For complex tissue grafts that require stratified structural and mechanical properties, a new generation of biomaterials is helping to reconstruct the anisotropy, nonlinearity and local mechanical properties of the native tissue. One emerging strategy for forming tailored composite scaffolds is to reinforce the hydrogels with encapsulated cells using textile-engineered fiber structures. Fibers can be spun, extruded or electrospun, offering a range of fiber diameters, mechanical features and fiber orientations to meet the tissue-specific needs. The fibers can be combined, wound, braided, woven or twisted to design structures with the desired transport properties, anisotropy and biomechanics. After this step, the fiber system can be embedded within a hydrogel or further modified by cross-linking to alter the mechanical properties, adjust degradation or enhance handling. These scaffolds were inspired by the architectures of native tissues. Examples include fiber composites for the reconstruction of ligaments, cartilage [32
] and intervertebral discs [33
Figure 3 Scaffold design: composite biomaterials for complex grafts. (a) Composite scaffold for cartilage tissue engineering made by microscale weaving of polycaprolactone fibers. Top: a schematic of the weave; bottom left: surface view of the weave by scanning (more ...)
For bone, mechanically stiff biomaterials with options for medium perfusion and vascularization are required to support cell expansion, as well as the production of bone matrix rich in type I collagen and hydroxyapatite. The structural stability of bone scaffolds and scaffold mineralization are important to avoid premature collapse of the open porous structure and to maintain nutrient transport into the growing bone tissue [34
]. Matrix-mediated or exogenous delivery of signaling molecules, such as bone morphogenetic protein-2 (BMP-2), are also important. Porous degradable polymers, including polylactic-co-glycolic acid (PLGA), collagen, polycaprolactone (PCL) and silk fibroin, are among several materials being studied that could meet these requirements.
By contrast, native cartilage matrix consists of a highly hydrated proteoglycan hydrogel embedded into a type II collagen network. It has been known for more than two decades that hydrogels support the spherical shape and normal phenotype of chondrocytes [35
]. Based on these early findings, many studies have used hydrogels, such as agarose, alginate, chitosan and photopolymerizing systems, to engineer cartilage tissue [4
]. In a study of human chondrocytes in six different scaffolds, the highest matrix production was recorded in collagen gel [38
]. Notably, hydrogel systems yielded constructs with the highest compressive moduli among all scaffolds used: in fact, the moduli were similar to those for native articular cartilage [8
Silk protein biomaterials are among those actively pursued for osteochondral tissue engineering [39
]. Silk protein fibers are the strongest and toughest natural fibers known, providing an excellent starting point for use as scaffolds. Silk processing and self-assembly enable the formation of a range of silk-based scaffolds, including hydrogels, films, conformal coatings, porous matrices, nanoscale fibers and large fibers [40
]. Importantly, the crystallinity (β sheet content) of silk can be controlled by the mode of processing, thereby providing an ability to modulate mechanical properties and degradation [42
]. The presence of diverse amino acid side chains facilitates attachment of growth factors that are necessary for topological control of cell differentiation [45
]. Controlled mineralization can also be achieved to generate highly porous and stiff matrices suitable for tissue engineering of bone [46
]. Together, these features enable the design of silk-based scaffolds in the form of hydrogel for cartilage formation (), porous mineralized scaffold for bone formation () and composite scaffolds for engineering stratified osteochondral tissues.
For any designed scaffold system, integration between the cartilaginous and osseous parts and integration with native tissue are critical [39
]. Integration can be approached via suturing, by cell-mediated ECM formation and by the use of fibrin and other glues. The biomaterial degradation also needs to be tailored to match the rate of tissue formation so that the development of new tissue is balanced with the degradation of the scaffold; this issue has not been explored in depth to date.