Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials

Gao, Han; Liu, Song; Qin, Shanshan; Yang, Jiali; Yue, Tian; Ye, Bengui; Tang, Yue; Feng, Jie; Hou, Jun; Danzeng, Dunzhu

doi:10.1186/s12872-024-03742-0

Table 1 Characteristics of included studies

From: Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials

	Reference (study, year)	Animal	Total N	Age	Weight(SD)	Follow-up	Timing of Treatment (post-MI)	Baseline EF or FS (post-MI)	Encapsulation materials	Hydrogel	Funding Source	Setting
Rufaihah et al. 2013 [18]	Combined group	Rats	7F	Not reported	250 g	4w	0	Not reported	VEGF-A	PEGylated fibrinogen hydrogel	Agency	Singapore
Rufaihah et al. 2013 [18]	Hydrogel group		7F
Rufaihah et al. 2017 [19]	Combined group	Rats	10 M	Not reported	250-300 g	4w	0	Not reported	VEGF+ANG-1	polyethylene glycol-fibrinogen (PF) hydrogels	Agency/Idustry	China
Rufaihah et al. 2017 [19]	Hydrogel group		10 M
Rocker et al. 2022 [20]	Combined group	Mice	4	Not reported	24–28 g	4w	0	Not reported	VEGF+IL-10 + PDGF	S-GC-PNIPAM hydrogel	Agency	USA
Rocker et al. 2022 [20]	Hydrogel group		4
Steele et al. 2017 [21]	Combined group	Rats	10 M	Not reported	250–300 g	4w	0	Not reported	HGFdf	PEG-PNIPAM-P1 hydrogel	Agency	USA
Steele et al. 2017 [21]	Hydrogel group		10 M
Steele et al. 2020 [22]	Combined group	Rats	12 M	Not reported	250-300 g	4w	0	Not reported	HGFdf+ESA 1α	hydhyaluronic acid poly(ethyleneglycol) poly(lactic acid) hydrogel	Agency	USA
Steele et al. 2020 [22]	Hydrogel group		12 M
Steele et al. 2020 [22]	Combined group	Sheep	7 M	Not reported		8w	0	Not reported	HGFdf+ESA 1α	hydhyaluronic acid poly(ethyleneglycol) poly(lactic acid) hydrogel	Agency	USA
Steele et al. 2020 [22]	Hydrogel group		7 M
Chow et al. 2017 [23]	Combined group	Rats	5 M	8 weeks		10w	0	EF = 45.4 ± 7.8	Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte	PEG hydrogel	Agency/Idustry	UK
Chow et al. 2017 [23]	Hydrogel group		6 M
Gaffey et al. 2015 [24]	Combined group	Rats	10 M	Not reported	250-300 g	4w	0	Not reported	Rat bone marrow-derived endothelial progenitor cells	hyaluronic acid hydrogel		USA
Gaffey et al. 2015 [24]	Hydrogel group		10 M
Hakravarti et al. 2018 [25]	Combined group	Mice	4F	12 weeks		3w	0	Not reported	Human adipose-derived stem cells	gelatin methacrylamide (GelMA)	Agency	USA
Hakravarti et al. 2018 [25]	Hydrogel group		4F
Paul et al. 2014 [26]	Combined group	Rats	7 M	Not reported	200-250 g	2w	0	EF = 36.6	Graphene oxide +VEGF	GelMA hydrogel	Agency/Idustry	USA
Paul et al. 2014 [26]	Hydrogel group		7 M
Qian et al. 2022 [27]	Combined group	Rats	8 M	Not reported	Not reported	4w	0w	Not reported	platelet concentrates including PRP	ALG-HA hydrogels	Agency/Idustry	China
Qian et al. 2022 [27]	Hydrogel group		8 M
Xu et al. 2017 [28]	Combined group	Rats	6 M	Not reported	225-250 g	4w	1w	Not reported	rat bone-marrow mesenchymal stem cells	chitosan hydrogel	Agency	China
Xu et al. 2017 [28]	Hydrogel group		6 M
Follin et al. 2018 [29]	Combined group	Rats	13 M	Not reported	266 ± 15 g	4w	0w	EF = 45.04 ± 9.08	adipose-derived Mesenchymal stem cell	Alginate Hydrogel	Agency	Denmark
