• Virani S.S.
• et al.

Heart disease and stroke statistics—2020 update: a report from the American Heart Association.

Circulation. 2020; 141: e139-e596

• Tsintou M.
• et al.

Taking central nervous system regenerative therapies to the clinic: Curing rodents versus nonhuman primates versus humans.

Neural Regen. Res. 2020; 15: 425-437

• Bhasin A.
• et al.

Stem cell therapy: a clinical trial of stroke.

Clin. Neurol. Neurosurg. 2013; 115: 1003-1008

• Steinberg G.K.
• et al.

Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: A phase 1/2a study.

Stroke. 2016; 47: 1817-1824

• Savitz S.I.
• et al.

A phase 2 randomized, sham-controlled trial of internal carotid artery infusion of autologous bone marrow-derived ALD-401 cells in patients with recent stable ischemic stroke (RECOVER-stroke).

Circulation. 2019; 139: 192-205

• Krause M.
• et al.

Cell-based therapies for stroke: are we there yet?.

Front. Neurol. 2019; 10: 656

• Lindvall O.
• Kokaia Z.

Stem cells in human neurodegenerative disorders–time for clinical translation?.

J. Clin. Invest. 2010; 120: 29-40

• Gopalakrishnan A.
• et al.

Hydrogel scaffolds: towards restitution of ischemic stroke-injured brain.

Transl. Stroke Res. 2019; 10: 1-18

• Letko Khait N.
• et al.

Wielding the double-edged sword of inflammation: building biomaterial-based strategies for immunomodulation in ischemic stroke treatment.

Adv. Funct. Mater. 2021; 2010674: 1-32

• Mandal A.
• et al.

Hydrogels in the clinic.

Bioeng. Transl. Med. 2020; 5e10158

Early efficacy of intra-articular HYADD® 4 (Hymovis®) injections for symptomatic knee osteoarthritis.

Joints. 2017; 5: 79-84

• Migliore A.
• et al.

Efficacy of a single intra-articular HYMOVIS ONE injection for managing symptomatic hip osteoarthritis: a 12-month follow-up retrospective analysis of the ANTIAGE register data.

Orthop. Res. Rev. 2020; 12: 19-26

• Mann D.L.
• et al.

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure.

Eur. J. Heart Fail. 2016; 18: 314-325

• Traverse J.H.
• et al.

First-in-man study of a cardiac extracellular matrix hydrogel in early and late myocardial infarction patients.

JACC Basic Transl. Sci. 2019; 4: 659-669

• Steinberg G.K.
• et al.

Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study.

J. Neurosurg. 2019; 131: 1462-1472

• Kalladka D.
• et al.

Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study.

Lancet. 2016; 388: 787-796

• Muir K.W.
• et al.

Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2).

J. Neurol. Neurosurg. Psychiatry. 2020; 91: 396-401

• Nakagomi N.
• et al.

Endothelial cells support survival, proliferation, and neuronal differentiation of transplanted adult ischemia-induced neural stem/progenitor cells after cerebral infarction.

Stem Cells. 2009; 27: 2185-2195

• Hlavac N.
• et al.

Progress toward finding the perfect match: hydrogels for treatment of central nervous system injury.

Mater. Today Adv. 2020; 6100039

• Emerich D.F.
• et al.

Injectable VEGF hydrogels produce near complete neurological and anatomical protection following cerebral ischemia in rats.

Cell Transplant. 2010; 19: 1063-1071

• Zhao Y.
• et al.

Clinical study of neuroregen scaffold combined with human mesenchymal stem cells for the repair of chronic complete spinal cord injury.

Cell Transplant. 2017; 26: 891-900

• Gorenkova N.
• et al.

In vivo evaluation of engineered self-assembling silk fibroin hydrogels after intracerebral injection in a rat stroke model.

ACS Biomater. Sci. Eng. 2019; 5: 859-869

• Williams D.F.

Challenges with the development of biomaterials for sustainable tissue engineering.

Front Bioeng Biotechnol. 2019; 7: 1-10

• Tong Z.
• et al.

Application of biomaterials to advance induced pluripotent stem cell research and therapy.

EMBO J. 2015; 34: 987-1008

• Boido M.
• et al.

Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment.

Sci. Rep. 2019; 9: 6402

• Ghuman H.
• et al.

Biodegradation of ECM hydrogel promotes endogenous brain tissue restoration in a rat model of stroke.

Acta Biomater. 2018; 80: 66-84

• Modo M.
• Badylak S.F.

A roadmap for promoting endogenous in situ tissue restoration using inductive bioscaffolds after acute brain injury.

Brain Res. Bull. 2019; 150: 136-149

• Bellotti E.
• et al.

Injectable thermoresponsive hydrogels as drug delivery system for the treatment of central nervous system disorders: a review.

J. Control. Release. 2021; 329: 16-35

• Osama I.
• et al.

In vitro studies on space-conforming self-assembling silk hydrogels as a mesenchymal stem cell-support matrix suitable for minimally invasive brain application.

Sci. Rep. 2018; 8: 1-11

• Moshayedi P.
• et al.

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain.

