Cartilage Tissue Engineering

Articular cartilage is a tissue which has a limited capacity to heal once injured. The damaged cartilage can be surgically operated with a goal to provide symptomatic relief for the painful patients. However, the cartilage damage tend to be progressive, especially in systematic disease called osteoarthritis.

A concept of replacing the damaged cartilage by implantation of isolated chondrocytes (1) or laboratory-fabricated tissue-engineered tissue has emerged during the last decades, and numerous efforts using chondrocytes or even differentiated stem cells with or without various types of three-dimensional scaffolds or hydrogels manufactured from natural of synthetic biomaterials (3). Although cartilage-type of tissue may form initially, the long-term stability of the repair-tissue is still a major challenge.

There are several environmental factors, which can be sensed by the chondrocytes affecting their metabolism and the assembly of the extensive amount of extracellular matrix of normal articular cartilage. First, the cartilage has no blood vessels, therefore, the chondrocytes depend on diffusion of nutrients and waste products, which also leads to decreasing low oxygen tension gradients in articular cartilage from the surface to deeper zones of cartilage. We have investigated whether low oxygen tension would be beneficial for in vitro chondrocyte phenotype and cartilage formation (4,5). Cartilage also has unusually high osmotic pressure, which obviously have impact on the metabolism of chondrocytes. Besides these factors, the chondrocytes face various types of mechanical loading.

The figure shows a schematic drawing of articular cartilage representing the collagen fibers as black strings, and the red colour represents the gradient of proteoglycans. Black and white image shows in white the areas where the collagen fibers are parallel to each other, and the two histological images display the intensity of proteoglycan and type II collagen staining, respectively.

This tissue assembly is important for the proper function of the articular cartilage, and apparently requires appropriate mechanical loading to build up correctly. During embryonic and fetal development, the chondrogenic cells assemble the cartilage alone, therefore, we have studied how the cartilage forms in scaffold-free conditions under different osmolarity and presence of chondrogenesis inducing transforming growth factor beta3 (6), but also tested whether cross-linked hyaluronan or self-assembling peptide enhance the cartilage formation (7). Also our study on the efficiency of centrifugal force on chondrogenesis was recently accepted for publication (8). 

Related articles

  1. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O,Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331: 889-895, 1994 [Pubmed] [Full text]

  2. Pulkkinen H, Tiitu V, Lammentausta E, Laasanen MS, Hämäläinen ER, Kiviranta I, Lammi MJ: Cellulose sponge as a scaffold for cartilage tissue engineering. Bio-Med Mater Engin 16: S29-S35, 2006 [Pubmed] [Full text]

  3. Lammi MJ, Piltti J, Prittinen J, Qu C: Challenges in fabrication of tissue-engineered cartilage with correct cellular colonization and extracellular matrix assembly. Int J Mol Sci 19: 2700, 2018 (review) [Pubmed] [Full text]

  4. Qu CJ, Pöytäkangas T, Jauhiainen M, Auriola S, Lammi MJ: Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension. Cell Tissue Res 337: 103-111, 2009 [Pubmed] [Full text]

  5. Qu C, Lindeberg H, Ylärinne JH, Lammi MJ: Five percent oxygen tension is not beneficial for the neocartilage formation in scaffold-free cell culture. Cell Tissue Res 348: 109-117, 2012 [Pubmed] [Full text]

  6. Ylärinne JH, Qu C, Lammi MJ: Hypertonic conditions enhance cartilage formation in scaffold-free primary chondrocyte cultures. Cell Tissue Res 358: 541-550, 2014 [Pubmed] [Full text]

  7. Ylärinne J, Qu C, Lammi MJ: Scaffold-free approach produces similar quality neo-cartilage tissues as HyStem™ and Hydromatrix™ scaffolds. J Mater Sci Mater Med 28: 59, 2017 [Pubmed] [Full text]

  8. Prittinen J, Ylärinne J, Piltti J, Karhula S, Rieppo L, Ojanen P, Korhonen RK, Saarakkala S, Lammi MJ, Qu C: Effect of centrifugal force on the development of articular neocartilage with bovine primary chondrocytes. Cell Tissue Res, epub ahead of print, 2018 [Pubmed] [Full text]

Last updated May 27, 2019