Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

• Publication year

  2017

• Venue

  Frontiers in Pharmacology

• Publication date

  2017-05-10

• Fields of study

  Medicine, Materials Science, Engineering

• Identifiers
  DOI 10.3389/fphar.2017.00245PMID 28539887PMCID 5423911
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A view from the ending: Axonal dieback and regeneration following SCI.

  2017cited by this paper
• Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release.

  2016cited by this paper
• Astrocyte roles in traumatic brain injury.

  2016cited by this paper
• Spinal Cord Injury (SCI) Facts and Figures at a Glance

  2016cited by this paper
• Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury

  2016cited by this paper
• Astrocyte scar formation aids central nervous system axon regeneration

  2016influential reference
• Electrospun Fibers for Spinal Cord Injury Research and Regeneration

  2016cited by this paper
• Electrospun Fibers for Drug Delivery after Spinal Cord Injury and the Effects of Drug Incorporation on Fiber Properties

  2016cited by this paper
• Spinal Cord Injury (SCI) Facts and Figures at a Glance

  2016cited by this paper
• Understanding the NG2 Glial Scar after Spinal Cord Injury

  2016cited by this paper
• Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury

  2015cited by this paper
• Multifunctional nanoparticles for gene delivery and spinal cord injury.

  2015cited by this paper
• Brain derived neurotrophic factor release from layer-by-layer coated agarose nerve guidance scaffolds.

  2015cited by this paper
• Cells Tissues Organs

  2015cited by this paper
• Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP)

  2015cited by this paper
• Macrophage and microglial plasticity in the injured spinal cord.

  2015cited by this paper
• Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

  2015cited by this paper
• Hybrid Crosslinked Methylcellulose Hydrogel: A Predictable and Tunable Platform for Local Drug Delivery

  2015cited by this paper
• Magnetic NGF-releasing PLLA/iron oxide nanoparticles direct extending neurites and preferentially guide neurites along aligned electrospun microfibers.

  2015cited by this paper
• Cell infiltration into a 3D electrospun fiber and hydrogel hybrid scaffold implanted in the brain

  2015cited by this paper
• Fibrin Gel as an Injectable Biodegradable Scaffold and Cell Carrier for Tissue Engineering

  2015cited by this paper
• Macrophage activation and its role in repair and pathology after spinal cord injury.

  2015influential reference
• Pharmacokinetics and Bioavailability of a Therapeutic Enzyme (Idursulfase) in Cynomolgus Monkeys after Intrathecal and Intravenous Administration

  2015cited by this paper
• Sustained dual drug delivery of anti-inhibitory molecules for treatment of spinal cord injury.

  2015cited by this paper
• Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite.

  2015cited by this paper
• Overcoming drug crystallization in electrospun fibers--Elucidating key parameters and developing strategies for drug delivery.

  2015cited by this paper
• Hydrogels and Cell Based Therapies in Spinal Cord Injury Regeneration

  2015cited by this paper
• Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue.

  2015cited by this paper
• An Injectable, Calcium Responsive Composite Hydrogel for the Treatment of Acute Spinal Cord Injury

  2014cited by this paper
• Repair of spinal cord injury by inhibition of astrocyte growth and inflammatory factor synthesis through local delivery of flavopiridol in PLGA nanoparticles.

  2014cited by this paper
• Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury.

  2014cited by this paper
• Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord.

  2014cited by this paper
• Design of hydrogel biomaterial interfaces for the injured spinal cord

  2014cited by this paper
• Function of microglia and macrophages in secondary damage after spinal cord injury

  2014cited by this paper
• Current perspectives on intrathecal drug delivery

  2014cited by this paper
• A characterization of white matter pathology following spinal cord compression injury in the rat.

  2014cited by this paper
• The current role of steroids in acute spinal cord injury.

  2014cited by this paper
• Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

  2014cited by this paper
• Repair of injured spinal cord using biomaterial scaffolds and stem cells

  2014cited by this paper
• Gelatin-carrageenan hydrogels: role of pore size distribution on drug delivery process.