Follin et al. 2018 [29]	Hydrogel group		10 M
Fu et al. 2022 [30]	Combined group	Rats	10 M	8 weeks	200–250 g	4w	0w		bFGF	CMCS-S-S-Py and rBSA hydrogel	Agency/Idustry	China
Fu et al. 2022 [30]	Hydrogel group		10 M
Purcell et al. 2018 [31]	Combined group	Pigs	7 M	Not reported	20,000 g	4w	0w	Not reported	rTIMP-3	hyaluronic acid (HA)-based hydrogel	Agency	USA
Purcell et al. 2018 [31]	Hydrogel group		7 M
Purcell et al. 2014 [32]	Combined group	Pigs	7 M	Not reported	25,000 g	4w	0w	Not reported	rTIMP-3	Dextran sulphate (DS) / ALD modification of its diol groups hydrogels	Agency/Idustry	USA
Purcell et al. 2014 [32]	Hydrogel group		7 M
Cimenci et al. 2022 [33]	Combined group	Mice	7F	Not reported	Not reported	5w	0w	Not reported	fisetin	thermoresponsive collagen hydrogel	Agency/Idustry	Canada
Cimenci et al. 2022 [33]	Hydrogel group		7F
Fan et al. 2019 [34]	Combined group	Rats	12F	Not reported	200-220 g	4w	0w	Not reported	GST-TIMP-bFGF	collagen-GSH hydrogel	Agency/Idustry	China
Fan et al. 2019 [34]	Hydrogel group		12F
Chen et al. 2018 [35]	Combined group	Rats	11 M	Not reported	350-375 g	5w	0w	Not reported	EPCs EVs	adamantane-modified HA (Ad-HA) and β-cyclodextrin-modified HA (CD-HA) shear-thinning hydrogel (STG)	Agency/Idustry	USA
Chen et al. 2018 [35]	Hydrogel group		10 M
Kim et al. 2020 [36]	Combined group	Mice	9 M	7 weeks	20-22 g	4w	0w	Not reported	MSC	gelatin–hydroxyphenyl propionic acid (GH) hydrogels	Agency	Korea
Kim et al. 2020 [36]	Hydrogel group		9 M
Han et al. 2019 [36]	Combined group	Rats	5 M			4w	0w	Not reported	UMSC exosomes	(PA-GHRPS and NapFF) PGN hydrogel	Agency/Idustry	China
Han et al. 2019 [36]	Hydrogel group		5 M
Chen et al. 2013 [37]	Combined group	Rats	8 M	6 weeks	200-250 g	4w	0w	EF = 37.9	allogeneic bone marrow mononuclear cells	hyaluronan (HA) hydrogel	Agency/Idustry	Taiwan of China
Chen et al. 2013 [37]	Hydrogel group		8 M
Chen et al. 2014 [38]	Combined group	Pigs	7	Not reported	Not reported	8w	0w	EF = 45.8	bone marrow mononuclear cells	hyaluronan (HA) hydrogel	Agency/Idustry	Taiwan of China
Chen et al. 2014 [38]	Hydrogel group		8
Projahn et al. 2014 [39]	Combined group	Mice	8 M	Not reported	25–26 g	4w	0w	Not reported	CXCL12 (S4V)、Met-CCL5	sP(EO-stat-PO)/oxidation of thiolated (FDH) / PEG-diacrylate(SDH)	Agency/Idustry	Germany
Projahn et al. 2014 [39]	Hydrogel group		8 M
Mathieu et al. 2012 [40]	Combined group	Rats	9F	Not reported	180-190 g	8w	0w	Not reported	rat bone-marrow mesenchymal stem cells	Silanized-Hydroxypropyl Methyicellulose hydrogel	Agency/Idustry	France
Mathieu et al. 2012 [40]	Hydrogel group		7F
Xu et al. 2014 [41]	Combined group	Rats	5F	Not reported	150-200 g	4w	0w	Not reported	Rat bone marrow mesenchymal stem cells	Col-SH/OAC-PEG-OAC hybrid hydrogels	Agency/Idustry	China
Xu et al. 2014 [41]	Hydrogel group		5F
Chen et al. 2017 [42]	Combined group	Mice	6 M	8-11 weeks		2w	0w	Not reported	Curcumin+NO	FFE-ss-ERGD hydrogels	Agency/Idustry	China
Chen et al. 2017 [42]	Hydrogel group		6 M
