During the past few years, the field of tissue engineering (TE) has been shifting from replacement to
regenerative strategies. Following this tendency, the requirements for biomaterials to be used in TE
have been also changing. While a few decades ago bioinert materials that do not provoke undesired
body responses were in the focus of material sciences, nowadays third generation biomaterials
mimicking the nanoscale mechanisms of the interactions between cells and their in vivo environment are
the target of material design. Although these mechanisms involve different bioactive molecules, until
now mainly strategies involving small peptide epitopes that copycat specific sequences of complex
proteins have been exploited. The breakthroughs that such approaches brought to biomaterials and TE
fields are undeniable. Nevertheless, the important role that carbohydrates play in tissue structuring and
function is still poorly explored and exploited in this context and we believe that this is one of the
missing pieces in the TE puzzle. Carbohydrates are an integral part of our life. We are literally covered
by them: from bacteria to mammalian cells, the molecular landscape of the cell surface is coated with
sugars forming the so-called glycocalyx. This strategic placement of the sugars makes them crucial for
the development, growth, function and/or survival of an organism. It is believed that the structural
diversity of carbohydrates is the key for understanding and controlling those processes because of the
huge number of ligand structures, which sugars can display in molecular recognition systems. However,
their main advantages: the intricacy and the large natural diversity have turned against the scientists
and have hampered their study. As a result, the field of glycomics is much less developed compared to
its counterparts genomics and proteomics within TE. Recent advances in carbohydrate synthesis,
sensing technologies and processing methodologies are inducing rapid changes in this field and will be
discussed in this paper. The use of carbohydrates as an interrogation and modulation tool for better
understanding of the complexity and dynamics of the natural three-dimensional environment of the
cells will be also focussed.