  2014cited by this paper
• Advanced biomaterials for repairing the nervous system: what can hydrogels do for the brain?

  2014cited by this paper
• Progress of electrospun fibers as nerve conduits for neural tissue repair.

  2014cited by this paper
• Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation.

  2014influential reference
• Neutrophil contribution to spinal cord injury and repair

  2014cited by this paper
• Agarose drug delivery systems upgraded by surfactants inclusion: critical role of the pore architecture.

  2014cited by this paper
• Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

  2014cited by this paper
• Functional regeneration beyond the glial scar.

  2014cited by this paper
• Hydrogel drug delivery system with predictable and tunable drug release and degradation rates

  2013cited by this paper
• Affinity-based release of chondroitinase ABC from a modified methylcellulose hydrogel.

  2013cited by this paper
• Tracking Changes following Spinal Cord Injury

  2013cited by this paper
• Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene

  2013cited by this paper
• Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System

  2013cited by this paper
• Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury

  2013cited by this paper
• Tracking Changes following Spinal Cord Injury : Insights from Neuroimaging

  2013cited by this paper
• Current sustained delivery strategies for the design of local neurotrophic factors in treatment of neurological disorders

  2013cited by this paper
• Spinal Cord Injury: A Review of Current Therapy, Future Treatments, and Basic Science Frontiers

  2013cited by this paper
• Heparin crosslinked chitosan microspheres for the delivery of neural stem cells and growth factors for central nervous system repair.

  2013cited by this paper
• Influence of polymer processing technique on long term degradation of poly(ε-caprolactone) constructs

  2013cited by this paper
• Microglia response and in vivo therapeutic potential of methylprednisolone-loaded dendrimer nanoparticles in spinal cord injury.

  2013cited by this paper
• Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair.

  2013cited by this paper
• Nanoparticles for Brain Drug Delivery

  2013cited by this paper
• Sustained delivery of dbcAMP by poly(propylene carbonate) micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection.

  2013cited by this paper
• Characterization of hyaluronan-methylcellulose hydrogels for cell delivery to the injured spinal cord.

  2013cited by this paper
• Nanomedicine for treating spinal cord injury.

  2013cited by this paper
• Encapsulation of proteins in hydrogel carrier systems for controlled drug delivery: influence of network structure and drug size on release rate.

  2013cited by this paper
• Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair.

  2012cited by this paper
• Polymeric nanoparticles for drug delivery to the central nervous system.

  2012cited by this paper
• Tracking the changes: Textual scholarship and the challenge of the born digital

  2012cited by this paper
• In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury.

  2012cited by this paper
• The influence of fiber diameter of electrospun poly(lactic acid) on drug delivery

  2012cited by this paper
• Reduced antioxidant defense and increased oxidative stress in spinal cord injured patients.

  2012cited by this paper
• Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.

  2012cited by this paper
• Building Biocompatible Hydrogels for Tissue Engineering of the Brain and Spinal Cord

  2012cited by this paper
• Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury.

  2012cited by this paper
• PLGA-based nanoparticles: an overview of biomedical applications.

  2012cited by this paper
• Current therapeutic strategies for inflammation following traumatic spinal cord injury☆

  2012cited by this paper
• Inflammation & apoptosis in spinal cord injury

  2012influential reference
• Reactive Astrogliosis after Spinal Cord Injury—Beneficial and Detrimental Effects

  2012cited by this paper
• Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair.

  2012cited by this paper
• Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

  2012cited by this paper
• Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury.

  2011cited by this paper
• The stem cell potential of glia: lessons from reactive gliosis

  2011cited by this paper
• Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth

  2011cited by this paper
• Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward?

  2011cited by this paper
• Latest Approaches for the Treatment of Spasticity and Autonomic Dysreflexia in Chronic Spinal Cord Injury

  2011cited by this paper
• Transplantation of nanostructured composite scaffolds results in the regeneration of chronically injured spinal cords.

  2011cited by this paper
• Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade.

  2011cited by this paper
• A Pericyte Origin of Spinal Cord Scar Tissue

  2011cited by this paper
• Electrospun Nanofibrous Materials for Neural Tissue Engineering

  2011cited by this paper
• Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers.