Awada et al. 2017 [43]	Combined group	Rats	8 M	6-7 weeks	175-225 g	8w	0w	Not reported	TIMP-3 + FGF-2+ SDF-1α	fibrin gel hydrogels	Agency	USA
Awada et al. 2017 [43]	Hydrogel group		8 M
Wang et al. 2010 [44]	Combined group	Rats	8F	6 weeks		4w	0w	Not reported	bFGF	chitosan hydrogel	Agency/Idustry	China
Wang et al. 2010 [44]	Hydrogel group		8F
Wang et al. 2012 [45]	Combined group	Rats	32F	6 weeks		4w	1w	Not reported	mouse embryonic stem cells	OPF hydrogels [fumaryl chloride and poly(ethylene glycol) (PEG)]	Agency	USA
Wang et al. 2012 [45]	Hydrogel group		24F
Wang et al. 2014 [46]	Combined group	Rats	20 M	Not reported	250 ± 10 g	4w	0w	Not reported	CD29 Rat brown adipose-derived stem cells	chitosan hydrogel	Agency/Idustry	China
Wang et al. 2014 [46]	Hydrogel group		20 M
Ding et al. 2020 [47]	Combined group	Rats	6 M	Not reported	250 g	4w	0w	EF = 42.4 FS = 21.9	mesenchymal stem cells	methacrylate hyaluronic acid hydrogel	Agency/Idustry	China
Ding et al. 2020 [47]	Hydrogel group		6 M
Li et al. 2018 [48]	Combined group	Mice	4 M	8–10 weeks	20 ± 5 g	4w	0w	Not reported	Mouse Induced pluripotent stem (MiPS) cells	folic acid (FA) Hydrogel	Agency/Idustry	China
Li et al. 2018 [48]	Hydrogel group		4 M
Zhu et al. 2017 [49]	Combined group	Rats	7 M	8-10 weeks	200-250 g	4w	0w	Not reported	bFGF	Dex-PCL-HEMA/PNIPAAm hydrogel	Agency/Idustry	China
Zhu et al. 2017 [49]	Hydrogel group		7 M
Cohen et al. 2014 [50]	Combined group	Mice	5 M	10 weeks	25-30 g	2w	0w	Not reported	Neuregulin-1β	hyaluronate hydrogel	Agency	USA
Cohen et al. 2014 [50]	Hydrogel group		5 M
Cohen et al. 2020 [22]	Combined group	Sheep	6 M	26-30 weeks	35,000-40,000 g	8w	0w	Not reported	Neuregulin-1β	hyaluronate hydrogel	Agency	USA
Cohen et al. 2020 [22]	Hydrogel group		4 M
Ding et al. 2020 [51]	Combined group	Rats	5 M	8 weeks	200-250 g	4w	0w	Not reported	catalase + hyperbranched polymers	Reactive Oxygen Species Scavenging and O2 Generating Injectable Hydrogel/hyaluronic acid (HA-MA)	Agency/Idustry	China
Ding et al. 2020 [51]	Hydrogel group		5 M
Zhou et al. 2021 [52]	Combined group	Rats	10 M	Not reported	250 ± 10 g	4w	0w	Not reported	melanin	Alginate (Alg) hydrogels	Agency/Idustry	China
Zhou et al. 2021 [52]	Hydrogel group		10 M
Chen et al. 2021 [53]	Combined group	Rats	4 M	6-8 weeks	220-250 g	4w	0w	Not reported	Astragaloside IV	(PEGDA-PBA) - (HA-SH) hydrogel	Agency/Idustry	China
Chen et al. 2021 [53]	Hydrogel group		4 M
Chen et al. 2014 [54]	Combined group	Rabbits	7 M	Not reported	2200-2600 g	4w	1w	EF = 56.13 ± 7.51	Rabbit bone marrow stem cells	α-cylcodextrin/MPEG–PCL–MPEG hydrogel	Idustry	China
Chen et al. 2014 [54]	Hydrogel group		7 M
Wu et al. 2011 [55]	Combined group	Rats	10	Not reported	200-250 g	5w	1w	FS = 28.9	VEGF	PVL-b-PEG-b-PVL/aliphatic polyester hydrogel (HG)	Agency/Idustry	Canada
Wu et al. 2011 [55]	Hydrogel group		11
Khan et al. 2022 [56]	Combined group	Rats	9F	Not reported	250-300 g	4w	0w	Not reported	hAMSC/amniotic stromal mesenchymal stem cells	chitosan and hyaluronic acid (C/HA) based hydrogel	Agency	Canada
