Does progress in microfracture techniques necessarily translate into clinical effectiveness?

Table 1 Characteristics of included studies in the network meta-analysis, each row depicts the individual comparator arm in the studies included

Ref.	Country	Study design	Sample size		Treatment		Mean age		Female		Mean defect size		Follow-up (months)
			Control	Intervention	Control	Intervention	Control	Intervention	Control	Intervention	Control	Intervention
Volz et al[31], 2017	Germany	RCT	34	13	AMIC	Microfracture	40.0	36.5	7	3	3.9	2.9	60
Niemeyer et al[32], 2019	Germany	RCT	52	50	MACI	Microfracture	36.0	37.0	19	22	2.7	2.4	24
Fossum et al[33], 2019	Norway	RCT	21	20	ACI-C	AMIC	37.2	38.3	7	12	4.9	5.2	24
Ulstein et al[34], 2014	Norway	RCT	11	14	Microfracture	AOT	31.7	32.7	11	9	2.6	3.0	120
Visna et al[35], 2004	Czech Republic	RCT	25	25	Autologous chondrograft transplantation	Microfracture	29.4	32.2	7	9	4	3.3	12
Assche et al[36], 2010	Belgium	RCT	33	34	ACI-P	Microfracture	34.0	34.0	11	10	2.5	2.3	24
Saw et al[37], 2013	United States	RCT	24	25	Microfracture with HA	Microfracture with PBSC	42.0	38.0	17	15	NA	NA	18
Anders et al[38], 2013	Germany	RCT	22	8	AMIC	Microfracture	41.0	38.0	17	15	3.7	3.5	24
Lee et al[15], 2013	Republic of Korea	RCT	25	24	Microfracture	Microfracture with PRP	46.0	46.0	10	10	3.0	3.0	24
Brittberg et al[39], 2018	Sweden	RCT	65	63	MACI	Microfracture	38.0	34.0	23	20	5.1	4.9	60
Lim et al[40], 2012	South Korea	RCT	30	22	Microfracture	AOT	32.9	30.4	12	10	2.7	2.7	60
				18		ACI-P		25.1		8		2.8	60
Knutsen et al[41], 2007	Norway	RCT	40	40	ACI-P	Microfracture	33.3	31.1			5.0	5.0	60
Knutsen et al[42], 2016	Norway	RCT	40	40	ACI-P	Microfracture	33.3	31.1			5.0	5.0	180
Liu et al[43], 2021	Taiwan	RCT	10	5	Kartigen	Microfracture	54.8	67.8	5	3	2.9	1.0	24
Yoon et al[44], 2020	Republic of Korea	RCT	20	10	ACI-CCP	Microfracture	41.5	47.2	6	7	3.5	2.5	12
Kon et al[45], 2018	Italy	RCT	51	49	Collagen HA	Microfracture	34.0	35.2	15	18	3.4	3.4	24
Vanlauwe et al[46], 2011	Belgium	RCT	51	61	ACI-P	Microfracture	33.9	33.9	22	20	2.6	2.4	60
Stanish et al[20], 2013	Canada	RCT	41	39	Microfracture with BST-CarGel	Microfracture	35.1	37.2	18	14	NA	NA	12
Basad et al[47], 2010	Germany	RCT	40	20	MACI	Microfracture	33.0	37.5	15	3	7.0	7.0	24
Solheim et al[48], 2018	Norway	RCT	20	20	Microfracture	Mosaicplasty	35.0	31.0	6	6	4.0	4.0	180
Bisicchia et al[49], 2020	Italy	RCT	20	20	Microfracture with SVF	Microfracture	49.8	46.1	8	7	3.2	3.1	12
Saris et al[50], 2014	Netherlands	RCT	72	72	MACI	Microfracture	34.8	32.9	27	24	4.9	4.7	24
Saris et al[51], 2008	Netherlands	RCT	57	61	ACI-P	Microfracture	33.9	33.9	22	20	2.6	2.4	12
Saris et al[9], 2009	Netherlands	RCT	57	61	ACI-P	Microfracture	33.9	33.9	22	20	2.6	2.4	36
Qiao et al[52], 2020	China	RCT	10	10	Microfracture	Microfracture with HA	62.3	59.7	7	5	4.0	4.0	12
				10		Microfracture with MSC		62.0		7		4.0	12
Nguyen et al[53], 2017	Vietnam	RCT	15	15	Microfracture with SVF	Microfracture	58.6	58.2	12	12	NA	NA	18
Lim et al[54], 2021	Republic of Korea	RCT	43	46	Microfracture with MSC	Microfracture	55.3	54.4	28	30	4.9	4.0	60
Venosa et al[55], 2022	Italy	RCT	19	19	Microfracture with PRP	Microfracture with MSC	56.4	55.8	7	10	1.0	1.0	12
Shive et al[19], 2015	Canada	RCT	34	26	Microfracture with BST-CarGel	Microfracture	34.3	40.1	12	12	2.4	2.0	60
Koh et al[13], 2016	Republic of Korea	RCT	40	40	Microfracture with MSC	Microfracture	39.1	38.4	24	26	4.8	4.6	24
Knutsen et al[4], 2004	Norway	RCT	40	40	ACI-P	Microfracture	33.0	31.1	16	16	5.1	4.5	24
Kim et al[56], 2017	South Korea	RCT	14	14	Microfracture	Microfracture with Collagen	55.7	55.4	0	1	2.9	3.6	12
Kim et al[57], 2020	South Korea	RCT	48	52	Microfracture	Microfracture with Collagen	51.7	48.9	9	12	4.6	3.9	24
Kane et al[58], 2018	United States	RCT	21	9	Neocart	Microfracture	41.4	38.8	2	3	2.2	1.7	60
Ibarra et al[59], 2021	United States	RCT	24	24	MACI	Microfracture	33.7	35.8	7	10	1.9	1.7	72
Hashimoto et al[60], 2019	Japan	RCT	7	4	Microfracture with MSC	Microfracture	42.6	46.3	4	0	3.0	4.4	12
Gudas et al[61], 2006	Lithuania	RCT	28	29	AOT	Microfracture	24.6	24.3	10	12	2.8	2.7	36
Gudas et al[62], 2013	Lithuania	RCT	28	29	AOT	Microfracture	24.6	24.3	10	12	2.7	2.8	120
Gudas et al[63], 2005	Lithuania	RCT	29	28	Microfracture	AOT	24.3	24.6	12	10	2.8	2.7	36
Glasbrenner et al[64], 2020	Germany	RCT	12	12	Microfracture	Microfracture with BMAC	36.7	47.9	3	6	1.7	1.7	12
Dasar et al[65], 2016	Turkey	RCT	20	20	Microfracture	Carbon fibre rod	36.4	38.5	15	15	3.5	4.0.	24
Crawford et al[66], 2012	United States	RCT	21	9	NeoCart	Microfracture	41.0	39.0	2	3	2.8	2.5	24
Cole et al[67], 2011	United States	RCT	9	20	Microfracture	MACI	33.0	32.7	4	6	3.4	2.7	24
Chung et al[68], 2014	South Korea	RCT	24	12	Microfracture with BMAC	Microfracture	47.4	44.3	10	10	1.3	1.5	24

