**Author details**

Currently strategies in the design of biomimetic cartilage hydrogels are governed by the use of collagen Type I and derived from porcine small intestine submucosa implants. Although the chondrocytes typically lose their phenotype, the gene expression patterns changed when they are removed from their native environment, so give them a proper environment is necessary to keep its phenotype of chondrocytes in different populations to recreate the zonal organization [160]. In addition, biological trials *in vitro* be made taking into account the cell

According with reference [163] concentrations of 12-25 million cells/cm2 are needed to increase the matrix production and mechanical properties of human adult chondrocytes under static conditions. Nevertheless, material researches are focus on fabrication of three-dimensional artificial arrays in form of hydrogels using macromolecules present in the cartilage interterritorial matrix and trying to mimic the distinct cartilage zonal [160]; however, no substantial

Others approaches in cartilage tissue engineering are the use of hydrogel culture employed mesenchymal stem cells (MSCs) and the use of bioreactors in order to provide the necessary biochemical and biomechanical stimulations to enhance chondrogenesis [164,165]. Due to the many mentioned limitations related to chondrocyte sources, there is much effort to explore better alternative cell sources. Desirable characteristics for such sources include accessibility, availability, and chondrogenic capacity. Consequently, stem cells such as adult mesenchymal stem cells (MSCs) have emerged as promising cell sources for articular cartilage tissue engineering. Chondrogenic potentials of MSCs from different tissues have also been investi‐ gated and compared. Specifically, MSCs from bone marrow are the most popular considering they are easily harvested (via the iliac crest) and have good chondrogenic potential. Many in vitro and in vivo studies have revealed promising results of marrowderived MSCs combined with various biomaterials or growth factors for repairing cartilage defects [164,166]. Recently, Johnson et al. describe the discovery and characterization of kartogenin, a small molecule that induced stem cells to take on the characteristics of chondrocytes and improves joint function and promotes the regeneration of cartilage in vivo in two rodent models of chronic and acute

Mechanical stresses are an important factor of chondrocyte function as they stimulate them to increase the synthesis of ECM components. In cartilage culturing processes the main types of mechanical forces currently being investigated are hydrostatic pressure, direct compression,

Finally, to better recapitulate the ECM environment for cartilage tissue engineering, research‐ ers have to introduce several biological signals, including chondroitin sulfate (CS), hyaluronic acid (HA), and collagen type I and II, into tissue-engineered scaffolds to encourage tissue specificity [169]. CS, hyaluronic acid, and collagen type II have been shown to promote or enhance chondrogenesis of mesenchymal stem cells (MSCs) in hydrogel-based culture systems. In addition to the physical cues of native matrix, cells are exposed to an array of

biological cues throughout the ECM that direct cellular behavior.

density for each zone [161,162].

384 Regenerative Medicine and Tissue Engineering

joint [166].

shear environments [167, 168].

data of the formation of cartilage are reported.

Zaira Y. García-Carvajal1 , David Garciadiego-Cázares1 , Carmen Parra-Cid1 , Rocío Aguilar-Gaytán1 , Cristina Velasquillo 3 , Clemente Ibarra1,2 and Javier S. Castro Carmona4

1 Tissue Engineering, Cell Therapy and Regenerative Medicine Unit. Instituto Nacional de Rehabilitación, Secretaria de Salud. Mexico city, Mexico

2 Orthopaedic Surgery and Arthroscopy Servicie, Instituto Nacional de Rehabilitación, Sec‐ retaria de Salud. Mexico city, Mexico

3 Biotechnology Laboratory. Centro Nacional de Investigación y Atención al Quemado. In‐ stituto Nacional de Rehabilitación, Secretaria de Salud. Mexico city, Mexico

4 Instituto de Ingenieria y Tecnologia. Universidad Autónoma de Ciudad Juárez, Juarez City, Chihuahua, Mexico