Khan et al. 2022 [56]	Hydrogel group		10F
Cheng et al. 2012 [57]	Combined group	Mice	8 M	10-12 weeks	Not reported	3w	0w	EF = 31.8	Cardiosphere-derived cells (CDCs)	hyaluronan and porcine gelatin hydrogel	Agency	USA
Cheng et al. 2012 [57]	Hydrogel group		8 M
Zhu et al. 2022 [58]	Combined group	Rats	6 M	Not reported	200 g	4w	0w	Not reported	Mesenchymal stem cell and 68Ga3+ cations	GNR@SNs/PLGA-PEG-PLGA hydrogel	Agency/Idustry	China
Zhu et al. 2022 [58]	Hydrogel group		6 M
Wu et al. 2023 [59]	Combined group	Mice	6 M	8 weeks	22-25 g	4w	0w	EF = 37.55 FS = 19	SDF-1/CMs	dECM hydrogel	Agency/Idustry	China
Wu et al. 2023 [59]	Hydrogel group		6 M
Montazeri et al. 2020 [60]	Combined group	Rats	5 M	8 weeks	250–300 g	4w	0w	Not reported	vascular endothelial growth factor (VEGF)/ hESC-CPC-derived cardiomyocytes	fibrin hydrogel	Agency/Idustry	Iran
Montazeri et al. 2020 [60]	Hydrogel group		5 M
Reis et al. 2015 [61]	Combined group	Rats	7 M	Not reported	200–250 g	6w	0w	Not reported	prosurvival angiopoietin-1–derived peptide, QHREDGS	chitosan-collagen hydrogel	Agency/Idustry	Canada
Reis et al. 2015 [61]	Hydrogel group		7 M
Liu et al. 2020 [62]	Combined group	Mice	8	Not reported	Not reported	4w	0w	Not reported	bone marrow-derived Mesenchymal stem cell	chitosan (CS) thermosensitive hydrogel	Agency/Idustry	China
Liu et al. 2020 [62]	Hydrogel group		8
Vong et al. 2018 [63]	Combined group	Mice	6 M	7-8 weeks	32–35 g	4w	0w	Not reported	NO	PMNT-PEG-PMNT PArg-PEG-PArg+PAAc	Agency/Idustry	Japan
Vong et al. 2018 [63]	Hydrogel group		6 M
Gao et al. 2020 [64]	Combined group	Mice	5 M	8-10 weeks	Not reported	4w	0w	Not reported	Mesenchymal stem cells	bioglass (BG)/γ-polyglutamic acid/chitosan hydrogel	Agency/Idustry	China
Gao et al. 2020 [64]	Hydrogel group		5 M
Ciuffreda et al. 2018 [65]	Combined group	Rats	10F	Not reported	Not reported	4w	1w	EF25.14 ± 4.15 FS30.90 ± 4.68	rat bone-marrow MSC	polyethylene glycol (PEG)-based hydrogel containing heparin (H-HG)	Agency	Italy
Ciuffreda et al. 2018 [65]	Hydrogel group		10F
Chang et al. 2016 [66]	Combined group	Pigs	6 M	20 weeks	22.26 ± 0.78 kg	8w	0w	EF = 47.5	human cord blood mononuclear cells	hyaluronan (HA) hydrogel	Agency/Idustry	Taiwan of China
Chang et al. 2016 [66]	Hydrogel group		6 M
Chen et al. 2019 [67]	Combined group	Rats	10 M	Not reported	Not reported	4w	0w	Not reported	IL-10	AdHA and CDHA hydrogel	Agency/Idustry	USA
Chen et al. 2019 [67]	Hydrogel group		8 M
Song et al. 2014 [68]	Combined group	Rats	10 M	6 weeks	Not reported	4w	0w	Not reported	stem cell homing factor (SDF-1) angiogenic peptides	Biomimetic hyaluronic acid based hydrogel	Agency	Korea
Song et al. 2014 [68]	Hydrogel group		10 M
Qi et al. 2020 [69]	Combined group	Rats	8 M	Not reported	200-250 g	4w	1w	Not reported	Bioglass	Alginate hydrogel	Agency/Idustry	China
Qi et al. 2020 [69]	Hydrogel group		8 M
Bao et al. 2017 [70]	Combined group	Rats	13 M	Not reported	250 ± 20 g	4w	0w	Not reported	adipose tissue-derived stromal cells	PEG-MEL/HA-SH/GO hydrogels	Agency/Idustry	China
Bao et al. 2017 [70]	Hydrogel group		13 M
