Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration.
Electrospinning is an attractive fabrication process providing a cost-effective and straightforward technic to make extra-cellular matrix (ECM) mimicking scaffolds that can be used to replace or repair injured tissues and organs. Synthetic polymers as poly (ε-caprolactone) (PCL) and poly (ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) have been often used to produce scaffolds due to their good processability, mechanical properties, and suitable biocompatibility. While synthetic polymers can mimic the physical features of native ECM, natural polymers like alginate are better suited to recapitulate its hydrated state or introduce functional groups that are recognized by cells (e.g., –NH2). Thus, this study aims at creating electrospun meshes made of blended synthetic and natural polymers for tissue engineering applications. Polyethylene oxide (PEO), PCL, and PEOT/PBT were used as a carrier of Alginate. Scaffolds were electrospun at different flow rates and distances between spinneret and collector (air gap), and the resulting meshes were characterized in terms of fiber morphology, diameter, and mesh inter-fiber pore size. The fiber diameter increased with increasing flow rate, while there was no substantial influence of the air gap. On the other hand, the mesh pore size increased with increasing air gap, while the effect of flow rate was not significant. Cross-linking and washing of alginate electrospun scaffolds resulted in smaller fiber diameter. These newly developed scaffolds may find useful applications for tissue engineering strategies as they resemble physical and chemical properties of tissue ECM. Human Dermal Fibroblasts were cultured on PCL and PCL/Alginate scaffolds in order to create a dermal substitute.
Biofabrication strategies have made significant steps toward overcoming the clinical challenges of peripheral nerve repair. Many activities have focused on emulating the structural features of native nerve tissue which promote nerve regeneration, resulting in the development of a variety of fabrication techniques. In article number https://doi.org/10.1002/adhm.201701164, Lorenzo Moroni and co‐workers discuss the most relevant approaches, highlight their biomimetic character, and assess performance in achieving nerve repair.
There are limited treatment options available upon diagnosis of dry age-related macular degeneration (AMD), a leading cause of blindness in older people, which progressively threatens central vision and quality of life. Community engagement has the potential to support 'positive health' of individuals with untreatable eye conditions. Eating for Eye Health is an award-winning public-engagement project that aims to raise awareness of research suggesting that nutrition might help protect against progression of AMD and to encourage patients to cook and eat antioxidant-rich food in a community environment. The project engaged patients who had a diagnosis of dry AMD through a focus group and a community cookery day organized in partnership with the healthy food outlet, Pod, and the Manor Gardens Community Kitchen Project, Islington, London. A focus group highlighted participants' potential barriers to engagement with research about lifestyle modification and identified that a co-designed community cookery project could help to address unmet needs for support. Individuals with dry AMD reported increased levels of confidence in cooking skills after participating in the community cookery day. The combination of these methods within the context of AMD highlights how a focus on patient needs and expectations can establish and grow mutually beneficial relationships. There is potential for Eating for Eye Health, or similar community kitchen approaches, to be implemented within the community setting through NHS 'social prescribing' initiatives. In conclusion, Eating for Eye Health is unique in its combination of elements of community consultative and collaborative forms of engagement. These methods could be adopted as part of Sustainability and Transformation Plans (STPs) in local health policy development in the community.
A growing focus and continuing challenge for biological sciences is creating representative in vitro environments to study and influence cell behavior. Here, we describe the synthetic recreation of the highly ordered extracellular matrix (ECM) of the peripheral nervous system (PNS) in terms of structure and scale, providing a versatile 3D culturing platform that achieves some of the highest in vitro neurite growth rates so far reported. By combining electrospinning technology with a unique multi-material processing sequence that harnesses intrinsic material properties, a hydrogel construct is realized that incorporates oriented 6 m-diameter microchannels decorated with topographical nanofibers. We show that this mimics the native PNS ECM architecture and promotes extensive growth from primary neurons; through controlled variation in design, we show that the open lumens of the microchannels directing rapid axon invasion of the hydrogel while the nanofibers provide essential cues for cell adhesion and topographical guidance. Furthermore, these microstructural and nanofibrillar elements enabled a typically bioinert hydrogel (PEGDA) to achieve similar neurite extension when compared to a biocompatible collagen hydrogel, with PEGDA-based devices approaching neurite growth rates similar to what is observed in vivo. Through the accessible fabrication approach developed here, multi-material scaffolds were designed with cell-relevant architectures ranging from meso-to nanoscale and shown to support nerve growth to mimic PNS regeneration, with potential for regenerative medicine and neural engineering applications.
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