Mineralized collagen scaffolds for regenerative engineering applications.

Collagen is a primary constituent of the tissue extracellular matrix. As a result, collagen has been a common component of tissue engineering biomaterials, including those to promote bone regeneration or to investigate cell-material interactions in the context of bone homeostasis or disease. This review summarizes key considerations regarding current state-of-the-art design and use of collagen biomaterials for these applications. We also describe strategic opportunities for collagen biomaterials to address a new era of challenges, including immunomodulation and appropriate consideration of sex and other patient characteristics in biomaterial design.

Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties.

Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. We use tissue engineering approaches to recreate the three-dimensional tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived xenograft GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We propose a tumor specific combination treatment of HYAL and HAS inhibitors to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand - dependent signaling roles of hyaluronan in glioblastoma. Significance: The control of aberrant hyaluronan metabolism in the tumor microenvironment can improve the efficacy of current treatments. Bioengineered preclinical models demonstrate potential to predict, stratify and accelerate the development of cancer treatments.

Naturally derived biomaterials for addressing inflammation in tissue regeneration.

Tissue regeneration strategies have traditionally relied on designing biomaterials that closely mimic features of the native extracellular matrix (ECM) as a means to potentially promote site-specific cellular behaviors. However, inflammation, while a necessary component of wound healing, can alter processes associated with successful tissue regeneration following an initial injury. These processes can be further magnified by the implantation of a biomaterial within the wound site. In addition to designing biomaterials to satisfy biocompatibility concerns as well as to replicate elements of the composition, structure, and mechanics of native tissue, we propose that ECM analogs should also include features that modulate the inflammatory response. Indeed, strategies that enhance, reduce, or even change the temporal phenotype of inflammatory processes have unique potential as future pro-regenerative analogs. Here, we review derivatives of three natural materials with intrinsic anti-inflammatory properties and discuss their potential to address the challenges of inflammation in tissue engineering and chronic wounds.