Firoozi et al. 2020 [71]	Combined group	Rats	6 M	Not reported	280-350 g	4w	0w	Not reported	human bone marrow-derived mesenchymal stem cells	(RADA)4-SDKP hydrogel	Agency/Idustry	Iran
Firoozi et al. 2020 [71]	Hydrogel group		6 M
Shafei et al. 2022 [72]	Combined group	Rats	6 M	12 weeks	250-280 g	4w	0w	FS = 30	microRNA-126/146a mimics in exosomes	alginate hydrogel	Agency	USA
Shafei et al. 2022 [72]	Hydrogel group		6 M
Lü et al. 2010 [73]	Combined group	Rats	10 M	6 weeks	Not reported	4w	1w	Not reported	nuclear-transferred embryonic stem cells	temperature-responsive chitosan hydrogel	Agency/Idustry	China
Lü et al. 2010 [73]	Hydrogel group		10 M
Zhu et al. 2022 [58]	Combined group	Rats	10 M	6 weeks	Not reported	4w	0w	Not reported	Umbilical cord mesenchymal stem cells	GelMA-O5/rGO hydrogels	Agency/Idustry	China
Zhu et al. 2022 [58]	Hydrogel group		10 M
Bao et al. 2023 [74]	Combined group	Rats	5 M	Not reported	200-220 g	4w	1w	Not reported	superparamagnetic iron oxide (SPIO)	chitosan/β-glycerophosphate (CS/GP) hydrogel	Agency/Idustry	China
Bao et al. 2023 [74]	Hydrogel group		5 M
Wang et al. 2009 [75]	Combined group	Rats	12 M	Not reported	200–250 g	4w	0w	Not reported	recombined human erythropoietin	α-cyclodextrin/MPEG–PCL–MPEG hydrogel	Agency	China
Wang et al. 2009 [75]	Hydrogel group		12 M
Wang et al. 2009 [76]	Combined group	Rabbits	8 M	Not reported	2200–2600 g	4w	0w	Not reported	Bone marrow stem cells	α-cyclodextrin/MPEG–PCL–MPEG hydrogel	Agency/Idustry	China
Wang et al. 2009 [76]	Hydrogel group		8 M
Vu et al. 2015 [77]	Combined group	Pigs	6 M	Not reported	65,000-70,000 g	8w	0w	Not reported	PRP, allopurinol, ascorbic acid and ibuprofen	Gelatin hydrogel	Agency	Singapore
Vu et al. 2015 [77]	Hydrogel group		6 M
Kraehenbuehl et al. 2011 [78]	Combined group	Rats	8 M	Not reported	200-250 g	6w	0w	EF = 52.7	hESC-derived ELC + SMLC+Tβ4	PEG-hydrogels	Agency/Idustry	USA
Kraehenbuehl et al. 2011 [78]	Hydrogel group		8 M
Wan et al. 2014 [79]	Combined group	Rats	14 M	Not reported	200-250 g	4w	0w	Not reported	short-hairpin RNA of angiotensin	(Dex-PCL-HEMA/PNIPAAm) hydrogel	Agency/Idustry	China
Wan et al. 2014 [79]	Hydrogel group		14 M
Wang et al. 2018 [80]	Combined group	Rats	17 M	Not reported	250 ± 20 g	6w	0w	Not reported	plasmid DNA-eNOs + ADSCs	TA-PEG/HA-SH hydrogels	Agency/Idustry	China
Wang et al. 2018 [80]	Hydrogel group		16 M
Lu et al. 2009 [81]	Combined group	Rats	12F	Not reported	Not reported	4w	1w	Not reported	Mouse embryonic stem cells	temperature-responsive chitosan hydrogel	Agency/Idustry	China
Lu et al. 2009 [81]	Hydrogel group		13F
Li et al. 2014 [82]	Combined group	Rats	6 M	Not reported	250 ± 20 g	4w	0w	Not reported	Rat brown adipose-derived stem cells	SWCNTs-modified PNIPAAm hydrogel	Agency/Idustry	China
Li et al. 2014 [82]	Hydrogel group		6 M
Li et al. 2010 [83]	Combined group	Rabbits	11 M	Not reported	2000–2500 g	4w	1w	Not reported	bone marrow-derived mononuclear cells	Dex-PCL-HEMA/PNIPAAm hydrogel	Agency/Idustry	China
Li et al. 2010 [83]	Hydrogel group		8 M
