**1. Introduction**

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154 Regenerative Medicine and Tissue Engineering

Today great hope is set on regenerative medicine in all medical fields. Leland Kaiser intro‐ duced the term "Regenerative Medicine" in 1992. He forecasted that a "new branch of medicine will develop that attempts to change the course of chronic diseases and in many instances will regenerate tired and failing organ systems" (Kaiser, 1992). Since then, scientists all over the world try to develop cell-based approaches to regenerate damaged tissues, or even substitute whole organs (Ehnert et al., 2009).

Degenerative disease of articular cartilage (AC), generically known as osteoarthritis (OA), is an irreversible evolution process towards terminal articular failure. Due to its high prevalence on population and its socioeconomic impact, this condition is of great con‐ cern, and this way more resources and effort are dedicated to the research on its develop‐ ment. Cartilage tissue engineering seeks to combine cells, biomaterial scaffolds, and bioactive signals to create functional tissue replacements to treat cartilage injuries or osteoarthritis (Song et al., 2004).

Cartilage degenerative disease, OA, is the end stage of several conditions such as trauma, inflammatory diseases, overweight etc. The fatalistic theory that states that it is impossi‐ ble to recover the cartilage once it has been damaged leads to the assumption that the progression to any form of OA is unavoidable (Fig. 1). The annual incidence of young adults suffering any cartilage injury in UK is 10000 and this figure is continuously increasing (NICE, 2008).

© 2013 López-Puerta et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Figure 1.** Osteochondral injury in a femoral head from a surgical intervention in our hospital

The new patient does not accept a reduction in his demands and quality of life because of the OA as the culmination of an articular injury during sport activity. On the other hand, a higher risk for developing degenerative disease and obesity, mainly knee arthritis, has been corre‐ lated. The symptomatic cohort of pain, swelling, range of motion diminution and loss of quality life can only be partially recovered by a total joint replacement (Fig. 2).

Unfortunately, joint replacement is neither a procedure free of complication nor a foreverrealistic solution. It is expected that by the year 2030 the number of total hip or knee replacement implanted annually will be respectively 1.8 and 7 times the current figures (Kurtz et al., 2007). It is doubted that such an economic impact could be ever be afford‐ ed. Finding an alternative option to manage these lesions will be a challenge and this must be closer to achieve an almost AC tissue able to bear the requirements of an active long period of life.

AC is a quite simple structure with scarce cellularity within an extracellular matrix (ECM). However, in spite of this simplicity, its structure and performance is very complex.

The ability of the AC to heal these injuries on its own is almost none. The lack of blood supply is the main handicap this tissue has at the time of healing. Without vessels the preliminary inflammatory step of the healing process is not possible. To start with, the dead tissue needs to be removed and the flood of new cells from the vascular stream is essential for this. Is the Articular Cartilage Regeneration Approachable Through Mesenchymal Stem Cells Therapies? http://dx.doi.org/10.5772/56298 157

**Figure 2.** Treatment of a OA by total joint replacement performed in our hospital

Furthermore, the cell mediators will not appear as the granulocytes are not present and the degranulation of these is its source. Secondly, the chondrocytes are well-differentiated cells with a limited capacity to produce ECM. This is sufficient to cover the necessities of a still cartilage turnover but not to cope with the healing of a traumatic defect.

In any case, if the trauma produces a lesion that breaches the subchondral plate, it allows access to the vascular network and the final produced tissue is made of collagen type I, more resistant to tension, instead of type II, more resistant to compression.

#### **1.1. How can this be sorted out?**

**Figure 1.** Osteochondral injury in a femoral head from a surgical intervention in our hospital

life can only be partially recovered by a total joint replacement (Fig. 2).

period of life.

