Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review

Table 1 Studies evaluating concentrated bone marrow aspirate in the treatment of full thickness chondral lesions

Ref.	Tissue	BMAC preparation	Concen-tration	Study design/methods/follow up	Outcomes measured	Results	LOE
Enea et al[4]	Knee	60 mL BMA from iliac crest processed with MarrowStim Concentration Kit (Biomet) resulting in 3-4 mL of BMAC. Chondral lesion debrided and microfracture performed. Biocollagen MeRE collagen membrane (Bioteck) cut to match shape and immersed in BMAC until implantation. 10:1 mixture of 1-2 mL fibrin glue and BMAC laid on lesion. Membrane inserted and placed. 2-3 mL of fibrin glue-BMAC injected over and left to solidify	NS	n = 9. Arthroscopic microfracture covered with collagen membrane immersed in autologous BMAC from iliac crest. Follow up: 29 mo	Biopsy cartilage evaluated by surgeon using criteria of international cartilage repair society. The following items were utilized: Cartilage repair assessment, MRI, IKDC, Lysholm, VAS (pre and post op), Tegner (pre and post op). Four patients had second look arthroscopy and biopsy	Significant clinical improvement (P < 0.005). Cartilage macroscopic assessment at 12 mo revealed all repairs appeared almost normal. Histo-analysis showed hyaline-like cartilage repair in 1 lesion, fibrocartilaginous repair in 2 lesions and a mixture of both in 1 lesion. Post op MRIs (6-9 mo out) all showed reconstitution of original cartilage. Bone marrow edema and/or subchondral irregularities observed in all cases. Non-homogeneous cartilage signal and fissuring observed in 2 of 3 cases	IV
Enea et al[5]	Knee	60 mL of BMA from the iliac crest was obtained and processed with MarrowStim Concentration Kit (Biomet) to obtain 3-4 mL of BMAC. Cartilage was treated with arthroscopic microfracture and the defect was covered with PGA-HA scaffold matrix (Chondrotissue) seeded with autologous BMAC. 10:1 mixture of 1-2 mL of fibrin glue and BMAC was then applied to lesion bed. PGA-HA soaked in BMAC was then applied with 2-3 mL additional fibrin glue-BMAC mixture dispersed over the matrix until solidification at 2-3 min	NS	n = 9 (Outerbridge type III/IV) Consecutively treated with arthroscopic Polyglycolic acid/hyaluronan - covered microfracture and BMAC. Follow up: 22 mo	Clinical scoring, IKDC, Lyshold, VAS, Tegner, cartilage microscopic examination at 12 mo, MRI at 8-12 mo post op. 5 patients underwent second look and 2 had biopsy	All patients but one showed improvement in clinical scoring from pre-op sto last follow-up (22 mo). All other variables increased from baseline to latest follow-up. Nineteen cartilage exams appeared normal, three almost normal, and one abnormal at 12 mo. Histo showed hyaline-like cartilage repair tissue formation in one case. MRI showed complete defect filling	IV
Gigante et al[6]	Knee	NA	NA	n = 5. MACI augmented with BMAC	Second look arthroscopy biopsy, CRA, ICRS II Visual Histological Assessment Scale	Normal ICRS/CRA at arthroscopic evaluation and had mean overall histological ICRS II of 59.8 ± 14.5. Hyaline-like matrix only found in one case. Mixture of hyaline/fibrocartilage was found in one case and fibrocartilage was found three cases	IV
Gobbi et al[7]	Patello-femoral	60 mL of BMA from ipsilateral iliac crest concentrated by BMAC Harvest Smart PreP2 system to obtain concentration of BMC 4-6 times baseline value	4-6 × baseline	(1) MACI n = 19; (2) BMAC n = 18. Both with HYAFF1 scaffold. Follow up: 3 yr	XR, MRI, IKDC score, KIOOS score, VAS, Tegner	Both groups showed significant improvements in all scores from preop to final follow up (P = 0.002). There was no difference between the two groups except in the IKDC subjective scores which favored BMAC group (P = 0.015). MRI showed complete filling of defect in 76% of MACI and in 81% of BMAC	III
Gobbi et al[8]	Knee	60 mL of BMA from ipsilateral iliac crest concentrated by BMAC Harvest Smart PreP2 system to obtain concentration of BMC 4-6 times baseline value. Activated using batroxobin enzyme to form sticky clot. Implanted and covered with collagen-based membrane scaffold (ChondroGide) and sealed with fibrin glue (Tissucol)	4-6 × baseline	n = 25. Cartilage transplantation with mulipotent stem cells and collagen type I/III matrix	XR, MRI, VAS, IKDC, KOOS, Lysholm, Marx, Tegner	Significant improvement at follow up across all measures. < 45-year-old and smaller lesions = better results. MRI = good stability of implant, hyaline-like cartilage found is histo analysis of biopsied tissue	IV
Gobbi et al[9]	Knee	60mL BMA from ipsilateral iliac crest (PreP2) and concentrated to 4-6 times baseline value, after activation with batroxobin enzyme (Plateltex Act) and pasted into lesion Covered with collagen type I/III matrix (Chondro-Gide) and sealed with fibrin glue (Tissucol)	4-6 × baseline	n = 15. One step surgery with BMAC and Collagen I/III matrix (chondro-gide)	XR, MRI at 1 and 2 yr. VAS, IKDC, KOOS, Lysholm, Marx, SF-36, Tegner at 6, 12, 24 mo. 3 had second look biopsy	Significant improvement at follow up across all measures (P < 0.0005). Single lesion and smaller lesions had better improvement. MRI showed greater hyaline-like tissue in all patients. Hyaline-like cartilage on histology in 3 biopsies	IV
Krych et al[10]	Distal femur	NS	NS	(1) n = 11 control scaffold; (2) n = 23 scaffold + PRP; (3) n = 12 scaffold + BMAC. Follow up: 12 mo	MRI, T2 mapping	BMAC and PRP groups had superior cartilage infill (P = 0.002, P = 0.03). BMAC demonstrated mean T2 value closer to that of superficial hyaline cartilage (P = 0.01)	III

BMA: Bone marrow aspirate; NS: Not significant; CRA: Cartilage repair assessment; MRI: Magnetic resonance imaging; MACI: Matrix-induced autologous chondrocyte implantation; PRP: Platelet-rich plasma.