Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration

Abstract

Aging is a complex multifactorial process that results in tissue function impairment across the whole organism. One of the common consequences of this process is the loss of muscle mass and the associated decline in muscle function, known as sarcopenia. Aging also presents with an increased risk of developing other pathological conditions such as neurodegeneration. Muscular and neuronal degeneration cause mobility issues and cognitive impairment, hence having a major impact on the quality of life of the older population. The development of novel therapies that can ameliorate the effects of aging is currently hindered by our limited knowledge of the underlying mechanisms and the use of models that fail to recapitulate the structure and composition of the cell microenvironment. The emergence of bioengineering techniques based on the use of biomimetic materials and biofabrication methods has opened the possibility of generating 3D models of muscular and nervous tissues that better mimic the native extracellular matrix. These platforms are particularly advantageous for drug testing and mechanistic studies. In this review, we discuss the developments made in the creation of 3D models of aging-related neuronal and muscular degeneration and we provide a perspective on the future directions for the field.

Keywords: 3D muscular models; 3D neural models; aging; biomaterials.

Figure 1

Schematic diagram showing a comparison between healthy brain tissue (left) and brain tissue affected by either Alzheimer’s or Parkinson’s disease (right). Alzheimer’s is characterized by the formation of extracellular Aβ plaques and intracellular neurofibrillary tangles, while the main hallmark of Parkinson’s is the intracellular accumulation of α-synuclein in the form of Lewy bodies. Created with BioRender.com.

Figure 2

Schematic diagram showing the hierarchical organization of skeletal muscle tissue. Muscle is composed of multinucleated cells known as myofibers, which contain multiple myofibrils. The latter are comprised of a series of sarcomeres, the contractile unit of muscle tissue. The sarcomere is a highly organized structure formed of actin and myosin filaments, the main orchestrators of muscle contraction. Created with BioRender.com.

Figure 3

Schematic diagram of the neuromuscular junction (NMJ), which is formed of a motor nerve terminal, the synaptic cleft, and the innervated muscle fiber. The arrival of an action potential to the nerve terminal causes the opening of voltage-dependent calcium channels. The influx of calcium triggers the release of acetylcholine (ACh) from synaptic vesicles into the synaptic cleft. ACh diffuses through the basal lamina and binds acetylcholine receptors (AChRs) present in the post-synaptic element of the NMJ. The molecular events that are consequently triggered lead to the contraction of muscle tissue. Created with BioRender.com.