Articular Cartilage's Struggle with Regeneration


Tissue Engineering Treatments

Scaffold Based Approaches

One of the first tissue engineering-based techniques for healing cartilage injuries is the scaffold-based approach.Scaffolds are engineered structures that are designed to allow cells to grow on them or inside them. Approaches using scaffolds use biocompatible materials with cells seeded throughout the structure. Ideally, scaffolds should have a network that allows for movement of nutrients and waste, be biodegradable, and help cells proliferate and attach in the joint. Scaffolds can be either applied in vitro or in vivo, meaning in the lab or in the body, respectively. In vitro scaffolds are simple to produce, as they are just there to assist cells in growing new tissue. In vivo scaffolds must be able to withstand the intense mechanical forces present in the joint, and also be able to degrade as the tissue grows so as not to hinder collagen growth and cell signaling.

 Scaffoldless Approaches

While scaffolds are a useful tool in engineering tissue, they also have negative effects, such as slow degradation, toxicity, and hindrance of cell signaling. Alternatives to scaffold-based approaches exist, such as the self-assembly process. This process produces cartilage in vitro with properties that approach those of native tissue, including high levels of GAG (glycosaminoglycan) and collagen, which in turn gives the cartilage mechanical properties almost as robust as native tissue.

The self-assembly process exhibits four distinct phases which, in many ways, remind us of the development process of articular cartilage. First, the cells aggregate and interact with each other; then they move apart and make an immature-type of collagen; at the end the tissue produced by the cells is mature and has properties that approach those of native articular cartilage.

Stem Cells

Due to the difficulties with chondrocyte sources for cells, stem cells are a promising solution to healing articular cartilage. Stem cells are able to generate multiple daughter cells identical to the parent cell, all of which are undifferentiated, meaning they have the potential to turn into other types of cells. Embryonic Stem Cells (ESCs) show the most promise as they have unlimited differentiation potential and unlimited proliferation which would make them ideal for regenerating large areas of damaged tissue, but there is a major problem with ESCs; there is widespread opposition to their use, mostly for religious, moral, and ethical reasons (please see section "controversies" for a more detailed discussion). Adult mesenchymal stem cells (MSCs) are another candidate for cartilage engineering, as they do not have the social stigma of embryonic stem cells and can be derived from bone, adipose tissue (fat), and skin tissue, making them easy to obtain. Additionally, they are capable of turning into cartilage, as well as muscle and bone. When subjected to certain chemical and mechanical factors, MSCs differentiate into chondrocytes.  However, MSCs can not proliferate indefinitely as do ESCs, making them a less desirable source. Furthermore, researchers have not as of yet been able to use any stem cells to tissue engineer articular cartilage that is on par with native cartilage.

 

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