  2011cited by this paper
• Tunable Growth Factor Delivery from Injectable Hydrogels for Tissue Engineering

  2011cited by this paper
• Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels

  2011cited by this paper
• Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury.

  2010cited by this paper
• Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers.

  2010cited by this paper
• Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds.

  2010cited by this paper
• Varying the diameter of aligned electrospun fibers alters neurite outgrowth and Schwann cell migration.

  2010cited by this paper
• Injectable biodegradable hydrogels.

  2010cited by this paper
• A systematic review of pharmacologic treatments of pain after spinal cord injury.

  2010cited by this paper
• Electrospun poly(D,L‐lactide) fibers for drug delivery: The influence of cosolvent and the mechanism of drug release

  2010cited by this paper
• Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

  2010influential reference

• Epidural Thin Film Implants of Polymerized Curcumin Downregulate Inflammatory Markers and Improve Functional Recovery After Spinal Cord Injury in Mice

  2026cites this paper
• Central Nervous System Targeting Nanovesicles for Trans-Barrier Delivery and Spinal Cord Injury Treatment.

  2025cites this paper
• Polymerized Pro-Estrogen Microneedles via Two Photon Polymerization.

  2025cites this paper
• Targeting Glycolysis for Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Prospects.

  2025cites this paper
• Positively Charged Polyurethane Scaffolds Reshape the Microenvironment to Promote Endogenous Regeneration after Brain Injury.

  2025cites this paper
• Induction of M2 Macrophages by Fibrin Hydrogels Enhances Bone Regeneration

  2025cites this paper
• Green Synthesis, Chemical Characterization, and Assessment of the Neuroprotective Properties of Zinc Nanoparticles on the Spinal Cord Injury Contusive Model in Rats.

  2025cites this paper
• Trends in the application of chondroitinase ABC in injured spinal cord repair

  2025cites this paper
• Modular molecular design of polymerized pro-estrogen materials enables controlled astrocyte response

  2025cites this paper
• Determining Ultrasound Parameters for Bursting Polymer Microbubbles for Future Use in Spinal Cord Injury.

  2024cites this paper
• Mechanisms and Therapeutic Prospects of Microglia-Astrocyte Interactions in Neuropathic Pain Following Spinal Cord Injury

  2024cites this paper
• Complement C5a Implication in Axonal Growth After Injury

  2024cites this paper
• Acrylic Acid Modified Poly-ethylene Glycol Microparticles for Affinity-Based release of Insulin-Like Growth Factor-1 in Neural Applications

  2024cites this paper
• Carbohydrates and neurotrophic factors: A promising partnership for spinal cord injury rehabilitation.

  2024cites this paper
• Delivery of TGFβ3 from Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro

  2024cites this paper
• Nanomaterials for the treatment of spinal cord injury

  2024cites this paper
• The global state of research in stem cells therapy for spinal cord injury (2003–2022): a visualized analysis

  2024cites this paper
• Current insights into the management of spinal cord injury.

  2023cites this paper
• Traumatic Human Spinal Cord Injury: Are Single Treatments Enough to Solve the Problem?

  2023cites this paper
• Chondroitinase as a therapeutic enzyme: Prospects and challenges.

  2023cites this paper
• Sustained neurotrophin-3 delivery from hyaluronic acid hydrogels for neural tissue regeneration.

  2023cites this paper
• In Situ Cross-Linkable Hyaluronic-Ferulic Acid Conjugate Containing Bucladesine Nanoparticles Promotes Neural Regeneration after Spinal Cord Injury.

  2023cites this paper
• Building a Pathway to Recovery: Targeting ECM Remodeling in CNS Injuries.

  2023cites this paper
• An artificial silk elastin-like protein modifies the polarization of human macrophages line THP-1

  2023cites this paper
• Individually Tailored Modular “Egg” Hydrogels Capable of Spatiotemporally Controlled Drug Release for Spinal Cord Injury Repair

  2023cites this paper
• Drug-Loaded Zwitterion-Based Nanomotors for the Treatment of Spinal Cord Injury.

