Table 2.

Clinical studies of BMAC-enhanced marrow stimulation for articular cartilage repair.

Patient number	Defect location(s)	Defect type	Defect size	Additional treatment	Nature of biomaterials	Source of bone marrow	Concentration performed?	Method of concentration	Aspirate amount/defect	Study group(s)	Follow-up	Evaluation methods	Major findings	Ref.
11	Femoral condyle, patella	1 or 2 chondral defects, Outerbridge types III or IV	2–8 cm2	Microfracture	Type I/III porcine collagen matrix	(1) Iliac crest	Yes	BMA (24 ml) centrifuged (15 min) to obtain a concentrated phase containing mononuclear cells.	n.a.	(1) Microfracture + collagen membrane + BMAC	6 months	(1) FACS analysis	(1) More cells with MSC phenotype obtained from iliac crest than microfracture site.	[71]
						(2) Microfracture site						(2) Culture of bone marrow samples from iliac crest and microfracture site	(2) Only MSCs from bone marrow could be long-term propagated and efficiently differentiated in vitro.
												(3) Clinical evaluations: pain, adverse events	(3) No pain. No adverse events.
50	Patella, medial femoral condyle	Chondral defects, ICRS grade IV	Median lesion sizes of 4.5 or 6.5 cm2	Microfracture	Hyaluronic acid-based scaffold	Iliac crest	Yes	BMA (60 ml) centrifuged. Yield: cellular concentration ~6× baseline value.	n.a.	(1) Hyaluronic acid-based scaffold + BMAC (HA-BMAC)	2 and 5 years	(1) MRI	(1) 100% normal or nearly normal IKDC objective score at 2 years in HA-BMAC (microfracture 64%).	[72]
								Batroxobin enzyme used to activate the BMAC.		(2) Microfracture		(2) IKDC objective and subjective score	(2) HA-BMAC group maintained improved knee function at 5 years according to Lysholm, Tegner, IKDC objective and subjective scores.
												(4) KOOS	(3) Higher score for HA-BMAC group according to Tegner, IKDC objective, and KOOS scores.
												(5) Lysholm
												(6) Tegner
34	Talus	Osteochondral defects	0.5–2.2 cm2	Microfracture	n.a.	Iliac crest	Yes	n.a.	3 ml	(1) Microfracture	2.8–8.3 years	(1) FAOS pain subscale	(1) FAOS and SF-12 PCS score significantly improved in microfracture group after a mean of 6.4 years and in the microfracture + BMAC group after a mean of 4 years.	[73]
										(2) Microfracture + BMAC		(2) SF-12 PCS	(2) MOCART score in microfracture + BMAC group significantly higher than in microfracture group after 2 years.
												(3) MRI	(3) Per MRI less fissuring and fibrillation in the microfracture + BMAC group after 2 years.
12	Talus	Full-thickness chondral	1.0–3.9 cm2	Particulated juvenile articular cartilage (PJAC); subchondral drilling	Bovine type I collagen and glycos-amino-glycan	Iliac crest	Yes	BMA (60 ml) centrifuged. Yield: 6 ml of BMAC	6 ml	(1) Subchondral drilling + BMAC + collagen scaffold	2.1 years (range: 1.0–3.5 years)	(1) AOFAS score	Better clinical outcome for the subchondral drilling + PJAC group according to higher AOFAS and FAAM scores after 2 years.	[74]
										(2) Subchondral drilling + PJAC		(2) FAAM score
												(3) SF-12 score

AOFAS: American Orthopaedic Foot and Ankle Surgeons; BMA: bone marrow aspirate; BMAC: bone marrow aspirate concentrate; FAAM: Foot and Ankle Ability Measure; FACS: fluorescence-activated cell sorting; HA: hyaluronic acid; ICRS: International Cartilage Repair Society; IKDC: International Knee Documentation Committee; KOOS: Knee Injury and Osteoarthritis Outcome score; Lysholm: Lysholm Knee Questionnaire; MOCART: Magnetic Resonance Observation of Cartilage Repair Tissue; MRI: magnetic resonance imaging; MSC: mesenchymal stem cell; n.a.: not available; PJAC: particulated juvenile articular cartilage; Ref.: reference; SF-12: short form 12 general health questionnaire; SF-12 PCS: SF-12 physical component summary score; Tegner: Tegner activity scale.