Cartilage functions as a pivotal part of the joint environment. Its unique mechanical properties allow consistent frictionless movement over a lifetime. However, cartilage is a poorly vascularized tissue with limited self-healing ability. Other than trauma and aging, degenerative osteoarthritis is the leading cause of cartilage defects. Cartilage injuries of the knee affect approximately 900,000 Americans annually, resulting in more than 200,000 surgical procedures (Cole et al. 1999). Chondral defects are seen in 34–62% of knee arthroscopies in young patients with a median age of 35 years old (Widuchowski et al. 2007).

Drug therapy and physiotherapeutic interventions at present can improve symptoms of joint dysfunction and relieve pain. Unfortunately, no clinical research studies to date have proven that any drugs have the ability to inhibit cartilage degradation or reverse the degenerative process. Operative treatments repair cartilage defects completely by fixing the detached cartilage fragment or by chondrocyte transplantation and tissue regeneration. Current surgical procedures include debridement/chondroplasty, bone marrow stimulation techniques (i.e., microfracture, drilling), osteochondral autografting/allografting, and cell based therapies using autologous chondrocyte implantation (ACI). Despite substantial differences in the complexity and technical application of each method, the ultimate goals of successful cartilage repair are reducing pain; improving symptoms and long-term function; preventing early osteoarthritis and subsequent total knee replacements; rebuilding hyaline cartilage instead of fibrous tissue; and preventing degeneration. Clinical studies have reported outcomes for each technique according to different lesion sizes and the age of the patients. Though short-term success and a low failure rate have been achieved by generations of ACI, the long-term effect of the procedure and the results of full-thickness defect repair are not clear (Harris et al. 2011).

Fortunately, emerging technologies and the next generation of cartilage tissue engineering provide hope. The major areas that investigators are studying include a tissue-specific cell source, a biocompatible scaffold, and an optimal in vitro culture environment with bioactive molecules to promote and control proliferation, cellular differentiation, and maturation. First of all, stem cells, especially adult stem cells with self-renewal and multi-lineage differentiation potentials, are a more accessible cell source with no ethical issues compared to embryonic stem cells. Among the adult stem cells, bone marrow derived stem cells (BMSCs) are the first and most widely investigated and adipose derived stem cells (ASCs) have gained more popularity recently due to ease of collection from liposuction (Hildner et al. 2011). Unfortunately, chondrogenically differentiated BMSCs become hypertrophic and eventually result in endochondral bone formation; ASCs have a limited ability toward chondrogenic differentiation. Recently, synovium-derived stem cells (SDSCs) have been suggested as a tissue-specific stem cell; they possess superior chondrogenic potential both in vitro and in certain in vivo states (Pei et al. 2008; Jones and Pei 2012). Secondly, extracellular matrix (ECM) is known as a key component of the stem cell niche in vivo. It functions as a reservoir for growth factors and provides natural and intrinsic cues to direct the remodeling process during cell differentiation. Decellularized ECM (DECM) has been successfully used as a scaffold in tissues such as adipose and organ regeneration, such as lung, heart, brain, liver, and bladder (Hoshiba et al. 2010). Most recently, decellularized stem cell matrix (DSCM) from SDSCs has been demonstrated to provide a three-dimensional substrate to enhance cell proliferation and chondrogenic potential, possibly by immobilized biomolecular signals. This chapter will focus on causes of cartilage defects, the current status of ACI based cartilage repair, matrix based next generation cartilage repair, and future prospects.