Scaffolds based therapy for osteochondral lesions of the talus: A systematic review

Table 1 Inclusion and exclusion criteria

Inclusion criteria
	Therapeutic clinical studies evaluating the effect of scaffolds for ankle cartilage repair
	All patients included had > 6-mo follow-up
	Published in a peer-reviewed journal
	Published in English
	Full-text version available
Exclusion criteria
	Review articles
	Case reports
	Technique articles
	Cadaveric studies
	Animal studies
	In vivo studies

Table 2 Modified Coleman Methodology Score

		Score
Part A: Only 1 score to be given for each section
Number of study patients
	> 60	10
	41-60	7
	20-40	4
	< 20, not stated	0
Mean follow-up (mo)
	> 24	5
	12-24	2
	< 12, not stated or unclear	0
Number of different surgical procedures included in each reported outcome
	1	10
	> 1, but > 90% of patients undergoing the 1 procedure	7
	Not stated, unclear, or < 90% of subjects undergoing the 1 procedure	0
Type of study
	Randomized controlled trial	15
	Prospective cohort study	10
	Retrospective cohort study	0
Diagnostic certainty (MRI)
	In all	5
	In > 80%	3
	In < 80%	0
Description of surgical procedure given
	Adequate (technique stated and necessary details of that type of procedure provided)	5
	Fair (technique only stated without elaboration)	3
	Inadequate, not stated, or unclear	0
Description of postoperative rehabilitation
	Well described (ROM, WB, and sport)	10
	Not adequately described (2 items between ROM, WB, and sport)	5
	Protocol not reported	0
Part B: Scores may be given for each option in each of the 3 sections if applicable
Outcome criteria
	Outcome measures clearly defined	2
	Timing of outcome assessment clearly stated (e.g., at best outcome after surgery or follow-up)	2
	Objective, subjective, and imaging criteria	6
	2 items between objective, subjective, and imaging criteria	4
	Objective, subjective, or radiological criteria	2
Procedure for assessing outcomes
	Patients recruited (results not taken from surgeons' files)	5
	Investigator independent of surgeon	4
	Written assessment	3
	Completion of assessment by patinets themselves with minimal investigator assistance	3
Description of patient selection process
	Selection criteria reported and unbiased	5
	Recruitment rate reported
	> 80%	5
	< 80%	3
	Eligible patients not included in study satisfactorily accounted for or 100% recruitment	5

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

Table 4 Patient demographics and clinical characteristics

	Procedure
	Total	MACT	BMDCT	AMIC	Cartilage ECM	ACIC	Cell-free scaffold
Treatment groups, n	30	13	9	4	2	1	1
Ankles, n	897	330	416	126	16	5	4
Sex, male/female/unknown, n	501/322/72	174/111/45	238/153/22	79/47/0	7/9/0	3/2/0	-
Age, yr, weighted mean (range)	30.9 (19-61)	30.1	30.2	34.9	42.7	25.6	-
Duration of symptoms, mo, weighted mean (range)	34.3 (6-216)	34.5	36.5	23	-	-	-
Lesion size, mm2, weighted mean (range)	215 (116-527)	171	248	240	130	-	-
Follow-up, mo, weighted mean (range)	37.7 (6-87)	45.8	32.7	38.2	10.4	6	30

Table 5 Level and quality of evidence of included studies n (%)

		Total Studies	Procedure groups
			MACT	BMDCT	AMIC	Cartilage ECM	ACIC	Cell-free scaffold
Level of evidence
	1	0	0	0	0	0	0	0
	2	1 (3.6)	0	2 (22.2)	0	0	0	0
	3	3 (10.7)	2 (15.4)	2 (22.2)	0	0	0	0
	4	24 (85.7)	11 (84.6)	5 (55.6)	4 (100)	2 (100)	1 (100)	1 (100)
Quality of evidence
	Excellent (MCMS ≥ 85)	0	0	0	0	0	0	0
	Good (MCMS 70-84)	0	0	0	0	0	0	0
	Fair (MCMS 55-69)	7 (25.0)	3 (23.1)	4 (44.4)	0	0	0	0
	Poor (MCMS < 55)	21 (75.0)	10 (76.9)	5 (55.6)	4 (100)	2 (100)	1 (100)	1 (100)

