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The ultrastructure of articular cartilage is unique: chondrocytes are sparsely distributed within the surrounding matrix, maintaining minimal cell to cell contact. The interaction between cells, collagen framework, aggrecan, and fluid constitutes the complex ultrastructure of hyaline cartilage making its replacement or reproduction difficult. 1 New, ambitious regenerative procedures are emerging as potential therapeutic options for the treatment of chondral lesions, aiming to recreate a hyaline-like tissue thus restoring a biologically and biomechanically valid articular surface with durable clinical results.Autologous chondrocyte implantation (ACI) has been introduced in 1987 in Sweden, and in 1994 Brittberg et al 2 published the first clinical report showing satisfactory results for isolated femoral condyle lesions. Since then, several studies followed documenting both the production of a hyaline-like articular surface and good results in the majority of the patients at medium-long follow-up. Treatment indications have been broadened 3-5 and this cell-based technique has gained increasing interest worldwide. 6-10 The development of bioengineering technology further improved this regenerative treatment approach: essentially, transplanting biodegradable molecules that are used as temporary scaffolds for the growth of living cells. 11 Matrix-assisted ACI (MACI) techniques have been introduced in the clinical practice one decade ago, showing good clinical results while at the same time overcoming most of the concerns related to the firstgeneration ACI. 12 The use of cell-loaded scaffolds to regenerate a cartilage-like tissue presents advantages from both the biological and surgical point of view, thus aiming to further optimize this regenerative surgical procedure. Surgical TechniqueThe surgical technique of both ACI and MACI consists of two steps. The first one is an arthroscopic procedure where a Abstract Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results. Autologous chondrocyte implantation (ACI) has been developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented at medium-long follow-up. Bioengineering technology further improved this regenerative treatment approach to include matrix-assisted ACI (MACI) techniques. These procedures have been introduced in the clinical practice one decade ago, showing similar results while at the same time overcoming most of the concerns related to the first-generation ACI. The use of scaffolds to create a cartilage-like tissue in a three-dimensional culture system allows for the optimization of the procedure from both the biological and surgical point of view. However, despite thousands of treated patients and many published studies suggesting good clinical results and durability of these procedures, the properties of healthy, normal articular cartilage are still unmatched by an...

In recent years biological strategies are being more widely used to treat cartilage lesions. One of the most exploited novel treatments is Platelet-rich Plasma (PRP), whose high content of growth factors is supposed to determine a regenerative stimulus to cartilaginous tissue. Despite many promising in vitro and in vivo studies, when discussing clinical application a clear indication for the use of PRP cannot be assessed. There are initial encouraging clinical data, but only a few randomized controlled trials have been published, so it is not possible to fully endorse this kind of approach for the treatment of cartilage pathology. Furthermore, study comparison is very difficult due to the great variability in PRP preparation methods, cell content and concentration, storage modalities, activation methods and even application protocols. These factors partially explain the lack of high quality controlled trials up to now. This paper discusses the main aspects concerning the basic biology of PRP, the principal sources of variability, and summarizes the available literature on PRP use, both in surgical and conservative treatments. Based on current evidence, PRP treatment should only be indicated for low-grade cartilage degeneration and in case of failure of more traditional conservative approaches.

Several techniques have been used during the years to treat chondral and osteochondral lesions. Among them, the emerging trend in the field of osteochondral regeneration is to treat the entire osteochondral unit by implanting cell-free scaffolds, which provide a three-dimensional support for the cell growth and may act themselves as stimuli for an “in situ” tissue regeneration. Various multi-layered products have been proposed that mimic both the subchondral bone and the cartilaginous layer. Among these, three have currently been reported in the literature. One has been widely investigated: it is a nanocomposite three-layered collagen-hydroxyapatite scaffold, which is showing promising results clinically and by MRI even at mid-term follow-up. The second is a PLGA-calcium-sulfate bilayer scaffold: however, the literature findings are still controversial and only short-term outcomes of limited case-series have been published. The most recent one is a solid aragonite-based scaffold, which seems to give promising clinical and MRI outcomes, even if the literature is still lacking more in-depth evaluations.Even though the Literature related to this topic is quickly increasing in number, the clinical evidence it is still limited to some case series, and high-level studies are needed to better demonstrate their real effectiveness.

Background: Intra-articular microfragmented adipose tissue (MF-AT) injections have been proposed for the treatment of knee osteoarthritis (OA). Purpose: To compare a single injection of MF-AT or platelet-rich plasma (PRP) in terms of clinical outcomes and OA progression. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 118 patients with symptomatic knee OA were randomized to receive a single intra-articular injection of MF-AT or PRP. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the International Knee Documentation Committee (IKDC) subjective score, Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol visual analogue scale (EQ-VAS), EuroQol 5 dimensions (EQ-5D), and visual analogue scale (VAS) for pain. Primary outcomes were the IKDC subjective score and the KOOS pain subscore at 6 months. Knees were evaluated at baseline and at 6, 12, and 24 months with radiography and high-resolution magnetic resonance imaging (MRI) using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Results: Both MF-AT and PRP provided a statistically and clinically significant improvement up to 24 months. The improvement in the IKDC subjective score from baseline to 6 months was similar in both MF-AT (41.1 ± 16.3 to 57.3 ± 18.8) and PRP (44.8 ± 17.3 to 58.4 ± 18.1) groups ( P < .0005). The improvement in the KOOS pain subscore from baseline to 6 months was similar in both the MF-AT (58.4 ± 15.9 to 75.8 ± 17.4) and PRP (63.5 ± 17.8 to 75.5 ± 16.1) groups ( P < .0005). Overall, no differences were found between the MF-AT and PRP groups in terms of clinical outcomes, adverse events (18.9% and 10.9%, respectively), and failures (15.1% and 25.5%, respectively). Radiographic and MRI findings did not show changes after the injection. As a secondary outcome, more patients in the MF-AT group with moderate/severe OA reached the minimal clinically important difference for the IKDC score at 6 months compared with the PRP group (75.0% vs 34.6%, respectively; P = .005). Conclusion: A single intra-articular injection of MF-AT was not superior to PRP, with comparable low numbers of failures and adverse events and without disease progression. No differences were found in clinical and imaging results between the 2 biological approaches.