No abstract

Strategies to promote axonal extension through a site of injury, including the provision of nervous system growth factors and supportive substrates, produce growth of axons, that is highly random and does not extend past the lesion site and into the host tissue (Brain Res. Bull 57 (6) (2002) 833). Physically guiding the linear growth of axons across a site of injury, in addition to providing neurotrophic and/or cellular support, would help to retain the native organization of regenerating axons across the lesion site and into distal host tissue, and would potentially increase the probability of achieving functional recovery. In the present study, a novel procedure was developed for using freeze-dry processing to create nerve guidance scaffolds made from agarose, with uniaxial linear pores. The hydrated scaffolds were soft and flexible, contained linear guidance pores extending through their full length, were stable under physiological conditions without chemical crosslinking, and could be readily loaded with diffusible growth stimulating proteins. r

While several strategies can stimulate axonal regeneration within a site of spinal cord injury, the growth of axons is generally disorganized and random. Biocompatible scaffolds that guide and maintain the native organization of axons regenerating through an injury site could be of importance in enhancing recovery of the nervous system after injury. Here we report a novel fabrication process for templated agarose nerve guidance scaffolds composed of uniaxial channels of precise diameter and wall thickness extending through their full length. When tested in an in vivo model of spinal cord injury, scaffolds exhibit excellent integration with host tissue and support linear axonal growth through their channels. Further, when loaded with bone marrow stromal cells genetically engineered to secrete brain-derived neurotrophic factor (BDNF), the number of linear penetrating axons is significantly enhanced. The templating process can be useful in fabricating nerve guidance scaffolds for both central and peripheral nerve injuries, or any materials application requiring a precise array of linearly oriented channels.

No abstract

Of critical importance in drug delivery and tissue engineering applications is the degradabilty of implanted polymeric materials. The use of peptide-derived crosslinkers in hydrogel design is a valuable approach by which polymeric carriers can be endowed with enzymatic degradability in a predictable, 'programmable' fashion. The solid-phase synthesis strategy described herein allows for an expeditious, flexible synthesis of bis-acrylamide-derivatized peptides with complex modifications, as exemplified by the incorporation of fluorophore and quencher moieties into a matrix metalloprotease (MMP)-degradable crosslinker. The crude synthetic product was obtained in high yield and purity, and purified by standard methods; it was then used directly for polymerization without the need for tedious and often non-chemoselective solution-phase modifications. Functional appendages incorporated for detection provided a direct, quantitative link between enzymatic activity and hydrogel degradation using routine methods for identification of optimal enzyme-specific degradability.