinkable methacrylated chitosan using microwaves was reported (https://doi.org/10.1039/D1MA00765C). A high degree of methacrylation in the chitosan backbone was achieved rapidly under mild conditions. Losic et al. prepared a biocompatible ink composed of methylcellulose, kappa-carrageenan and conducting polymers (https://doi.org/10.1039/d0tb00627k). The bioink was used for easy 3D printing of scaffolds with high shape fidelity and good electrical conductivity. Malda et al. reported a visible light-induced crosslinking method using riboflavin as a photo-initiator in the presence of an electron acceptor to induce rapid gelation of cell-laden silk fibroin hydrogels (https://doi.org/10.1039/d0tb01731k). The hydrogels could encapsulate cells with a high viability and be used for 3D bioprinting.

Hydrogels have the advantages of similar biomimetic features to cellular microenvironments. Some functional hydrogels have been synthesized and applied for tissue engineering. Guan et al. synthesized gelatin–hydroxyphenyl hydrogels by dual-enzymatically cross-linking with horseradish peroxidase and galactose oxidase (https://doi.org/10.1039/d0tb02033h). The hydrogels enhanced neural differentiation of human umbilical cord mesenchymal stem cells and promoted nerve regeneration post-spinal cord injury. Lin et al. synthesized a tetraphenylethylene-based dipeptide and used it for the preparation of supramolecular hydrogels with tunable self-assembled nanostructures (https://doi.org/10.1039/d0tb01147a). The nanofiber and nanobelt structures in the hydrogels could be controlled by pH and showed different influences on cell adhesion and proliferation. A microfluidic platform was established for high-throughput preparation of cell-laden hydrogels with a gradient variation of biomaterials (https://doi.org/10.1039/d0mh00818d). The gradient structure hydrogels were used for cell/material screening and optimization of tissue engineering scaffolds.

Pore structures can affect cell loading, spatial distribution and functions in the scaffolds.⁴ Therefore, it is important to control the pore structures to maximize regeneration capacity. Pre-prepared ice particulates have been previously reported to control pore size, interconnectivity and micropatterning structures.⁵ In addition to the pre-prepared ice particulates, direct writing of fluid droplets onto cross-linkable fluid surfaces by inkjet printing was developed (https://doi.org/10.1039/d0mh01460e). The method was used to control pore geometry, porosity and patterning structures. Mesh-like collagen scaffolds were prepared using a synthetic polymer template (https://doi.org/10.1039/D1MA01166A). The collagen mesh promoted proliferation of human fibroblasts for dermal tissue engineering. Galluzzi et al. reported porous tubular nerve guide scaffolds of an amphiphilic alternating block polyurethane copolymer (https://doi.org/10.1039/d0tb02069a). The scaffolds induced fast formation of new blood vessels and showed a promotive effect on sciatic nerve regeneration.

A variety of methods have been reported for the preparation of porous hydrogels. However, generation of cell-sized pores in cell-laden hydrogels is challenging. Mongeau et al. developed a method called “triggered micropore-forming” bioprinting to prepare cell-laden hydrogel scaffolds with defined architecture and interconnected pores over a range of cell sizes (https://doi.org/10.1039/d0mh00813c). The structure, porosity and viscoelastic properties of the bioprinted hydrogels could be tuned. The method combined the merits of microphase separation, 3D embedding printing and viscoelastic hydrogels. Zhang et al. prepared polymer framework-reinforced hydrogel scaffolds with tunable internal microchannels (https://doi.org/10.1039/d0tb00616e). The hydrogel scaffolds showed enhanced mechanical strength and interconnected pore structures and promoted chondrogenesis.

Tissue engineering scaffolds need to have desirable mechanical properties to control cell functions, keep regeneration spaces and protect against suppression from surrounding tissues when implanted.⁶ Scaffold stiffness and elasticity should match the cells and tissues of interest to promote tissue regeneration because cells and tissues have their respective biomechanical properties. Hegmann et al. prepared scaffolds with tunable elasticity from a mixture of ε-caprolactone-D,L-lactide-based elastomers and cellulose nanocrystals (https://doi.org/10.1039/D0MA00676A). They disclosed how matching of scaffold mechanical properties to neuroblastoma cells and fibroblasts could affect cell behaviors. Crosslinked poly(glycerol sebacate)-based nanofibrous scaffolds with improved mechanical performance were prepared by electrospinning a blend solution with carrier molecules (https://doi.org/10.1039/d0ma00673d). The electrospun nanofibrous scaffolds were crosslinked by thermal treatment and the carrier molecules were removed after curing. Composite alginate hydrogels were prepared by incorporation of poly(vinyl alcohol-co-ethylene) nanofibers in a hydrogel matrix (https://doi.org/10.1039/d0tb01948h). The composite hydrogels were reinforced by the nanofibers and showed improved mechanical properties. The composite hydrogels also showed inhibitory effects on bacteria, while supporting cell adhesion and proliferation. Pei et al. prepared an injectable double network hydrogel of collagen, poly(ethylene glycol) and silk fibroin and used it for loading of bone marrow mesenchymal stem cells (https://doi.org/10.1039/D1MA00285F). The hydrogel showed improved mechanical properties and promoted cartilage regeneration. Heise et al. reported polypeptide-based interpenetrating network (IPN) hydrogels (https://doi.org/10.1039/d0tb01422b). The IPN hydrogels exhibited enhanced mechanical properties and good biocompatibility.

