Building Biocompatible Hydrogels for Tissue Engineering of the Brain and Spinal Cord

Abstract

Tissue engineering strategies employing biomaterials have made great progress in the last few decades. However, the tissues of the brain and spinal cord pose unique challenges due to a separate immune system and their nature as soft tissue. Because of this, neural tissue engineering for the brain and spinal cord may require re-establishing biocompatibility and functionality of biomaterials that have previously been successful for tissue engineering in the body. The goal of this review is to briefly describe the distinctive properties of the central nervous system, specifically the neuroimmune response, and to describe the factors which contribute to building polymer hydrogels compatible with this tissue. These factors include polymer chemistry, polymerization and degradation, and the physical and mechanical properties of the hydrogel. By understanding the necessities in making hydrogels biocompatible with tissue of the brain and spinal cord, tissue engineers can then functionalize these materials for repairing and replacing tissue in the central nervous system.

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

“…For biomaterial implants containing a large number of transplanted cells, this microglial activity surrounding a graft may or may not be beneficial depending on whether the microglia are assisting microvessel formation thus promoting a new blood supply to the graft, or clearing foreign material. However, the glial scar formed around an injury to the CNS by reactive astrocytes [18,19], including an injury left by a needle tract [16,20,21], is broadly considered to hinder axon growth and thus would hinder the ability of the graft to integrate with the host tissue during neuron replacement therapies for PD. Thus a polymer designed to reduce the reactivity of astrocytes may be beneficial, but it is not clear how this could inherently be achieved.…”

Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

“…While the hydrogels used in these two studies are very similar in chemistry, neither study provides enough detail about the tunable properties to be independently replicated. Hydrogel chemistry and subsequent physical and mechanical properties all have unique contributions to successful tissue engineering, specifically with regard to the reaction of the host tissue to the hydrogel and how replacement cells respond to hydrogel encapsulation (Aurand et al, 2012a,b). A comprehensive exploration of hydrogels well suited for neural tissue engineering, composed of commercially available materials with defined tunable properties may help standardize the use of hydrogels for neural tissue repair.…”

“…HA is the main polymer backbone of the extracellular matrix (ECM) of the brain and is degraded by hyaluronidases produced by both neurons and glia in vivo (Al'Qteishat et al, 2006; Lindwall et al, 2013). Biologically inert PEG provides additional control over hydrogel physical properties and helps to enhance functionality through prefabrication of more complex polymers, allowing for the attachment of cells or incorporation of growth factors or drugs (Aurand et al, 2012a,b; Burdick et al, 2006; Lampe et al, 2011; Lin and Anseth, 2009; Lin et al, 2009, 2011; Sawhney et al, 1993; Young and Engler, 2011). Our study employs only these two components, without further modifications, to assess baseline biocompatibility and explore how changes in hydrogel polymer ratio and subsequent physical and mechanical properties affect the fate of encapsulated neural progenitor cells (NPC).…”

“…Hydrogel biocompatibility is improved when the mechanical properties of the hydrogel are matched to the host tissue (Aurand et al, 2012a,b; Banerjee et al, 2009; Engler et al, 2006; Georges et al, 2006; Saha et al, 2008; Seidlits et al, 2010; Teixeira et al, 2009). Since tissue-matching is an important quality of a successful hydrogel, we investigated the fate of both fetal- and adult-derived NPC in twenty-five different HA and PEG hydrogels.…”

Selective comparison of gelling agents as neural cell culture matrices for long-term microelectrode array electrophysiology

“…Apart from their biomedical use (e.g., contact lenses, wound dressings, drug delivery devices (Caló and Khutoryanskiy, 2015)), hydrogels have found their way into cell culture labs (Altmann et al, 2009;Andersen et al, 2015;Tibbitt and Anseth, 2009) and tissue engineering (Baroli, 2007;Kim et al, 2011;Leal-Egaña et al, 2013;Hunt et al, 2014). In the latter context, they serve as circuit reconstruction scaffolds for the timed orchestration of events in (neuro)development, as drug delivery devices or as cell encapsulation constituents for implantation (Aurand et al, 2012a(Aurand et al, , 2012bCarballo-Molina and Velasco, 2015;McMurtrey, 2015). There are several categories of gelling agents to choose from.…”