Table 6 Data reported (in percentage)

			Procedure
		Total	MACT	BMDCT	AMIC	Cartilage ECM	ACIC	Cell-free scaffold
Procedure groups, n		30	13	9	4	2	1	1
Demographic information		93	92	94	100	100	100	0
	Sex	90	85	89	100	100	100	0
	Mean age + range	97	100	100	100	100	100	0
Patient history		30	35	31	44	13	0	0
	Body mass index	33	31	33	50	50	0	0
	Mean duration of symptoms	23	38	22	25	0	0	0
	Previous traumatic experience(s)	33	38	44	50	0	0	0
	Activities of daily living/athletic participation	30	31	22	50	0	0	0
Study design		73	71	78	72	56	63	38
	Type of study	50	23	56	25	0	0	100
	Number of patients	97	100	100	100	100	100	0
	Percentage of patients in follow-up	97	100	100	100	100	100	0
	Consecutive patients	23	23	22	50	0	0	0
	Follow-up time + range/standard deviation	100	100	100	100	100	100	100
	Method of lesion size measurement	43	54	44	50	0	0	0
	Lesion classification system utilized	77	77	100	50	50	100	0
	Surgical approach used to access lesion	97	92	100	100	100	100	100
Clinical variables		49	53	50	58	33	33	33
	Lesion size	93	100	100	75	50	100	100
	Lesion location	77	77	100	75	50	0	0
	Presence of cyst	13	23	0	25	50	0	0
	Associated pathology	13	23	0	25	0	0	0
	Concomitant procedures	20	15	22	50	0	0	0
	Description of rehabilitation	80	77	78	100	50	100	100
Imaging data		73	81	83	75	50	0	100
	Imaging used to identify lesion	80	92	89	75	50	0	100
	Imaging used at follow-up	67	69	78	75	50	0	100
Patient-reported outcomes		85	85	100	88	0	100	100
	Pain, function, and activity scale, pre-operative	80	77	100	75	0	100	100
	Pain, function, and activity scale, at follow-up	90	92	100	100	0	100	100

Table 7 Clinical outcome scores utilized in included studies n (%)

Score	Studies, total	Procedure group
		MACT	BMDCT	AMIC	Cartilage ECM	ACIC	Cell-free scaffold
AOFAS	25 (89)	12 (92)	9 (100)	4 (100)	0 (0)	1 (100)	1 (100)
VAS	7 (25)	1 (8)	2 (22)	4 (100)	0 (0)	1 (100)	0 (0)
Tegner activity score	3 (11)	1 (8)	0 (0)	1 (25)	0 (0)	0 (0)	1 (100)
SF-36	2 (7)	1 (8)	2 (22)	0 (0)	0 (0)	0 (0)	0 (0)
FFI	2 (7)	1 (8)	0 (0)	1 (25)	0 (0)	0 (0)	0 (0)
FADI	1 (4)	0 (0)	0 (0)	0 (0)	1 (50)	0 (0)	0 (0)
HSS	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
LEAS	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
AHS	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
AAOS	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
ARS	1 (4)	0 (0)	0 (0)	1 (25)	0 (0)	0 (0)	0 (0)
Halasi score	1 (4)	0 (0)	1 (11)	0 (0)	0 (0)	0 (0)	0 (0)
Mazur ankle score	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Cincinnati score	1 (4)	1 (8)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)

AAOS: American Academy of Orthopaedic Surgeons; AHS: Ankle-Hindfoot Score; AOFAS: American Orthopaedic Foot and Ankle Society; ARS: Activity Rating Scale; FADI: Foot and Ankle Disability Index; FFI: Foot Function Index; HSS: Hannover Scoring System; LEAS: University of California Lower Extremity Activity Scale; SF-36: Short Form-36 Health Survey; VAS: Visual analog scale.