  2023cites this paper
• Application of Conductive Hydrogels on Spinal Cord Injury Repair: A Review.

  2023cites this paper
• Intrathecal delivery of Macromolecules: Clinical status and emerging technologies.

  2023cites this paper
• Biofunctionalization of hydrogel-based scaffolds for vascular tissue regeneration

  2023cites this paper
• Red blood cell-like magnetic particles and magnetic field promoted neuronal outgrowth by activating Netrin-1/DCC signaling pathway in vitro and in vivo

  2022cites this paper
• Heterogeneous pHPMA hydrogel promotes neuronal differentiation of bone marrow derived stromal cells in vitro and in vivo

  2022cites this paper
• An Artificial Silk Elastin-Like Protein Modifies the Polarization of Macrophages.

  2022cites this paper
• Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment

  2022cites this paper
• Localized, on-demand, sustained drug delivery from biopolymer-based materials

  2022cites this paper
• Biomaterial-Mediated Factor Delivery for Spinal Cord Injury Treatment

  2022cites this paper
• Development and Application of Three-Dimensional Bioprinting Scaffold in the Repair of Spinal Cord Injury

  2022cites this paper
• Multivariate analysis reveals topography dependent relationships amongst neurite morphological features from dorsal root ganglia neurons

  2022cites this paper
• Determination of Sr2+ mobility in viscous bovine bone marrow by cryo-time-of-flight secondary ion mass spectrometry.

  2022cites this paper
• Citicoline–liposome/polyurethane composite scaffolds regulate the inflammatory response of microglia to promote nerve regeneration

  2022influential citation
• On the therapeutic targets and pharmacological treatments for pain relief following spinal cord injury: A mechanistic review.

  2021cites this paper
• Electrospun bioactive composites for neural tissue engineering applications

  2021cites this paper
• Hydrogels as delivery systems for spinal cord injury regeneration

  2021cites this paper
• Nanoparticle-Based Delivery to Treat Spinal Cord Injury—a Mini-review

  2021cites this paper
• Neurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissue

  2021cites this paper
• Novel nanoformulated combination of Se and CeO 2 particles loaded polylactic‐co‐glycolic acid vesicle to improved anti‐inflammation and auto‐regenerative for the treatment and care of spinal cord injury

  2021cites this paper
• Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro.

  2021cites this paper
• Extracellular Matrix‐Mimetic Hydrogels for Treating Neural Tissue Injury: A Focus on Fibrin, Hyaluronic Acid, and Elastin‐Like Polypeptide Hydrogels

  2021cites this paper
• Plant Derived Cellulose Scaffolds as a Novel Biomaterial for 3D Cell Culture and Tissue Regeneration

  2021cites this paper
• Novel design and combination strategy of minocycline and OECs-loaded CeO2 nanoparticles with SF for the treatment of spinal cord injury: In vitro and in vivo evaluations

  2021cites this paper
• Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape

  2021cites this paper
• Application and progress of three‐dimensional bioprinting in spinal cord injury

  2021cites this paper
• Pharmacological therapies and factors delivery for spinal cord injury regeneration

  2020cites this paper
• Fundamentals and application of modeling in support of spinal cord injury repair strategies

  2020cites this paper
• Evolution of drug-eluting biomedical implants for sustained drug delivery.

  2020influential citation
• Regenerative Rehabilitation with Conductive Biomaterials for Spinal Cord Injury.

  2020cites this paper
• Biomaterial-based systems as biomimetic agents in the repair of the central nervous system

  2020cites this paper
• Design of hydrogel-based scaffolds for the treatment of spinal cord injuries.

  2020cites this paper
• Plant Scaffolds Support Motor Recovery and Regeneration in Rats after Traumatic Spinal Cord Injury

  2020cites this paper
• Hydrogel-based local drug delivery strategies for spinal cord repair

  2020cites this paper
• Mechanical properties of the spinal cord and brain: Comparison with clinical-grade biomaterials for tissue engineering and regenerative medicine.

  2020cites this paper
• A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury.

  2020cites this paper
• Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials.

