Table 3.

Studies of two-step and one-step procedures for ankle scaffold-based repair

Procedure	Product	Scientific publication	Type of study	LOE	No. of patients	Lesion size (cm2)	Follow-up (mo)	Results
Two-step
MACT	MACI	Schneider et al[6], 2009	Case series	IV	20	2.3	21	Significant improvement in functional score
								Pain improved in 70% of patients
		Giza et al[5], 2010	Case series	IV	10	1.3	24	Significant clinical improvement at 1 yr and maintained at 2 yr
		Aurich et al[16], 2011	Case series	IV	18	-	25	Significant improvement in all clinical scores 64% were excellent or good Age and symptoms duration were correlated with results
		Dixon et al[17], 2011	Case series	IV	25	1.3	44	72% improved symptoms 78% patients over 40 yr reported restricted recreational activity
		Lee et al[18], 2013	Case series	IV	38	1.9	24	Functional outcomes improved significantly at 2 yr 68% were excellent or good outcome 75% ICRS grade I or II in 2nd look arthroscopy at 1 yr
		Johnson et al[19], 2013	Case series	IV	18	1.9	82	Functional outcomes improved at final follow-up
		Giannini et al[20], 2014	Case series	IV	46	1.6	87	Significant clinical improvement at 1 yr and maintained at 3 yr; 3 failures
	Hyalograft C	Giannini et al[21], 2008	Case series	IV	46	1.6	36	Significant clinical improvement at 1 yr and 3 yr Results correlated with age and previous surgery Hyaline-like cartilage regeneration in histological evaluation
		Battaglia et al[22], 2011	Case series	IV	20	2.7	60	Significant clinical improvement T2 mapping MRI showed 69% of lesion are covered with repair tissue
		Nehrer et al[23], 2011	Case series	IV	13	-	47	Significant clinical improvement in all cases
		Domayer et al[24], 2012	Comparative study	III	18	1.2	65	Significant clinical improvement but no significant difference compared to MFX group No difference between MFX and MACT on T2 maps
		Apprich et al[25], 2012	Case series	IV	10	1.2	48	Significant clinical improvement No differences in functional outcome and MOCART score between MFX and MACT
Two-step
BMDCT	Spontostan Powder HYAFF-11	Giannini et al[8], 2009	Case series	IV	48 (25 HA membrane, 23 collagen powder)	2.1	29	Significant clinical improvement at 1 yr maintained at 2 yr Similar results with two scaffolds Correlation between clinical outcome and lesion size
	Spontostan Powder HYAFF-11	Giannini et al[26], 2010	Comparative study	III	25 BMDCT 46 two-step MACI	2.2 1.6	39 57	Significant clinical improvement at 1 yr and further improvement at 3 yr 76% complete intergration with surrounding cartilage on MRI Hyaline-like cartilage tissue on histological evaluation
	HYAFF-11	Battaglia et al[27], 2011	Case series	IV	20	1.5	24	85% excellent or good clinical results at 2 yr 78% of lesion are covered with repair tissue comparable to hyaline cartilage
	Spontostan Powder HYAFF-11	Giannini et al[28], 2013	Case series	IV	49	2.1	29	Significant clinical improvement at 1 yr with subsequent significant decrease at 2 and 3 yr 78% of repaired tissue similar to hyaline cartilage on T2 maps
	Spongostan Powder	Buda et al[29], 2014	Case series	IV	64	5.3	53	Clinical results peaked at 2 yr, declining gradually at follow-up of 6 yr
	Biopad	Cadossi et al[30], 2014	Comparative study	III	15 BMDCT 15 BMDCT with PEMF	2 1.9	12 12	Significant clinical improvement in both groups
	HYAFF-11	Buda et al[4], 2015	Case series	IV	40	1.8	48	Significant clinical improvement Higher presence of hyaline-like cartilage in BMDCT than ACI on MRI T2 mapping
	HYAFF-11 Spongostan Powder Biopad	Vannini et al[31], 2017	Case series	IV	140	2	26	Significant clinical improvement at 2 yr maintained at 4 yr Return to sports at preinjury level; 32.1% at 12 mo, 72.8% at 48 mo
AMIC	Unclear	Wiewiorski et al[7], 2013	Case series	IV	23	-	23	Significant clinical improvement
	Chondro-Gide	Valderrabano et al[32], 2013	Case series	IV	26	-	31	Significant clinical improvement Normal signal intensity of repair tissue was seen in 15% on MRI
	Chondro-Gide	Kubosch et al[33], 2016	Case series	IV	17	2.4	39	Significant clinical improvement MOCART score correlated with AOFAS score
	Chondro-Gide	Wiewiorski et al[34], 2016	Case series	IV	60	-	47	Calcaneal osteotomy was performed in 63% of patients Low rate for return to sports; postoperative sports activity levels remain stable when compared with preoperative levels
Cartilage ECM	BioCartilage	Desai S[35], 2016	Case series	IV	9	1.3	12	78% excellent, 22% good clinical outcomes
		Clanton et al[36], 2014	Case series	IV	7	-	8	Significant clinical improvement
ACIC	Cartifill	Volpi P et al[37], 2014	Case series	IV	5	3.1	6	Significant clinical improvement at 6 mo
Cell-free scaffold	MaioRegen®	Christensen et al[38], 2015	Case series	IV	4	-	30	No clinical scores improvement No improvement in MOCART score and 3 patients had 0%-10% bone formation in defect at 1 yr on CT