Award Winner in the Young Investigator Category, 2014 Society for Biomaterials Annual Meeting and Exposition, Denver, Colorado, April 16-19, 2014: Periodically perforated core-shell collagen biomaterials balance cell infiltration, bioactivity, and mechanical properties.

Orthopedic tissue engineering requires biomaterials with robust mechanics as well as adequate porosity and permeability to support cell motility, proliferation, and new extracellular matrix (ECM) synthesis. While collagen-glycosaminoglycan (CG) scaffolds have been developed for a range of tissue engineering applications, they exhibit poor mechanical properties. Building on previous work in our lab that described composite CG biomaterials containing a porous scaffold core and nonporous CG membrane shell inspired by mechanically efficient core-shell composites in nature, this study explores an approach to improve cellular infiltration and metabolic health within these core-shell composites. We use indentation analyses to demonstrate that CG membranes, while less permeable than porous CG scaffolds, show similar permeability to dense materials such as small intestine submucosa (SIS). We also describe a simple method to fabricate CG membranes with organized arrays of microscale perforations. We demonstrate that perforated membranes support improved tenocyte migration into CG scaffolds, and that migration is enhanced by platelet-derived growth factor BB-mediated chemotaxis. CG core-shell composites fabricated with perforated membranes display scaffold-membrane integration with significantly improved tensile properties compared to scaffolds without membrane shells. Finally, we show that perforated membrane-scaffold composites support sustained tenocyte metabolic activity as well as improved cell infiltration and reduced expression of hypoxia-inducible factor 1α compared to composites with nonperforated membranes. These results will guide the design of improved biomaterials for tendon repair that are mechanically competent while also supporting infiltration of exogenous cells and other extrinsic mediators of wound healing.

Human mesenchymal stem cell response to 444 ferritic stainless steel networks

The aim of this work is to improve bone-implant bonding. This can, potentially, be achieved through the use of an implant coating composed of fibre networks. It is hypothesised that such an implant can achieve strong peri-prosthetic bone anchorage, when seeded with human mesenchymal stem cells (hMSCs). The materials employed were 444 and 316L stainless steel fibre networks of the same fibre volume fraction. The present work confirms that hMSCs are able to proliferate and differentiate towards the osteogenic lineage when seeded onto the fibre networks. Cellular viability, proliferation and metabolic activity were assessed and the results suggest higher proliferation rates when hMSC are seeded onto the 444 networks as compared to 316L. Cell distribution was found uniform across the seeded surfaces with 444 showing a somewhat higher infiltration depth. Copyright © Materials Research Society 2013.

Inhibitory plasticity balances excitation and inhibition in sensory pathways and memory networks

Cortical neurons receive balanced excitatory and inhibitory synaptic currents. Such a balance could be established and maintained in an experience-dependent manner by synaptic plasticity at inhibitory synapses. We show that this mechanism provides an explanation for the sparse firing patterns observed in response to natural stimuli and fits well with a recently observed interaction of excitatory and inhibitory receptive field plasticity. The introduction of inhibitory plasticity in suitable recurrent networks provides a homeostatic mechanism that leads to asynchronous irregular network states. Further, it can accommodate synaptic memories with activity patterns that become indiscernible from the background state but can be reactivated by external stimuli. Our results suggest an essential role of inhibitory plasticity in the formation and maintenance of functional cortical circuitry.

Self-organization of reflexive behavior from spontaneous motor activity.

In mammals, the development of reflexes is often regarded as an innate process. However, recent findings show that fetuses are endowed with favorable conditions for ontogenetic development. In this article, we hypothesize that the circuitry of at least some mammalian reflexes can be self-organized from the sensory and motor interactions brought forth in a musculoskeletal system. We focus mainly on three reflexes: the myotatic reflex, the reciprocal inhibition reflex, and the reverse myotatic reflex. To test our hypothesis, we conducted a set of experiments on a simulated musculoskeletal system using pairs of agonist and antagonist muscles. The reflex connectivity is obtained by producing spontaneous motor activity in each muscle and by correlating the resulting sensor and motor signals. Our results show that, under biologically plausible conditions, the reflex circuitry thus obtained is consistent with that identified in relation to the analogous mammalian reflexes. In addition, they show that the reflex connectivity obtained depends on the morphology of the musculoskeletal system as well as on the environment that it is embedded in.