Hu et al. 2022 [84]	Combined group	Mice	5 M	8-10 weeks		4w	0w	Not reported	ISL1-Mesenchymal stem cell-Exo	angiogenin-1 hydrogel (Ang-1 gel)	Agency/Idustry	China
Hu et al. 2022 [84]	Hydrogel group		5 M
Li et al. 2021 [85]	Combined group	Pigs	6 M	Not reported	45,000-50,000 g	4w	0w	EF = 35	MSN / miR-21-5p	gelatin hydrogels	Agency/Idustry	China
Li et al. 2021 [85]	Hydrogel group		6 M
Liu et al. 2021 [86]	Combined group	Rats	20 M	6-8 weeks	200 ± 10 g	4w	0w	Not reported	puerarin + rBMesenchymal stem cell	hyaluronic acid (HA-Tyr) hydrogel	Agency/Idustry	China
Liu et al. 2021 [86]	Hydrogel group		20 M
Wu et al. 2021 [87]	Combined group	Mice	15 M	8 weeks	22-25 g	4w	0w	Not reported	VEGF and B/SF microspheres	alginate based composite hydrogel	Agency/Idustry	China
Wu et al. 2021 [87]	Hydrogel group		15 M
Chen et al. 2020 [88]	Combined group	Mice	20 M	8-12 weeks		4w	0w	EF = 36.4	Rat adipose-derived mesenchymal stem cells	Col-Transglutaminase cross-linked gelatin	Agency/Idustry	China
Chen et al. 2020 [88]	Hydrogel group		20 M
Zhang et al. 2021 [89]	Combined group	Mice	5 M		22-28 g	4w	0w	Not reported	Dendritic cell-derived exosomes (DEXs)	Alginate hydrogel	Agency/Idustry	China
Zhang et al. 2021 [89]	Hydrogel group		5 M
Chen et al. 2020 [90]	Combined group	Mice	13 M	6 weeks		4w	0w	Not reported	colchicine	(PLGA–PEG–PLGA) hydrogel	Agency/Idustry	China
Chen et al. 2020 [90]	Hydrogel group		11 M
Xia et al. 2015 [91]	Combined group	Mice	8F	Not reported	Not reported	4w	0w	Not reported	Mouse bone marrow mesenchymal stem cells	poly(NIPAAm-co-HEMA-co-HEMAPCL)-type I collagen hydrogel	Agency	China
Xia et al. 2015 [91]	Hydrogel group		8F
	Lyu et al. 2020
	Combined group	Rats	5 M	Not reported	220 ± 20 g	4w	0w	Not reported	MSC aggregates (FMAs) hMesenchymal stem cell+PLGA	OHA@HHA hydrogel	Agency/Idustry	China
	Hydrogel group		5 M
Sakakibara et al. 2002 [92]	Combined group	Rats	10 M	Not reported	250-290 g	4w	1w	FS = 19.8 ± 4.1	bFGF+ fetal cardiomyocyte	gelatin hydrogels	Agency	Japan
Sakakibara et al. 2002 [92]	Hydrogel group
Zheng et al. 2022 [93]	Combined group	Rats	3 M	Not reported	250 ± 20 g	4w	0w	Not reported	bone mesenchymal stem cells (BMesenchymal stem cell)/KLT (a VEGF mimetic peptide with pro-angiogenic effects)	MaHA/B-G-SH/Fe3+ hydrogels	Agency/Idustry	China
Zheng et al. 2022 [93]	Hydrogel group		3 M
Zheng et al. 2022 [94]	Combined group	Rats	3 M	Not reported	250 ± 20 g	4w	0w	Not reported	S1P SS-31(plasma enzyme-degradable peptide)/Lipo	PAMB-G-TK/4-Arm-PEG-SG Hydrogels	Agency/Idustry	China
Zheng et al. 2022 [94]	Hydrogel group		3 M
Liu et al. 2012 [95]	Combined group	Rats	22 M	Not reported	Not reported	4w	0w	Not reported	Rat adipose-derived mesenchymal stem cells	chitosan hydrogel	Agency/Idustry	China
Liu et al. 2012 [95]	Hydrogel group
Yuan et al. 2019 [96]	Combined group	Rats	8 M	9–10 weeks	200 ± 20 g	4w	0w	Not reported	Mydgf	citrate-containing polyester hydrogel (PPC-ET/PEG Hydrogels)	Agency/Idustry	China
Yuan et al. 2019 [96]	Hydrogel group

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