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Soft matter is an inter- and multidisciplinary research field that focuses on the design and development of innovative soft materials and molecular assemblies, provides fundamental insights on their behaviour and characterization, and addresses different applications across a wide array of disciplines at the interface between chemistry, biochemistry, physics, materials science and engineering, chemical engineering, nanoscience, nanotechnology, nanomedicine, biomedical engineering, and biology. Examples of soft materials include polymers, colloids, surfactants, liquid crystals, (hydro)gels, foams, emulsions, and a wide variety of biological materials. In fact, the soft matter research field has a broad international audience and has been the subject of considerable interest over the past decades owing to its key importance in biomedical and non-biomedical applications. In particular, the molecular design, synthesis, development, processing, and advanced characterization of biomimetic and bioinspired soft materials and complex systems, denoting emerging properties and multifunctionalities, have gathered growing interest in the biomedical arena over the past decades owing to their intrinsic ability to recreate the structure, dynamics, and functional features of biological systems. For instance, soft materials can be rationally designed to disclose unique features, including (multi)responsiveness, self-assembly and self-healing capacity, bioinstructive and adaptive behaviour, dynamic features, multi-scale organization, enhanced structural properties, among others.

This book, encompassing 28 chapters, covers many aspects of soft matter in the biomedical context and is organized into four main sections, providing the readers with a comprehensive overview of the fundamental concepts, sources, and properties of soft matter (Chapters 1–8), bioinspired materials and surfaces (Chapters 9–13), soft nanobiomaterials (Chapters 14–18), and biomedical applications of soft biomaterials (Chapters 19–28). Protein- (Chapters 1–5) and polysaccharide-based (Chapters 6–8) soft matter for biomedical applications are the focus of the first 8 chapters. Chapters 1–5 provide details of research on mutable collagenous tissue of echinoderms (Chapter 1) and how it can be used as a source of inspiration to design new artificial biomimetic materials, as well as the combination of synchrotron small-angle X-ray scattering with multiscale mechanical modelling for elucidating the structure of biological materials important for the development of new soft biomaterials (Chapter 2). An overview on biomimetic collagen-containing (Chapter 3) and silk fibroin-based (Chapter 4) soft biomaterials for tissue engineering, as well as on the design, synthesis, and properties of poly(ethylene glycol)-based synthetic molecules for protein aggregation suppression and folding promotion (Chapter 5) are provided. Chapters 6–8 give an in-depth overview of the physicochemical, structural, and biological properties of either microbial- (Chapter 6) or marine-based (Chapters 7 and 8) polysaccharides and their chemical derivatives, by applying a wide variety of chemical methodologies, in developing advanced multifunctional biomaterials for addressing a wide array of biomedical applications. Chapters 9–13 focus on bioinspired materials and surfaces. Chapters 9 and 10 spotlight peptides, in particular genetically engineered (Chapter 9) and short peptides (Chapter 10) as attractive molecular building blocks for the rational design, synthesis, and development of self-assembling driven tunable peptide-based soft biomaterials with emergent properties and functions for biomedicine. Chapters 11, 12 and 13 denote well-defined surface functionalization strategies to create either biomimetic or bioinspired soft biomaterial surfaces. Chapter 11 highlights the role of polymer brushes, i.e., polymeric coatings tethered to solid surfaces by one end as a method to precisely engineer biomaterials tailored to specific biomedical applications, including for the regulation of cell behaviour and controlled release of drugs/therapeutics. Chapter 12 showcases how the chemistry, topography, and stiffness of bioinstructive biomaterial surfaces can trigger the self-assembly of proteins and regulate mesenchymal stem cell fate to understand fundamental mechanisms at the cell/material interface. Chapter 13 introduces the layer-by-layer (LbL) assembly technology as a highly versatile bottom-up approach to coat and functionalize surfaces with functional biomaterials, such as polysaccharides and proteins, in a precisely controlled fashion aiming to recreate the extracellular matrix (ECM), control cell functions, and understand the native cellular microenvironment, including cell–ECM interactions. Subsequent chapters describe the development of soft nanobiomaterials addressing a plethora of biomedical applications. Chapter 14 gives an overview of hybrid mesoporous core–shell silica–polymer nanoparticles as smart and versatile nanocarriers for on-demand controlled release of large cargo payloads in theranostics. Chapter 15 details the preparation of nanoliposomes and nanoliposome-hydrogel scaffolds for controlled drug delivery and tissue engineering. Chapter 16 reviews the applicability of cyclodextrins for the encapsulation, protection, and sustained drug release in producing advanced drug delivery systems and tissue engineered scaffolds via emergent processing technologies, including 3D printing, electrospinning, microfluidics, microneedles, and metal–organic frameworks. Chapter 17 shifts the focus to the build-up of ECM-inspired complex soft nanofibrillar biomaterials by combining fiber spinning routes with additive manufacturing for soft human tissue regeneration, including heart, skin, vascular grafts, and peripheral nerves. Chapter 18 revisits the simplicity and high versatility of the LbL assembly technology in coating a myriad of inanimate and animate templates, spanning from 0D to 3D, with a multitude of complementary materials for shaping a wide array of soft-based LbL architectures for biomedicine. The final chapters of the book cover the applications of soft biomaterials in either controlled drug/therapeutics delivery (Chapters 19–22) and as 3D cell culture and medical devices (Chapters 23–28). Chapter 19 discusses the development of stimuli-responsive nanobiomaterials in the form of hydrogels for the spatiotemporal delivery of therapeutics at targeted sites. Chapter 20 puts liposomes in the limelight as enhanced stimuli-sensitive systems for the encapsulation and targeted release of both hydrophobic and hydrophilic drugs, which is transversal to a multitude of biomedical applications. Then, the molecular design, synthesis, development, and role of polysaccharide-based and stimuli-responsive hydrogels as smart reservoirs for on-demand site-specific controlled and sustained release of drugs/therapeutics are discussed in Chapters 21 and 22, respectively. The development of soft systems and cell-based soft biomaterials is discussed in the last six chapters. Chapter 23 discloses hybrid stimuli-sensitive nanocomposite hydrogels containing soft nanoparticles suitable for tissue engineering and regenerative medicine strategies while Chapter 24 highlights 3D-printed soft hydrogels for cell encapsulation. Then, Chapters 25 and 26 focus on the design and development of decellularized ECM (Chapter 25) and human protein-based soft biomaterials (Chapter 26) for in vitro disease modelling and soft tissue regeneration, respectively. The last two chapters shift the focus to two recently emerging fields of research, namely soft material robotics (Chapter 27) and scaffold-free biomimetic soft biomaterials (Chapter 28), disclosing the fabrication of soft robots as more compliant tools for minimally invasive surgery and cell-based soft biomaterials to assemble complex and orchestrate functions of soft tissues.

We believe this is a much needed and timely book in the field of soft matter for biomedicine that will hopefully be useful and inspire the community working in the field.

Assembling this book was only possible thanks to the insightful and generous contributions of many of our colleagues working on diverse areas related to soft biomaterials. Hence, we would like to express our sincere appreciation to all authors who have kindly contributed their chapters. We are immensely grateful to have them sharing their up-to-date knowledge and expertise, providing authoritative and critical contributions, and investing their valuable time under such unprecedented times to make this book possible. We would also like to very much thank the Royal Society of Chemistry (RSC) for the opportunity to work on this book. Special thanks go to the editorial and production staff at the RSC, in particular to Michelle Carey, Connor Sheppard, and Lewis Pearce for all their kind support and professional editorial assistance throughout the commissioning and production process in putting this book together and bringing it into reality.

Helena S. Azevedo, João F. Mano and João Borges

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