Figure 2. Advanced bioengineering concepts using biomaterials to control cell behavior (A).

The extracellular matrix of native connective tissue is highly dynamic and supports resident cells through presentation of biological and biophysical cues. (B) Biomaterials can recreate aspects of the tissue-specific microenvironment with biochemical signals to mimic cell-ECM and cell-cell interactions or to allow encapsulated cells to actively interact and integrate with their matrix environment. (C) Biomaterials can also be engineered to release chemo-attractive cytokines (e.g. stromal cell-derived factor 1α (SDF- 1α)) that enable migration of resident cells (e.g. mesenchymal stromal cells (MSCs)) or direct cell behavior by controlled release of encapsulated biological factors (e.g. bone-morphogenetic protein (BMP), transforming growth factor-β (TGF-β)). (D) Scaffold microenvironments are further being developed to alter the healing niche, for example by inducing a specific anti-inflammatory immune response or by releasing cytokines (e.g. interleukin 4 (IL-4) that activate M2 macrophages and promote tissue repair.