Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_998_Библиотеки_им_академика_М_И_Перельмана

mimic natural tissue mechanical properties (i.e., hardness or elasticity for bone or bladder, veins and arteries, or cartilage respectively). Recently, biomaterial design has reached the nanoscale level, granting the possibility to ne-tune their properties, better mirroring the interactions between cells and the extracellular matrix (ECM) within living organisms, generating more suitable and functional architectures, thus increasing the chances of obtaining concrete biomedical bene­ts. For instance, a good enhancement of cell adhesion, proliferation, and expression of matrix components has been achieved through simply increasing the nanoscaled roughness of the scaf­fold pore walls [5]. This represents the ground level of tuning of biomaterials, and a variety of parameters can be modulated to inuence cells behavior, comprising physical ones, such as mor­phology (i.e., bers, sponges), roughness, topol­ogy, and topography (both at the micro- and nanoscale), and mechanical ones (i.e., stiffness). Upon these premises, new smart biomaterials and biopolymers can be created, such as elastic degradable polymers or polymers with shape memory [6]. Signicant improvements have been made in recent years in understanding how physi­cal properties of biomaterials affect cellular bio­chemical responses. This is principally carried out through mechano-sensing, an active cellular pro­cess involving dynamic interplay between cells and their physical environment, and several stud­ies have shed light on how physical signals potently guide cell fate [7].

In addition to the tuning of nano- and micro­scaled physical, topographical, and mechanical properties, biomaterials can be functionalized with biological signals in order to obtain bioac­tive scaffolds. In this respect, the creation of a biologically active surrounding puts cells in a naturally mimicked or engineered environment towards which they are inherently sensitive and can respond with different and specic behaviors triggered even with epitopes at the molecular level. Thus, the incorporation of bioactive cues may foster the desired cellular response towards tissue regeneration. Several signaling (macro) molecules can be used towards this aim, such as bioactive peptides, whole proteins, or even car­bohydrates. In fact, a cell outer membrane is usu­ally covered by a forest of carbohydrate structures (known as the glycocalyx) and at least six differ­ent receptor systems, which can be activated by interactions with adjacent cells, secreted signal­ing molecules, and specic ligands within the ECM, triggering a plethora of biochemical events, comprising cell adhesion, proliferation, migration, organogenesis, and wound repair.

Carbohydrates in particular, in the form of com­plex polysaccharides or smaller epitopes, repre­sent a tremendous resource for regenerative medicine applications that can be exploited directly as building blocks for natural scaffolds or as signaling cues added to the scaffold to better drive cells behavior.

Beyond scaffold bioengineering, enormous advances in cell biology, above all the discovery of human embryonic stem cells (hESCs) [8] and induced pluripotent stem cells (iPS) [9], have strongly broadened the horizons of regenerative medicine. Plastic surgery may benet from regenerative medicine advancement in several elds of applications, such as burn care, nerve regeneration, breast reconstruction, wound heal­ing, scar treatment, hand and face transplanta­tion, bioprosthetic interfaces, bone regeneration, deformities treatments, and skin regeneration. In this chapter we will review recent advances of regenerative medicine based on carbohydrates, from scaffold design and bioactivation, to cell glycoengineering aspects, towards the modula­tion of cellular responses and behaviors.

First of all, any scaffold for tissue engineering needs to be biocompatible; cells must adhere, maintain their functions, and migrate onto the sur­face. After implantation, the scaffold or tissue­engineered construct must elicit a negligible immune reaction, in order to prevent severe inammatory responses that might reduce healing capacities or cause material rejection by the body.