Biomaterials. 2016; 105: 145-155

• Liang Y.
• et al.

Label-free imaging of gelatin-containing hydrogel scaffolds.

Biomaterials. 2015; 42: 144-150

• Kalkowski L.
• et al.

Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells.

Pharmaceutics. 2021; 13: 1076

• Fisher M.
• et al.

Update of the stroke therapy academic industry roundtable preclinical recommendations.

Stroke. 2009; 40: 2244-2250

• Lovett M.
• et al.

Vascularization strategies for tissue engineering.

Tissue Eng. B Rev. 2009; 15: 353-370

• Massensini A.R.
• et al.

Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity.

Acta Biomater. 2015; 27: 116-130

• Budday S.
• et al.

Mechanical characterization of human brain tissue.

Acta Biomater. 2017; 48: 319-340

• Murphy W.L.
• et al.

Materials as stem cell regulators.

Nat. Mater. 2014; 13: 547-557

• Wen J.H.
• et al.

Interplay of matrix stiffness and protein tethering in stem cell differentiation.

Nat. Mater. 2014; 13: 979-987

• Nih L.R.
• et al.

Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke.

Nat. Mater. 2018; 17: 642-651

• Chen W.
• et al.

NeuroRegen scaffolds combined with autologous bone marrow mononuclear cells for the repair of acute complete spinal cord injury: a 3-year clinical study.

Cell Transplant. 2020; 29: 1-11

• Jin T.
• et al.

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.

Biomaterials. 2017; 113: 176-190

• Ghuman H.
• et al.

ECM hydrogel for the treatment of stroke: characterization of the host cell infiltrate.

Biomaterials. 2016; 91: 166-181

• Ghuman H.
• et al.

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume.

Acta Biomater. 2017; 63: 50-63

• Bible E.
• et al.

Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI.

Biomaterials. 2012; 33: 2858-2871

• Ghuman H.
• et al.

ECM hydrogel improves the delivery of PEG microsphere-encapsulated neural stem cells and endothelial cells into tissue cavities caused by stroke.

Brain Res. Bull. 2021; 168: 120-137

• Ho M.T.
• et al.

A hyaluronan/methylcellulose-based hydrogel for local cell and biomolecule delivery to the central nervous system.

Brain Res. Bull. 2019; 148: 46-54

• Austin J.W.
• et al.

High molecular weight hyaluronan reduces lipopolysaccharide mediated microglial activation.

J. Neurochem. 2012; 122: 344-355

• Austin J.W.
• et al.

The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis.

Biomaterials. 2012; 33: 4555-4564

• Cooke M.J.
• et al.

Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain.

Biomaterials. 2011; 32: 5688-5697

• Obermeyer J.M.
• et al.

Local delivery of brain-derived neurotrophic factor enables behavioral recovery and tissue repair in stroke-injured rats.

Tissue Eng. Part A. 2019; 25: 1175-1187

• Tuladhar A.
• et al.

Injectable hydrogel enables local and sustained co-delivery to the brain: two clinically approved biomolecules, cyclosporine and erythropoietin, accelerate functional recovery in rat model of stroke.

Biomaterials. 2020; 235119794

• Tuladhar A.
• et al.

Circumventing the blood-brain barrier: local delivery of cyclosporin A stimulates stem cells in stroke-injured rat brain.

J. Control. Release. 2015; 215: 1-11

• Ballios B.G.
• et al.

A hyaluronan-based injectable hydrogel improves the survival and integration of stem cell progeny following transplantation.

Stem Cell Reports. 2015; 4: 1031-1045

• Payne S.L.
• et al.

In vitro maturation of human iPSC-derived neuroepithelial cells influences transplant survival in the stroke-injured rat brain.

Tissue Eng. A. 2018; 24: 351-360

• Payne S.L.
• et al.

Initial cell maturity changes following transplantation in a hyaluronan-based hydrogel and impacts therapeutic success in the stroke-injured rodent brain.

Biomaterials. 2019; 192: 309-322

Reverse-engineered silk hydrogels for cell and drug delivery.

Ther. Deliv. 2018; 9: 469-487

• Yonesi M.
• et al.

Silk fibroin: An ancient material for repairing the injured nervous system.

Pharmaceutics. 2021; 13: 429-460

• Phuagkhaopong S.
• et al.

Silk hydrogel substrate stress relaxation primes mesenchymal stem cell behavior in 2D.

ACS Appl. Mater. Interfaces. 2021; 13: 30420-30433

• Fernández-García L.
• et al.

Safety and tolerability of silk fibroin hydrogels implanted into the mouse brain.

Acta Biomater. 2016; 45: 262-275

• Fernández-García L.
• et al.

Cortical reshaping and functional recovery induced by silk fibroin hydrogels-encapsulated stem cells implanted in stroke animals.

Front. Cell. Neurosci. 2018; 12: 1-16

• Martín-Martín Y.
• et al.

Evaluation of neurosecretome from mesenchymal stem cells encapsulated in silk fibroin hydrogels.

Sci. Rep. 2019; 9: 1-15

• Borlongan C.V.
• et al.

Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke.

