Injectable gels for tissue/organ repair

Abstract

Hydrogels are water-swollen polymer networks that are being developed for a range ofapplications, from tissue engineering to drug delivery. The last decade has seen widespreadadvances in the design of novel hydrogel systems, enhancing their functionality and utility inbiomedicine [1, 2]. Hydrogels exhibit high water content and can be tailored with respect tomechanical properties and degradability, and even with stimuli-responsive behaviors. Oneattractive feature of many hydrogel systems is that they are injectable, providing a means fornon-invasive delivery of hydrogels directly into voids or tissues [1, 2]. Hydrogels oftenassemble (transit from sol to gel) from hydrophilic precursors via a range of non-covalentand covalent mechanisms, including radical polymerizations and ionic crosslinking, and cangel from solutions that mix prior to injection or directly within a tissue [3]. Alternatively,shear-thinning hydrogels are also being developed that liquefy with shear during applicationand reassemble upon injection [4].There are a range of requirements in hydrogel design to make them feasible as injectablesystems. These include the ability to gel via some trigger when applied to the tissue, whichcan range from a chemical reaction due to the mixing of two components, the application oftemperature or light, or even changes in pH [1, 2]. It is important to also realize the clinicalcontext and the mechanism in which the gel can be delivered (e.g. direct injection orcatheter). The mechanism and rate at which gelation occurs must also be balanced with theapplication and goals of the material (e.g. too slow might lead to extensive materialdistribution, too fast might lead to gelation prior to reaching the desired site) and whether itcontains biological components (e.g. cells or growth factors) that might be harmed by aspecific process. Finally, the toxicity of not only the gel, but the various precursors must beconsidered in hydrogel design and application.This special issue includes a range of review and research articles related to variousaspects of injectable gels, from synthesis to applications in relevant animal models. Includedreviews are by world experts who have made significant advances in the synthesis andapplication of injectable gels themselves, and these reviews highlight unique needs of varioustissue systems from the perspective of engineered hydrogel design and delivery. First,Pakulska and colleagues [5] review the application of injectable hydrogels to the centralnervous system, primarily to deliver molecules and cells for tissue repair and to overcomesome of the transport limitations across the blood–brain barrier. Continuing in this area, butwith a focus on the peripheral nervous system, Lin and Marra [6] present a review oninjectable hydrogels for growth factor/cell delivery and to fill nerve guidance channels.Highlighting the unique mechanical and chemical requirements of the vocal fold, Bartlett andcolleagues [7] review recent literature on injectable gels that are being investigated for vocalfold regeneration and repair. Young and Christman [8] continue the focus on soft tissues byreviewing the application of injectable gels as soft tissue fillers, particularly in the area ofadipose tissue engineering. The final review by Amini and Nair [9] focuses on themusculoskeletal system with emphasis on injectable systems for bone and cartilage repair.Within this field, there is a focus on the further development of a range of materialsystems that have a history of established clinical use and biocompatibility (e.g. alginates,fibrin); yet, progress is still being made on new material systems that exhibit addedfunctionality. This next set of papers focuses on new hydrogel development and thecharacterization of hydrogel properties. First, Alves and colleagues [10] describe their workwith poly(vinyl alcohol) hydrogels formed through hydrazone bonds and the resultinggelation, swelling and degradation properties. Next, Lin et al [11] describe theircharacterization of composites of hydroxyapatite and thermosensitive PLGA-g-PEGhydrogels for bone tissue engineering. Desai and collegues [12] then describe theencapsulation of cells within radically polymerized hydrogel systems and the influence ofvarious design parameters on cellular viability. These examples represent the wide variety ofproperties available in hydrogel systems.Toward specific applications in tissue repair, the last articles focus on issues related tospecific tissue models. First, Srinivasan et al [13] develop hyaluronic acid hydrogelsmodified with the molecule perlecan for controlling growth factor delivery in a model ofosteoarthritis. Erickson and colleagues [14] investigate neocartilage formation in modelcartilage defects using hyaluronic acid hydrogels as carriers for stem cells. Skaalure andco-workers [15] also present work toward cartilage repair, namely the encapsulation ofchondrocytes of various age in degradable poly(ethylene glycol) hydrogels. Turning toanother musculoskeletal application in bone repair, Dumas and co-workers [16] report ontheir work with injectable polyurethane composites for the repair of calvarial defects. Finally,poly(vinyl alcohol) composites are investigated by Ambrosio et al [17] for tunability inproperties and for repair of bone defects in femurs. These examples illustrate uniquetissue-specific considerations in injectable gels for various applications in tissue repair.