The molecular and physical information coded within the extracellular milieu is informing the development of a new generation of biomaterials for tissue engineering. Several powerful extracellular influences have already found their way into cell-instructive scaffolds, while others remain largely unexplored. Yet for commercial success tissue engineering products must be not only efficacious but also cost-effective, introducing a potential dichotomy between the need for sophistication and ease of production. This is spurring interest in recreating extracellular influences in simplified forms, from the reduction of biopolymers into short functional domains, to the use of basic chemistries to manipulate cell fate. In the future these exciting developments are likely to help reconcile the clinical and commercial pressures on tissue engineering.

The field of tissue engineering places complex demands on the materials it uses. The materials chosen to support the intricate processes of tissue development and maintenance need to have properties which serve both the bulk mechanical and structural requirements of the target tissue, as well as enabling interactions with cells at the molecular scale. In this critical review we explore how synthetic polymers can be utilised to meet the needs of tissue engineering applications, and how biomimetic principles can be applied to polymeric materials in order to enhance the biological response to scaffolding materials (105 references).

The development of bone replacement materials is an important healthcare objective due to the drawbacks of treating defects with bone autografts. In this work we propose a bone tissue engineering approach in which arginine-glycine-aspartic acid (RGD)-modified alginate hydrogels are crosslinked with bioactive strontium and zinc ions as well as calcium. Strontium was chosen for its ability to stimulate bone formation, and zinc is essential for alkaline phosphatase (ALP) activity. Calcium and strontium gels had similar stiffnesses but different stabilities over time. Strontium gels made with alginate with a high percentage of guluronic acid residues (high G) were slow to degrade, whereas those made with alginate rich in mannuronic acid (high M) degraded more quickly, and supported proliferation of Saos-2 osteoblast-like cells. After an initial burst, strontium release from alginate gels was steady and sustained, and the magnitude of release from high M gels was biologically relevant. Saos-2 cultured within alginate gels upregulated the osteoblast phenotypic marker genes RUNX2, collagen I (COL1A1) and bone sialoprotein (BSP), and ALP protein activity was highest in alginate gels cast with strontium ions. This strategy has the potential to be combined with other alginate-based systems for bone tissue engineering, or adapted to other tissue engineering applications.