Stroke. 2004; 35: 2206-2210

• Ansorena E.
• et al.

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury.

Int. J. Pharm. 2013; 455: 148-158

• des Rieux A.
• et al.

Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord.

J. Biomed. Mater. Res. A. 2013; 102: 2345-2355

• Distler T.
• et al.

Neuronal differentiation from induced pluripotent stem cell-derived neurospheres by the application of oxidized alginate-gelatin-laminin hydrogels.

Biomedicines. 2021; 9: 261

• Yan F.
• et al.

Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke.

Neural Regen. Res. 2015; 10: 1421-1426

• Ahmad N.
• et al.

Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia.

Int. J. Biol. Macromol. 2016; 91: 640-655

• Khodagholi F.
• et al.

Chitosan prevents oxidative stress-induced amyloid beta formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-kappaB.

Mol. Cell. Biochem. 2010; 337: 39-51

• Revkova V.A.
• et al.

Chitosan-g-oligo(L,L-lactide) copolymer hydrogel potential for neural stem cell differentiation.

Tissue Eng. A. 2020; 26: 953-963

• Worthington K.S.
• et al.

Neuronal differentiation of induced pluripotent stem cells on surfactant templated chitosan hydrogels.

Biomacromolecules. 2016; 17: 1684-1695

• Yao M.
• et al.

Chitosan-based thermosensitive composite hydrogel enhances the therapeutic efficacy of human umbilical cord MSC in TBI rat model.

Mater. Today Chem. 2019; 14: 1-12

• Chedly J.
• et al.

Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration.

Biomaterials. 2017; 138: 91-107

• Catoira M.C.
• et al.

Natural hydrogels R&D process: technical and regulatory aspects for industrial implementation.

J. Mater. Sci. Mater. Med. 2020; 31: 64

• Yannas I.V.

Emerging rules for inducing organ regeneration.

Biomaterials. 2013; 34: 321-330

• Faust A.
• et al.

Urinary bladder extracellular matrix hydrogels and matrix-bound vesicles differentially regulate central nervous system neuron viability and axon growth and branching.

J. Biomater. Appl. 2017; 31: 1277-1295

• Baumann M.D.
• et al.

Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury.

Biomaterials. 2010; 31: 7631-7639

• Gupta D.
• et al.

Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord.

Biomaterials. 2006; 27: 2370-2379

• Khoshnam S.E.
• et al.

Pathogenic mechanisms following ischemic stroke.

Neurol. Sci. 2017; 38: 1167-1186

• Liddelow S.A.
• et al.

Neurotoxic reactive astrocytes are induced by activated microglia.

Nature. 2017; 541: 481-487

• Hussey G.S.
• et al.

Extracellular matrix-based materials for regenerative medicine.

Nat. Rev. Mater. 2018; 3: 159-173

• Saldin L.T.
• et al.

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

Acta Biomater. 2017; 49: 1-15

• Freytes D.O.
• et al.

Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix.

Biomaterials. 2008; 29: 1630-1637

• Fallacara A.
• et al.

Hyaluronic acid in the third millennium.

Polymers (Basel). 2018; 10: 701

• Holland C.
• et al.

The biomedical use of silk: past, present, future.

Adv. Healthc. Mater. 2019; 8e1800465

• Yamada H.
• et al.

Identification of fibroin-derived peptides enhancing the proliferation of cultured human skin fibroblasts.

Biomaterials. 2004; 25: 467-472

• Puscaselu R.G.
• et al.

Alginate: from food industry to biomedical applications and management of metabolic disorders.

Polymers. 2020; 12: 2417

• Sikareepaisan P.
• et al.

Preparation and characterization of asiaticoside-loaded alginate films and their potential for use as effectual wound dressings.

Carbohydr. Polym. 2011; 83: 1457-1469

• Mirrahimi M.
• et al.

A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy.

Pharmacol. Res. 2019; 143: 178-185

• Cattelan G.
• et al.

Alginate formulations: current developments in the race for hydrogel-based cardiac regeneration.

Front. Bioeng. Biotechnol. 2020; 8: 414

• Montanari E.
• et al.

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters.

Xenotransplantation. 2021; 28e12666

• Ahmadi F.
• et al.

Chitosan based hydrogels: characteristics and pharmaceutical applications.

Res. Pharm. Sci. 2015; 10: 1-16

• Onsosyen E.
• Skaugrud O.

Metal recovery using chitosan.

J. Chem. Technol. Biotechnol. 1990; 49: 395-404

• Tang G.
• et al.

Recent advances of chitosan-based injectable hydrogels for bone and dental tissue regeneration.

Front. Bioeng. Biotechnol. 2020; 8: 1-15

• Feng P.
• et al.

Chitosan-based functional materials for skin wound repair: mechanisms and applications.

Front. Bioeng. Biotechnol. 2021; 9650598

• Liu H.
• et al.

A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing.

RSC Adv. 2018; 8: 7533-7549

• Du X.
• et al.

Injectable hydrogel composed of hydrophobically modified chitosan/ oxidized-dextran for wound healing.

Mater. Sci. Eng. C Mater. Biol. Appl. 2019; 104109930