Researchers using the XSD 12-ID-B beamline at the APS have demonstrated an arrested phase separation mechanism for forming extremely stiff physical networks from elastin-like polypeptides (ELP) solutions.
High-performance biomaterials that are responsive, robust, and easy to formulate are critical to address challenges in tissue engineering and regenerative medicine. Synthetically simple biomaterials that can be formulated under mild conditions are highly desired for biomedical applications. For complex surgical interventions thought to be crucial for tissue regeneration, the chemistry, structure, and mechanical behavior of substrates must be suitable for clinical implantation and long-term performance under physiological conditions.
Formulation of tissue engineering or regenerative scaffolds from simple bioactive polymers with tunable structure and mechanics is crucial for the regeneration of complex tissues, and hydrogels from recombinant proteins, such as elastin-like polypeptides (ELPs), are promising platforms to support these applications. The arrested phase separation of ELPs has been shown to yield remarkably stiff, biocontinuous, nanostructured networks, but these gels are limited in applications by their relatively brittle nature. Here, a gel-forming ELP is chain-extended by telechelic oxidative coupling, forming extensible, tough hydrogels. Small angle scattering indicates that the chain-extended polypeptides form a fractal network of nanoscale aggregates over a broad concentration range, accessing moduli ranging from 5 kPa to over 1 MPa over a concentration range of 5–30 wt %.
These networks exhibited excellent erosion resistance and allowed for the diffusion and release of encapsulated particles consistent with a bicontinuous, porous structure with a broad distribution of pore sizes. Biofunctionalized, toughened networks were found to maintain the viability of human mesenchymal stem cells (hMSCs) in 2D, demonstrating signs of osteogenesis even in cell media without osteogenic molecules. Furthermore, chondrocytes could be readily mixed into these gels via thermoresponsive assembly and remained viable in extended culture. These studies demonstrate the ability to engineer ELP-based arrested physical networks on the molecular level to form reinforced, cytocompatible hydrogel matrices, supporting the promise of these new materials as candidates for the engineering and regeneration of stiff tissues.
Matthew J. Glassman, Reginald K. Avery, Ali Khademhosseini and Bradley D. Olsen, “Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds,” Biomacromolecules, Article ASAP, DOI: 10.1021/acs.biomac.5b01210, Published Online January 20, 2016.