Hydrogels for brain repair: application to Parkinson’s disease

ABSTRACT

Introduction

Parkinson’s disease is the second most common neurodegenerative disease. Currently, there are no curative therapies, with only symptomatic treatment available. One of the principal reasons for the lack of treatments is the problem of delivering drugs to the brain, mainly due to the blood-brain barrier. Hydrogels are presented as ideal platforms for delivering treatments to the brain ranging from small molecules to cell replacement therapies.

Areas covered

The potential application of hydrogel-based therapies for Parkinson’s disease is addressed. The desirable composition and mechanical properties of these therapies for brain application are discussed, alongside the preclinical research available with hydrogels in Parkinson’s disease. Lastly, translational and manufacturing challenges are presented.

Expert opinion

Parkinson’s disease urgently needs novel therapies to delay its progression and for advanced stages, at which conventional therapies fail to control motor symptoms. Neurotrophic factor-loaded hydrogels with stem cells offer one of the most promising therapies. This approach may increase the striatal dopamine content while protecting and promoting the differentiation of stem cells although the generation of synapses between engrafted and host cells remains an issue to overcome. Other challenges to consider are related to the route of administration of hydrogels and their large-scale production, required to accelerate their translation toward the clinic.

KEYWORDS:

• Parkinson’s disease
• hydrogels
• rheological properties
• drug delivery
• protein therapy
• neurotrophic factors
• pluripotent stem cells
• cell transplantation

Article highlights

• Parkinson’s disease requires treatments that have long-lasting clinical benefits and treat the cause of the disease, not only the symptoms.

• Hydrogels are biocompatible and tunable biomaterials with interesting advantages over other delivery systems.

• To be used in the treatment of Parkinson’s disease, locally administered hydrogels must mimic not only the composition of the brain but also its mechanical properties.

• Several studies have evaluated the efficacy of combining hydrogels with different molecules, proteins, and cells.

• The combination of neurotrophic factors and dopaminergic progenitors within hydrogels offers the best in vivo outcomes.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosrues

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

E. Garbayo is supported by a “Ramon y Cajal Fellowship” (RYC2018-025897-I). R. del Campo-Montoya is beneficiary of a pre-doctoral fellowship of the “Asociación de Amigos de la Universidad de Navarra”. This work was supported by the Gobierno de Navarra. Departamento de Salud 64/2019 (co-financed at 50% by the European Regional Development Fund through the FEDER Operational Program 2014-2020 of Navarra: “European Union”.