Advanced scaffolds with multi-functions have been designed and fabricated for maximized therapeutic effects. Hybridization of polymer biomaterials and bioceramics with functional nanomaterials, bioactive factors, therapeutic drugs and antibiotics has been carried out to render composite scaffolds with multi-functions. In a review, Paul et al. summarized the latest advances of multi-functional scaffolds for chronic would healing applications (https://doi.org/10.1039/d2mh00115b). The bioadhesive, antimicrobial, proangiogenic and anti-inflammatory properties of the scaffolds were highlighted. Han et al. hybridized graphene oxide nanoparticles with poly(L-lactide-co-ε-caprolactone) and laminin by electrospinning (https://doi.org/10.1039/D0MA00733A). The nanofibrous composite scaffolds promoted neurite outgrowth and alignment of mouse hippocampal neuronal cells. Guan et al. prepared composite scaffolds of magnetic lanthanum-doped hydroxyapatite and chitosan for recruitment of stem cells and modulation of host immune responses after implantation (https://doi.org/10.1039/d0tb00342e). The composite scaffold promoted the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells and new bone regeneration. Zhang et al. hybridized reduced graphene oxide with gelatin methacryloyl and PCL via electrospinning to prepare nanofibrous composite scaffolds with enhanced electrical conductivity (https://doi.org/10.1039/d0tb00779j). Nerve guidance conduits of the nanofibrous composites in the absence of electrical stimulation promoted sensory/motor nerve regeneration and functional recovery in rats. Cao et al. prepared composite hydrogels of gelatin methacrylamide, poly(ethylene glycol)-tetrathiol and MgO nanoparticles with a porous structure by a mild and fast thiol–ene click reaction (https://doi.org/10.1039/d0tb00901f). The composite hydrogels could release magnesium ions and promote bone regeneration. Thomas et al. reported silver nanoparticle-functionalized PCL composite scaffolds (https://doi.org/10.1039/D1MA00444A). The antibacterial properties of the composite scaffolds were improved. Antibiotic clindamycin-loaded PLA nanoparticles were incorporated in fibrin hydrogels to prepare composite hydrogels with antibacterial properties for dental pulp tissue regeneration (https://doi.org/10.1039/d0tb00989j). The composite hydrogels had good antibacterial and antibiofilm properties without any influence on cell viability and functions.

Bioactive factors and components have been incorporated in composite scaffolds for enhanced regenerative functionality. Scaffolds with an angiogenesis-promoting capacity were prepared by functionalization of 3D printed scaffolds of mesoporous calcium silicate with an osteopontin sequenced polypeptide (https://doi.org/10.1039/d0tb00527d). The composite scaffolds promoted angiogenesis and new bone growth after implantation. Shakir et al. prepared nanocomposite scaffolds of nano-hydroxyapatite, carboxymethyl chitosan, β-cyclodextrin and date palm seed extract by a co-precipitation method (https://doi.org/10.1039/D1MA00286D). The nanocomposite scaffolds showed high bioactivity and promoted the regeneration of rat cranial bone. Chen et al. reported composite scaffolds of Sr-doped bioactive glass (SrBG), PLGA and interferon γ for modulation of inflammation (https://doi.org/10.1039/d0tb02333g). The composite scaffolds stimulated a stepwise polarization of macrophages and showed a promotive effect on bone regeneration.

This collection only lists some of the many recent articles published in Materials Horizons, Journal of Materials Chemistry B and Materials Advances on the topic of tissue engineering scaffolds. I hope the collection can help our readers to catch up on the latest information on the topic.

References

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2. M. S. Shoichet, Macromolecules, 2010, 43, 581–591.
3. R. Levato, T. Jungst, R. G. Scheuring, T. Blunk, J. Groll and J. Malda, Adv. Mater., 2020, 32, 1906423.
4. Q. L. Loh and C. Choong, Tissue Eng., Part B, 2013, 19, 485–502.
5. H. H. Oh, Y. G. Ko, H. Lu, N. Kawazoe and G. Chen, Adv. Mater., 2012, 24, 4311–4316.
6. F. T. Moutos, L. E. Freed and F. Guilak, Nat. Mater., 2007, 6, 162–167.

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