**7.4 Cartilage repair**

*Regenerative Medicine*

**7.2 Shoulder disorders**

**7.3 Osteonecrosis**

all patients showed clinical improvement, with satisfactory results in 70.7% of patients [120]. Remarkably, the authors found that patients with inferior treatment results had a greater severity of OA prior treatment, as they were marked at Kellgren-Lawrence grade IV, suggesting that advanced OA may be more restrained to BMC therapy. The side effects encountered in this study, joint inflammation and pain, were in accordance with data from Rodriguez-Fotan [118]. Recently, a similar (retrospective) study was executed by Mautner and associates. Patients were prospectively treated either with bone marrow aspirate concentrate (BMAC) or micro-fragmented adipose tissue (MFAT) injections, for symptomatic knee OA [121]. The follow-up responses consisted of 76 patients (with 106 knees). The Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, Emory Quality of Life (EQOL) questionnaire, and VAS for pain were compared with baseline scores for all patients, and outcomes between BMAC and MFAT groups were evaluated. Data demonstrated a significant improvement in joint function and VAS pain scores after both MFAT and BMAC injections. No significant difference between the two autologous biological groups was demonstrating that BM- or adipose tissue-derived

ortho-biological injections resulted in similar functional improvements.

procedure, and no laboratory validation data were reported.

Lately, Darrow et al. reported on patients treated for shoulder osteoarthritis or rotator cuff tears (*N* = 50), with either BMC or BMA injections. Patients were grouped in receiving one or two injections [122]. Outcome reports included resting pain, active pain, upper extremity functionality scale, and overall improvement percentage. Data were compared to baseline and between the two groups. All patients had significant posttreatment improvements in resting pain, active pain, and functionality scores, when compared to baseline values. Patients receiving two treatments, average interval duration of 22 days, experienced statistically significant more improvements in active pain than the patients receiving one injection. There were no significant outcome differences between patients with a rotator cuff tear or OA. Unfortunately, no information was provided on the BMA and BMC

Philippe Hernigou, world renowned for treating femoral head osteonecrosis, advocates the use of autologous BMC cell therapies [123]. He described a substantial repair and stabilization of necrotic femoral heads with percutaneous injection of autologous BMC, in combination with surgical core decompression. In a later paper, he reviews three decades of BMC therapies in hip osteonecrosis, emphasizing the quality of the BMC and cellular competence and addressing the effects of BM cell concentrates on the microenvironmental changes within osteonecrotic bone [124]. Other groups reported on prospective randomized clinical trials for femoral head osteonecrosis, comparing surgical decompression alone versus decompression augmented by autologous BMC preparations. The biologics were implanted during the surgical decompression procedure. In one study, patients were evaluated using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index questionnaire, VAS pain index, and MRI. The mean WOMAC and VAS scores in all patients improved significantly (*P* < 0.001). Post-procedural MRIs showed a significant (*P* = 0.046) improvement in patients in whom the surgical procedure was combined with BMC [125]. In a similar study, a significant decrease in pain associated with a functional benefit lasting the entire observation period was observed in the BMC-treated patients. However, no difference in clinical outcomes between

**26**

Awad and associates recently published a meta-analysis on knee cartilage repair [127]. They conducted a systematic review using the PRISMA guidelines and the *Cochrane Handbook for Systematic Reviews of Interventions*. A meta-analysis was conducted to estimate the effect size for function and pain in 724 patients, with a mean age of 44.2 years. In this review, both cultured BM-MSCs and autologous noncultured BMC were used. All autologous BMC treatment specimens were prepared following a two-step centrifugation method. Their most important meta-analytic finding was that the administration of non-cultured, fresh, BMC significantly reduced pain and improved knee function. This might be induced by the heterogeneous composition of the non-cultured BMC, as all constituents will synergistically foster cartilage regeneration and local pain management. Furthermore, BMC holds a certain volume of autologous plasma which can function as a cellular scaffold with the advantage of a more sustained release, compared to a pure cultured MSC product.