  2020cites this paper
• Novel innovations in cell and gene therapies for spinal cord injury

  2020cites this paper
• Formulation of thrombin-inhibiting hydrogels via self-assembly of ionic peptides with peptide-modified polymers.

  2020cites this paper
• Cell and Tissue Instructive Materials for Central Nervous System Repair

  2020cites this paper
• Ex Vivo Rat Transected Spinal Cord Slices as a Model to Assess Lentiviral Vector Delivery of Neurotrophin-3 and Short Hairpin RNA against NG2

  2020cites this paper
• Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

  2020cites this paper
• Soft and rigid scaffolds for spinal cord injury regeneration

  2020cites this paper
• Motor and sensitive recovery after injection of a physically cross-linked PNIPAAm-g-PEG hydrogel in rat hemisectioned spinal cord.

  2020cites this paper
• How can nanovectors be used to treat spinal cord injury?

  2019cites this paper
• Bone marrow mesenchymal stem cells encapsulated thermal-responsive hydrogel network bridges combined photo-plasmonic nanoparticulate system for the treatment of urinary bladder dysfunction after spinal cord injury.

  2019cites this paper
• Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

  2019cites this paper
• Regenerative Therapies for Spinal Cord Injury

  2019cites this paper
• Biomaterials for Sustained and Controlled Delivery of Small Drug Molecules

  2019cites this paper
• Novel Delivery Systems for Checkpoint Inhibitors

  2019cites this paper
• Magnetic Composite Biomaterials for Neural Regeneration

  2019influential citation
• Stabilized Interleukin-4-Loaded Poly(lactic-co-glycolic) Acid Films Shift Proinflammatory Macrophages toward a Regenerative Phenotype in Vitro.

  2019cites this paper
• Preparation of fibrin hydrogels to promote the recruitment of anti-inflammatory macrophages.

  2019cites this paper
• Biomaterials for local drug delivery in central nervous system

  2019cites this paper
• An anti-inflammatory peptide and brain-derived neurotrophic factor-modified hyaluronan-methylcellulose hydrogel promotes nerve regeneration in rats with spinal cord injury

  2019cites this paper
• Recent advances in musculoskeletal local drug delivery.

  2019cites this paper
• Direct targeting of the mouse optic nerve for therapeutic delivery.

  2019cites this paper
• Poly-l-lactic acid-co-poly(pentadecalactone) Electrospun Fibers Result in Greater Neurite Outgrowth of Chick Dorsal Root Ganglia in Vitro Compared to Poly-l-lactic Acid Fibers.

  2018cites this paper
• Reducing inflammation through delivery of lentivirus encoding for anti‐inflammatory cytokines attenuates neuropathic pain after spinal cord injury

  2018cites this paper
• Component 1 : Selection of Restoration-Permissive Stroke Models Large Territorial Ischemic Lesions

  2018cites this paper
• Polyethylene glycol in spinal cord injury repair: a critical review

  2018cites this paper
• Application of PLGA/FGF-2 coaxial microfibers in spinal cord tissue engineering: an in vitro and in vivo investigation.

  2018cites this paper
• Localized immunomodulation of IL-10 and IL-4 to enhance functional regeneration after spinal cord injury

  2018cites this paper
• Synthesis of monomers for the biochemical investigation of plant polyesters

  2018cites this paper
• Response of macrophages and neural cells in contact with reduced graphene oxide microfibers.

  2018cites this paper
• Local Immunomodulation with Anti-inflammatory Cytokine-Encoding Lentivirus Enhances Functional Recovery after Spinal Cord Injury.

  2018cites this paper
• Future of Animal Modeling for Poststroke Tissue Repair.

  2018cites this paper
• Carbonyl scavengers as pharmacotherapies in degenerative disease: Hydralazine repurposing and challenges in clinical translation.

  2018cites this paper
• Minimally Invasive and Regenerative Therapeutics

  2018cites this paper
• Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

  2017cites this paper
• Strontium release from Sr2+-loaded bone cements and dispersion in healthy and osteoporotic rat bone.

  2017cites this paper