ACI: Autologous chondrocyte implantation; ACI-C: ACI with collagen cover; ACI-P: ACI with periosteal cover; AMIC: Autologous matrix induced chondrogenesis; BMAC: Bone marrow aspiration concentrate; CCP: Cultured chondrocyte pellet; HA: Hyaluronic acid; MACI: Matrix-induced autologous chondrocyte implantation; MFx: Microfracture; MSC: Mesenchymal stromal cell; NA: Not available; OAT: Osteochondral autograft/allograft transfer; PRP: Platelet-rich plasma; RCT: Randomized controlled trial; SVF: Stromal vascular fraction.

Table 2 Network meta-analysis summary and ranking of interventions based on the SUCRA scores

Follow-up	Outcome	Intervention	Coeffecient	Standard error	SUCRA ranking
1 yr	VAS	mFX-II	0.139	0.296	MFX-III > MFX-II > MFX-I1
		mFX-III	0.023	0.457
	KOOS	mFX-II	-2.296	2.835	MFX-III > MFX-II > MFX-I1
		mFX-III	-2.296	5.775
	Lysholm score	mFX-II	-17.008	11.160	MFX-I > MFX-III > MFX-II3
		mFX-III	-5.660	4.427
	IKDC score	mFX-II	2.782	1.811	MFX-III > MFX-II > MFX-I1
		mFX-III	4.339	2.228
	Cincinnati score	mFX-II	4.257	4.543	MFX-II > MFX-I1
	MRI filling	mFX-II	0.383	0.312	MFX-III > MFX-II > MFX-I1
		mFX-III	1.860	1.770
	MOCART score	mFX-II	11.950	7.419	MFX-III > MFX-II > MFX-I1
		mFX-III	30.700	14.168
	Adverse events	mFX-II	-0.529	0.373	MFX-III > MFX-II > MFX-I1
		mFX-III	-0.138	0.546
	Failure events	mFX-II	-0.520	0.777	MFX-II > MFX-I1
2 yr	VAS	mFX-II	0.377	0.452	MFX-III > MFX-II > MFX-I1
		mFX-III	0.690	0.795
	KOOS	mFX-II	1.899	2.971	MFX-II > MFX-I1
	Lysholm score	mFX-II	0.550	6.952	MFX-II > MFX-I > MFX-III3
		mFX-III	-19.560	9.814
	IKDC score	mFX-II	4.548	4.545	MFX-III > MFX-II > MFX-I1
		mFX-III	7.947	9.405
	Cincinnati score	mFX-II	-6.227	3.775	MFX-II = MFX-I2
	MRI filling	mFX-II	0.840	0.468	MFX-II > MFX-III > MFX-I3
		mFX-III	0.418	0.508
	MOCART	mFX-III	10.600	9.281	MFX-III > MFX-I1
5 yr	VAS	mFX-III	1.900	1.917	MFX-III > MFX-I1
	IKDC score	mFX-III	3.000	2.121	MFX-III > MFX-I1

¹Newer generations better than older generations.

²Newer generations equal to older generations.

³Newer generations worse than older generations.

VAS: Visual Analog Scale; mFX: Microfracture; KOOS: Knee Osteoarthritis Outcome Scale; IKDC: International Knee Documentation Committee; MRI: Magnetic resonance imaging; MOCART: Magnetic resonance observation of cartilage repair tissue.

Table 3 Risk of bias for all the pairwise comparisons for functional outcome from the network assessed with Cochrane’s Confidence in network meta-analysis approach

Comparison	Number of studies	Within-study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence rating	Reasons for downgrading
MFx-I: MFx-II	7	Some concerns	Some concerns	No concerns	Major concerns	Some concerns	No concerns	Moderate	Imprecision in results
MFx-I: MFx -III	1	Some concerns	Some concerns	No concerns	Major concerns	Some concerns	No concerns	Moderate	Imprecision in results
MFx-II: MFx -III	1	Some concerns	Some concerns	No concerns	Major concerns	Some concerns	No concerns	Moderate	Imprecision in results

MFx: Microfracture.