Recently, a biomimetic 3-layer scaffold, composed of type I collagen and nanostructured hydroxyapatite, was conceived with the aim of confining bone formation to the deepest portion of the construct without involving any superficial layer where the process of cartilaginous-like connective tissue formation should begin.

Preclinical studies showed good results in terms of both cartilage and bone tissue formation, and preclinical findings supported the use of the scaffold alone, suggesting that osteochondral regeneration occurred by harnessing and guiding the body’s self-regenerative potential. Thus, this cell-free scaffold was introduced into clinical practice with promising preliminary results in a heterogeneous patient population [13].

The osteochondral (OC) biomimetic scaffold (Fin-Ceramica Faenza SpA, Faenza, Italy) has a porous 3-D composite trilayered structure, which mimics the whole osteochondral anatomy. The cartilage-like layer, consisting of type I collagen, has a smooth surface. The intermediate layer (tidemark-like) consists of a combination of type I collagen (60%) and hydroxyapatite (40%), whereas the lower layer consists of a mineralized blend of type I collagen (30%) and hydroxyapatite (70%) reproducing the subchondral bone layer. The final construct was obtained by physically combining the layers on top of a Mylar sheet; the product was then freeze-dried and gamma-sterilized at 25 kGy.

A recent study published by Filardo analyzed the results in 27 consecutive patients who were affected by symptomatic knee OCD of the femoral condyles grade 3 or 4 on the ICRS scale and were enrolled and treated with the implantation of this 3-layer collagen-hydroxyapatite scaffold [13].

Patients were prospectively evaluated by subjective and objective International Knee Documentation Committee (IKDC) and Tegner scores preoperatively and at 1- and 2-year follow-up. An MRI was also performed at the two follow-up times. A statistically significant improvement in all clinical scores was obtained at 1 year, and a further improvement was found the following year. At the 2-year follow-up, the IKDC subjective score had increased from 48 preoperatively to 82, the IKDC objective evaluation from 40% to 85% of normal knees, and the Tegner score from 2.4 to 4.5.

The MRI evaluations showed good defect filling and implant integration but nonhomogeneous regenerated tissue and subchondral bone changes in most patients at both follow-up times. No correlation between the MOCART (magnetic resonance observation of cartilage repair tissue) score and clinical outcome was found.

The authors concluded that this biomimetic collagen-hydroxyapatite osteochondral scaffold, which requires a minimally invasive 1-step and a cell-free surgical approach, is a valid treatment option for knee OCD and might offer a good clinical outcome at 2-year follow-up, despite some postoperative adverse events such as swelling and stiffness in some patients; furthermore, less favorable findings were obtained with MRI evaluation.

Recent directions in cartilage repair are moving toward the possibility of performing one-step surgery: the scaffold-based approach represents a fascinating treatment option for osteochondral lesions, providing a structural basis for defect repair and stimulating the healing processes of damaged tissues. In this scenario, cell cultivation occupies a controversial role, and the use of cell-free scaffolds showed good results and avoided cell manipulation and its regulatory obstacles; several groups are analyzing the possibility of using MSCs with chondrogenic potential and growth factors (GF), thus avoiding the first surgery for cartilage biopsy and subsequent chondrocyte cell cultivation, with a significant reduction of the cost of the total procedure. MSCs represent an appealing tool for regenerative medicine, thanks to their unique characteristics and their self-renewal characteristics, their maintenance of “stemness” thus their potential for differentiation into cells forming multiple mesodermal tissues, and finally their trophic and immune-modulatory effects. Many authors demonstrated that MSCs have a self-renewal capacity and multi-lineage differentiation potential and they can be characterized by their cultivation behavior and their differentiation potential into adipogenic, osteogenic, and chondrogenic cells; therefore, once MSCs are cultured in the appropriate microenvironment, they can differentiate to chondrocytes and form cartilage [25, 44]. In this regard, the use of bone marrow aspirate concentrate (BMAC) cells, which contain multipotent MSCs and growth factors, can represent a possible alternative for regenerating cartilage tissue.

Recently we published a prospective nonrandomized study comparing a two-step technique (Hyalofast scaffold with cultivated chondrocytes) with a single-step technique using the same Hyalofast scaffold and BMAC implantation in a single-step technique, with no need for culture, thereby avoiding the expenditure for an extra procedure to retrieve chondral biopsy, decreasing the total costs of the procedure and donor site morbidity [20].

MRI showed complete filling of the defects in 76% of patients treated with MACI, and 81% of those treated with the BMAC-embedded scaffold. Histologic analysis consistently revealed hyaline-like features of restored cartilage after both treatments. We concluded that both techniques are excellent options for the treatment of large chondral lesions of the knee, with the BMAC technique being the preferrable option due to the one-step nature of the procedure.

MSC implantation offers potential advantages, including a single surgery, and no need of cartilage biopsy and cell cultivation, thus reducing the total cost of medical care.

Another recently published study was performed on athletes operated for grade IV cartilage lesions of the knee with MSCs covered with a Hyalofast membrane (Anika Therapeutics, Padova, Italy) [21]. In these patients bone marrow was harvested from the ipsilateral iliac crest and subjected to concentration and activation with Batroxobin solution (Plateltex®act-Plateltex SRO, Bratislava, SK) in order to produce a sticky clot, which was implanted into the prepared cartilage defect (Fig. 17.2). The patients followed the same specific rehabilitation program for a minimum of 6 months. Preoperative average values in the evaluated scores were significantly improved to final follow-up (p < 0.001). Patients younger than 45 years and those with smaller or single lesions showed better outcomes. MRI showed good stability of the implant and complete filling of the defect in 80% of patients, and hyaline-like cartilage was found in the histological analysis of the biopsied tissue. Second-look arthroscopies in seven knees revealed a smooth, newly formed intact tissue continuous with the healthy cartilage in all the patients; no hypertrophy was identified. Four patients consented for a concomitant biopsy which was taken from regenerated tissue at the site of the treated chondral lesion; good histological findings were reported for the four specimens analyzed, which presented with many hyaline-like cartilage features. No adverse reactions or postoperative complications were noted.