Biomaterials for Regenerative Medicine
Authors: Shengmin Zhang, Antonios G. Mikos
Journal: Advanced Healthcare Materials (2020)

Recent advances in biofabrication and biomaterials science have enabled more accurate recapitulation of complex tissue microenvironments, and modern tissue engineering approaches expand upon the traditional paradigm by incorporating multiple materials over a range of architectural scales and by integrating biochemical and physical components that influence cellular behavior. This special issue highlights a breadth of strategies used to promote the regeneration of functional bone, cartilage, muscle, and skin and provides an overview of the diverse research that is driving the field forward. One notable strategy for bone tissue repair is the use of modified Ti or Ti-alloy implants. To increase the osteogenic capabilities of these materials and reduce the risk of infection, bifunctional elements can be added to micro- or nano-structured surface oxide coatings to alter surface physicochemical properties. A review outlining this progress in this field is included in this issue by Kaifu Huo et al. (2000681). Another interesting tactic for bone tissue repair is designing biomaterials that interact with the fracture hematoma formed upon injury to bone tissue. The effects of biomaterials on blood coagulation and hematoma characteristics are examined in a review article by Yin Xiao et al. (2000726), and perspectives on enhancing osteogenesis by regulating hematoma properties are provided. Similarly, neovascularization of de novo bone tissue is critical for tissue ingrowth and repair. An original article by Shengmin Zhang et al. highlights the leverage of a selective laser sintering technique to produce a porous polycaprolactone/hydroxyapatite scaffold that enhances blood vessel formation and bone regeneration when VEGF is immobilized on the scaffold surface (2000727). More recently, three-dimensional printing (3DP) and additive manufacturing (AM) have emerged as promising strategies in the field. To further advance bone tissue engineering, an original research article by Yinghong Zhou et al. leveraged bone particles to create a printable, biofunctionalized GelMA-based bioink. At variable compositions, bioprinted constructs with cell-laden bone particles of varying size enabled cell colonization of the scaffold and the expression of early osteogenic markers (2001323). This special issue offers multiple reviews on the potential of 3DP in tissue engineering as well. The applications of various materials and techniques in producing complex bone tissue engineering scaffolds via AM are discussed by Jie Liu et al., as well as preclinical studies, clinical applications and future prospects for these materials (2000724). A review highlighting the advantageous nature of 3DP for mimicking the complex composition and hierarchical structure of native tissue via multimaterial and multiscale fabrication is also presented in this issue by Chengtie Wu et al. (2000208). In this article, traditional bioinspired biomaterials designs are discussed, as well as biological composition and structure inspired designs. The utility of 3DP also extends to repairing osteochondral defects. An original research article by Xuetao Shi et al. leverages a biomimetic biphasic scaffold with a hyaluronic acid hydrogel layer to mimic cartilage tissue and a 3DP hydroxyapatite layer to mimic bone tissue to facilitate the layer-specific release of kartogenin and alendronate, respectively. In addition to the semi-immersion-bound biphasic layers, the scaffold induced mesenchymal stem cells to differentiate to both chondrocytes and osteoblasts in a layer-specific manner (2000076). This issue also considers the applications of 3DP in osteochondral tissue engineering through a review by Liangbin Zhou et al. examining various approaches to repairing osteochondral defects, such as scaffold and scaffold-free strategies, various scaffold architectures, the spatiotemporal release of bioactive factors and drugs, and the delivery of progenitor and tissue-specific cells (2001008). Clinical applications of existing tissue engineering strategies and emerging bioprinting technologies are also considered. In addition to bone and cartilage tissue engineering, this issue extends to both cardiac and skeletal muscle tissue repair. As cardiovascular diseases are a leading cause of death worldwide, the regeneration of injured cardiac muscle has great clinical applications. A review by Lin Wang et al. examines the potential of silk biomaterials and composites as cardiac patches and hydrogels and as delivery vehicles for bioactive species (2000735). Because existing skeletal muscle repair strategies do not adequately restore tissue structure or function, scaffolds that mediate external stimulation to engineered skeletal muscle tissue have great clinical potential as they more effectively mimic physical microenvironments. The incorporation of nanomaterial additives that respond to electrical, magnetic, and photothermal stimulation into skeletal muscle tissue engineering constructs and the myogenic potential of these biomaterials is also reviewed by Antonios G. Mikos et al. (2000730). This special issue extends beyond musculoskeletal tissue engineering to include skin reconstruction. An original article by Jianglin Wang et al. reports the development of a nanofibrous chitin and silk fibroin wound dressing that possesses good tensile strength and antibiotic activity. This dressing also promoted the vasculature formation and the regeneration of hair follicles, skin components that have previously been difficult to engineer (2000035). Finally, this issue provides insights into various strategies used in the field to influence cellular behavior. For instance, extracellular matrix-derived ligands can be employed to illicit certain cellular responses based on integrin interactions. This issue features a review by Elizabeth Cosgriff-Hernandez and co-workers outlining the integrin-mediated processes observed in angiogenesis, wound healing and bone regeneration and discusses biomaterials with integrin-targeting motifs that both enhance tissue regeneration and enable probing of cellular processes (2000795). Like biochemical functionalities, extracellular matrix mechanical properties can also influence cellular behavior. The effects of the viscosity of a biphasic gelatin solution/hydrogel system on human bone marrow-derived mesenchymal stem cell differentiation have been investigated, in contrast to previously studied elasticity and viscoelasticity parameters. This study by Guoping Chen et al. found that high viscosity matrices favored osteogenic differentiation while low viscosity matrices promoted adipogenic differentiation (2000617). The final review presented here, by Heungsoo Shin and co-workers, highlights the broad applicability of 3D composite spheroid systems in accelerating spheroid formation, improving spheroid viability and mechanical properties, and in directing stem cell fate (2000608). This article also provides an overview of the applications of spheroid technologies in reconstructing artificial tissue. This special issue demonstrates the recent progress made in bone, cartilage, muscle and skin tissue engineering through emerging technologies such as 3DP and AM, the use of multimaterial and multiscale tissue engineering constructs, and through strategies that more effectively mimic biochemical and physical microenvironments observed in native tissue. The wide breadth of the material covered in this special issue reflects the diverse strategies employed in the field, and represents several avenues towards clinically impactful therapeutics. The authors would like to acknowledge support from the National Natural Science Foundation of China (31870960) and National Institutes of Health (P41 EB023833). Shengmin Zhang is the University Chair Professor of biomedical engineering, biomaterials and regenerative medicine at Huazhong University of Science and Technology. His interests focus on regenerative medical materials and devices, bioprinting and biomanufacturing, and regulatory science for medical devices. Currently, he is the director of the Advanced Biomaterials and Tissue Engineering Center, and the Director of Institute of Regulatory Science for Medical Devices at Huazhong University of Science and Technology. Antonios G. Mikos is the Louis Calder Professor of bioengineering and chemical and biomolecular engineering at Rice University. His research focuses on the synthesis, processing, and evaluation of new biomaterials for use as scaffolds for tissue engineering, as carriers for controlled drug delivery, as non-viral vectors for gene therapy, and as platforms for disease modeling.