156 Regenerative Medicine and Tissue Engineering

The new patient does not accept a reduction in his demands and quality of life because of the OA as the culmination of an articular injury during sport activity. On the other hand, a higher risk for developing degenerative disease and obesity, mainly knee arthritis, has been corre‐ lated. The symptomatic cohort of pain, swelling, range of motion diminution and loss of quality

Unfortunately, joint replacement is neither a procedure free of complication nor a foreverrealistic solution. It is expected that by the year 2030 the number of total hip or knee replacement implanted annually will be respectively 1.8 and 7 times the current figures (Kurtz et al., 2007). It is doubted that such an economic impact could be ever be afford‐ ed. Finding an alternative option to manage these lesions will be a challenge and this must be closer to achieve an almost AC tissue able to bear the requirements of an active long

AC is a quite simple structure with scarce cellularity within an extracellular matrix (ECM).

The ability of the AC to heal these injuries on its own is almost none. The lack of blood supply is the main handicap this tissue has at the time of healing. Without vessels the preliminary inflammatory step of the healing process is not possible. To start with, the dead tissue needs to be removed and the flood of new cells from the vascular stream is essential for this.

However, in spite of this simplicity, its structure and performance is very complex.

Several attempts have been made in order to repair the traumatic defect and to achieve a regeneration of the original injured cartilage.

A first group of interventions can be described as "marrow stimulating techniques". Drilling the defect beyond the subchondral plate is its essential and allowing a repair promoted by the bleeding from the subchondral bone creating a "super clot" its rationale (Mithoefer et al., 2005). The star cells here are the mesenchymal stem cells (MSCs) emerging with the hematoma and its subsequent proliferation and differentiation. Unfortunately, the final result is the promotion of a fibrous tissue not durable in time (Steret et al., 2004). Pridie et al. promoted this concept in 1959. Abrasion arthroplasty (Steret et al., 2004), microfracture (Steadman et al., 2003), or Autologous Matrix Induced Chondrogenesis (Gille et al., 2010) have been more recently developed with the same rationale.

In essence, previous treatments have attempted to promote the healing of the damaged reminding nature. That is to say, allowing the flood of blood from the inner areas of the subjacent bone. Unfortunately, this will promote a scar tissue that in the long run will be lost and the joint degenerative process will be stated (Kreuz et al., 2006).

In a second group of interventions, it is proposed the articular defect to be covered by a "replacement technique". In these, the defect is reshaped to a standard cylindrical way and substituted with a plug of osteochondral graft harvested from a non-weight bearing donor site. Using this technique two handicaps can be appreciated: the limited available graft and the morbidity of the donor site. Additionally, the differences in characteristics between the donor and the receiver areas may impede a complete integration. This may be the reason why the clinical results have not been in accordance with the initial enthusiasm (Mishima et al., 2008). Both, auto- and fresh allograft (Gross et al., 2002) have been attempted with the name of mosaicplasty. With the aim of avoiding the donor site morbidity, synthetic reabsorbable scaffolds have been used to fill up the osteochondral defect. A "toast and butter" cylinder, engineered mimicking components, bone and cartilage. In contrast with the graft, this scaf‐ fold will have osteoconductive properties instead and eventually resorb in 12 months. The pseudo-cartilage now created will bepoorly incorporatedandthe biomechanics willfail(Yasen et al., 2012).

The third group of proposed interventions are cellular-based. The aim in this alternative option is producing a regeneration of the cartilage mediated by the own patient chondrocytes. This is a two-stage procedure. During the preliminary intervention a biopsy from the cartilage is obtained and then the chondrocytes are isolated and cultured till the number of cells is about fifty folds. For the second intervention, *ex vivo* expanded chondrocytes are implanted in the damaged area. This procedure has evolved with the aim of getting a watertight seal environ‐ ment in order to receive the chondrocytes and avoid the leakage. First, it was attempted a sheet of periosteum, then a collagen gel and a collagen membrane has been developed. But, are the delivered chondrocytes, the MSCs coming from the subchondral bone or the cells evading from the layer of periosteum the source for promoting the repaired tissue?. In spite of the rationale of this techniques, the autologous chondrocytes implant has not finally reached the expected results, the final tissue obtained was fibrous instead of AC (Tins et al., 2005) and hence, the OA is once more the undesirable expected long-term result (Hunziker, 2002; Temenoff et al., 2000).
