**8. Current clinical applications of multiphase designs**

The restoration of osteochondral tissue damage should be focused on the physiological features and the structure of the tissues that make it up (cartilage and bone), considering the different microenvironments that coexist in the native tissue. Through tissue engineering, multiphase designs have been developed, such as those discussed throughout this chapter that aspire to achieve this goal. Currently, the vast majority of them have been characterized in vitro; some already have an in vivo analysis in medium and large species, which brings them closer to clinical application. Although there are few multiphase designs that are currently available for a clinical application, they open an important direction for the rigorous evaluation of the designs found on this path.

 The Agili-C™ CartiHeal is a biphasic scaffold, which consists in of a cartilage phase made of hyaluronic acid and a bone layer comprised by crystalline aragonite (calcium carbonate based). After in vivo trial (goat model), this acellular scaffolds evidenced the potential to recruit cells from the host tissues, and enhanced hyaline cartilage formation and subchondral bone regeneration with

#### *Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based… DOI: http://dx.doi.org/10.5772/intechopen.84697*

a continuous maturation process without deterioration of the repair tissue after 12 months implanted in critical osteochondral defects [111]. For clinical trials, only one clinical case has been reported in a 47-year-old man with an injury Outerbridge grade IV. The lesion was treated successfully and resumed normal activity after 18 months. In a follow-up at 24 months, restoration of the articular surface was demonstrated by MRI [112]. Although the results were encouraging, the occupation of the patient (athlete) could have a positive influence on the observed result, this makes it necessary to develop clinical trials in a larger number of patients under controlled conditions in order to extrapolate the benefits to a wider segment of the population.

The TruFit™ CB is an acellular scaffold made from polylactide-coglycolide copolymer and a bone phase containing calcium sulfate. The scaffold was used at first by direct implantation for the treatment of focal articular surface defects, but it showed some controversial results [113]. Several clinical studies have described a slow chondral restoration in the area of the lesion, due to poor bone repair [119], together with the poor integration of the implant with the surrounding tissue [120]. The long-term follow-up (up to 2 years) have also been controversial; however, the constant was delayed formation of the subchondral lamina [121]. Due to these clinical data, a thorough review of TruFit™ CB�s design is necessary before arriving at an effective clinical application.

Maioregen™ is a triphasic biomimetic scaffold where the cartilage phase consists of equine type I collagen, an intermediate (tidemark like) layer consisting of type I collagen and magnesium-hydroxyapatite (Mg-HA), attached to the bone phase consisting of a mineralized blend of type I collagen and Mg-HA [116]. By preclinical tests on sheep and horses, it was possible to demonstrate the safety of the implant, but also that allowed the regeneration of the type II collagen-rich tissue after 6 months; this is a cell-free design [117, 118]. Throughout several clinical trials developed in such diverse populations ranging from 28 to 60 years and with a lesion size ranging from 1.5 to 6.0 cm2 , a good filling of the lesion and integration of the graft has been observed as a constant result. The evolution of the regeneration process has demonstrated the formation of subchondral bone and maturation of the chondral tissue in a period of 6 months. The evaluation by a high-resolution magnetic resonance imaging (MRI) shows the complete repair of the tissue in a period of 2 years in 66.7% of the cases treated, even in cases where the lesion involves the subchondral bone [116].
