In contrast to large lot variation, low mechanical strength and uncontrollable degradation of natural materials (e.g., collagen, chondroitin and hyaluronic acid) 14, 15, 16, synthetic polymers offer better control of the physicochemical properties and processability. Significant progresses have been made to fabricate scaffolds for tissue regeneration using synthetic or natural materials 12, 13. Furthermore, in vivo recruitment of tissue-forming cells into scaffolds is closely regulated by their physicochemical properties, e.g., pore size, porosity, bioactivities, stiffness, etc 10, 11. Thus, scaffold-guided cell arrangement is a vital factor towards functional regeneration and maturation of oriented tissues 8, 9. Such an organisation modulates the mechanical properties of tissues, and impacts upon cellular functions, such as cytoskeleton reorganisation, integrin activation, gene expression and ECM remodelling 7, 8. For example, in oriented tissues (e.g., muscle, nerve, artery), obvious alignment of cells and ECM are observed 7, 8. To achieve the unique physiological functions, many tissues in our body are anisotropic with distinct spatial organisation of their extracellular matrix (ECM) and residing cells. Accumulative evidence showed that well-designed scaffolds indeed induce the formation of functional neo-tissue, in vivo, by harnessing endogenous regenerative capacity 4, 5, 6. In view of the high risk of donor site morbidity from autografting and the limited donor tissues and organs for allotransplantation 1, emerging attention has shifted to engineer biomaterials that can trigger the body’s innate regenerative mechanism to restore, maintain, or improve the damaged tissue 2, 3. Trauma, disease and congenital abnormalities often lead to tissue dysfunction or organ loss, requiring prompt restoration of the lost functions. This strategy has potential to yield inducible biomaterials with applications across tissue engineering and regenerative medicine. We demonstrate the versatility and flexibility of these scaffolds by regenerating vascularized and innervated neo-muscle, vascularized neo-nerve and pulsatile neo-artery with functional integration. The advantages of such ECM-C scaffolds are evidenced by close regulation of in vitro cell activities, and enhanced cell infiltration and vascularization upon in vivo implantation. Here, we engineer ECM scaffolds with parallel microchannels (ECM-C) by subcutaneous implantation of sacrificial templates, followed by template removal and decellularization. However, the lack of hierarchical porous structure fails to provide cells with guidance cues for directional migration and spatial organization, and consequently limit the morpho-functional integration for oriented tissues. Extracellular matrix (ECM) scaffolds derived from cultured cells or natural tissues exhibit superior biocompatibility and trigger favourable immune responses. Here we review the current state and clinical validation of these next-generation therapeutics.Īdnectin Affibody Anticalin DARPin antibody immunoglobulin.Implanted scaffolds with inductive niches can facilitate the recruitment and differentiation of host cells, thereby enhancing endogenous tissue regeneration. This includes the abovementioned pioneering examples as well as designed ankyrin repeat proteins (DARPins). However, despite strong interest from basic science, only a handful of those protein scaffolds have undergone biopharmaceutical development up to the clinical stage.
In fact, engineered protein scaffolds with useful binding specificities, mostly directed against targets of biomedical relevance, constitute an area of active research today, which has yielded versatile reagents as laboratory tools. Since then, this concept has expanded considerably, including many other protein templates. Early examples were the Affibody, Monobody (Adnectin), and Anticalin proteins, which were derived from fragments of streptococcal protein A, from the tenth type III domain of human fibronectin, and from natural lipocalin proteins, respectively. The concept of engineering robust protein scaffolds for novel binding functions emerged 20 years ago, one decade after the advent of recombinant antibody technology.
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