Special Collection: Harnessing Topographical Cues for Tissue Engineering
Biomaterials, such as polymers from natural (e.g. collagen, fibrin; cartilage engineering) or synthetic (e.g. polylactic acid (PLA), polyglycolic acid (PGA); tendon engineering) origin or calcium phosphate ceramics (e.g. hydroxyapatite (HA), β-tricalciumphosphate (β-TCP); bone tissue engineering), play a pivotal role in the field of tissue engineering as their surface can influence cell behavior. Historically biomaterials primarily had a scaffolding function, but it is being increasingly appreciated that biomaterials can directly instruct cell behavior through their stiffness, micro/nano topography, surface chemistry, cell adhesivity, crystallinity, release dynamics, degradation-by-products, etc. Moreover, the interactions at the cell-biomaterial interface are a dynamic interplay of 'give-and-take' where the cell for example degrades the biomaterial and the degradation-by-products can influence cell behavior.
Despite the fact that it has been extensively shown that surface topographies greatly affect cell behavior, they have only been recently explored for applications in tissue engineering (first publication in Tissue Engineering in 2007). In this special collection, we will highlight papers that exploit the power of surface topography for applications in retinal regeneration (Yao et al.), nerve regeneration (Mobasseri et al.), cartilage repair (Joergensen et al.), bone repair (Yoon et al.), dermal wound healing (Muthusubramaniam et al.) and vascular scaffolds (Chaterji et al.). For example, Yao et al. fabricated a biodegradable polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. They showed that the PCL scaffolds induced the differentiation of mouse retinal progenitor cells towards a photoreceptor fate in vitro and that the tissue engineered constructs could be delivered into the subretinal space of mice with minimal disturbance. Moreover, the functional integration was assessed by the expression of photoreceptor markers (such as Crx, Recoverin, Rhodopsin). Yoon et al. demonstrated that microgrooves with radial arrangement more efficiently recruited osteoblasts, correlating with the upregulation of cell migration signaling molecules (such as E-cadherin, Rac1, PI3K). In vivo, these implants resulted in improved bone repair in mouse calvarial defect models. Interestingly, Chaterji et al. used nanotopographies to engineer an in vitro testing environment which is able to induce various vascular smooth muscle cell phenotypes corresponding to healthy, diseased and aged arterial beds.
To fully harness the potential of surface topographies, future research should address amongst others the challenges associated with topographical diversity, the combinatorial complexity and the underlying mechanisms of action. Firstly, most studies to date focus on limited topographical shapes such as pits, pillars or grooves. However, using computational tools, libraries of surface topographies can be designed and microfabricated to increase the diversity of patterns and the identification of hit surfaces (Unadkat et al., PNAS, 2011). Alternatively, diverse surface topographies can be inspired by nature-derived surface structures, such as shark skin which prevents bacteria attachment and biofilm formation (Green et al.). Secondly, only a small amount of biomaterial properties are typically analyzed simultaneously, neglecting potential synergies between the biomaterial properties (e.g. stiffness, surface topography, composition) as well as with the biochemical environment (e.g. growth factor concentrations). In this respect, the study of Chaterji et al. nicely shows the synergistic effects of nanotopographical cues and stiffness on vascular smooth muscle function. Due to the complex interplay between cells and substrates and the daunting number of ways in which biomaterials can be modified, a shift from the rational design of biomaterials towards combinatorial screening approaches, typically used in the pharmaceutical industry for drug discovery, is an exciting avenue to tackle this combinatorial complexity ('materiomics') (Cranford et al., Adv Mater, 2013). Finally, to further optimize current topographical designs, a fundamental understanding of the mechanisms of action underlying topography-induced cellular behavior is required. In this respect, Stukel et al. and Miyoshi et al. provide a nice overview of the state-of-the-art knowledge.
In conclusion, there are many stimulating ideas on how to diversify surface topographies and tailor them together with other biomaterial properties so that biomaterials can move from scaffolding materials towards true bio-active materials.