4.7 Review

Natural Biomaterials as Instructive Engineered Microenvironments That Direct Cellular Function in Peripheral Nerve Tissue Engineering

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2021.674473

Keywords

peripheral nerve; tissue engineering; biomaterials; microenvironment; regeneration

Funding

  1. Medical Research Council (MRC) [MR/N013867/1]
  2. UCL Mechanical Engineering
  3. Advanced Therapeutics and Nano-medicines CDT [EP/L01646X, EP/R004463/1]

Ask authors/readers for more resources

This review discusses the physical processes by which natural biomaterials mimic the function of the extracellular matrix and regulate cellular behavior, as well as highlights representative cases of controllable cell microenvironments developed through the combination of cell biology and tissue engineering principles.
Nerve tissue function and regeneration depend on precise and well-synchronised spatial and temporal control of biological, physical, and chemotactic cues, which are provided by cellular components and the surrounding extracellular matrix. Therefore, natural biomaterials currently used in peripheral nerve tissue engineering are selected on the basis that they can act as instructive extracellular microenvironments. Despite emerging knowledge regarding cell-matrix interactions, the exact mechanisms through which these biomaterials alter the behaviour of the host and implanted cells, including neurons, Schwann cells and immune cells, remain largely unclear. Here, we review some of the physical processes by which natural biomaterials mimic the function of the extracellular matrix and regulate cellular behaviour. We also highlight some representative cases of controllable cell microenvironments developed by combining cell biology and tissue engineering principles.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

Materials for peripheral nerve repair constructs: Natural proteins or synthetic polymers?

Holly Gregory, James B. Phillips

Summary: Efforts to repair severe peripheral nerve injuries have led to promising approaches using biomaterial constructs. Research is focused on developing sophisticated constructs with regenerative agents to facilitate nerve regeneration. The use of natural proteins and synthetic polymers in nerve repair constructs, as well as cell therapy, show potential for successful outcomes in vivo.

NEUROCHEMISTRY INTERNATIONAL (2021)

Article Engineering, Biomedical

Engineered aligned endothelial cell structures in tethered collagen hydrogels promote peripheral nerve regeneration

Papon Muangsanit, Victoria Roberton, Eleni Costa, James B. Phillips

Summary: Vascularisation is crucial for nerve tissue engineering to support long-term survival of implanted cells. Constructs containing endothelial cells have shown to promote axonal regeneration and vascularisation across peripheral nerve gaps.

ACTA BIOMATERIALIA (2021)

Article Chemistry, Multidisciplinary

An alginate-based encapsulation system for delivery of therapeutic cells to the CNS

Despoina Eleftheriadou, Rachael E. Evans, Emily Atkinson, Ahmed Abdalla, Francesca K. H. Gavins, Ashleigh S. Boyd, Gareth R. Williams, Jonathan C. Knowles, Victoria H. Roberton, James B. Phillips

Summary: This study developed a novel approach for protecting cells implanted into the central nervous system by using dual-layer alginate beads. The beads act as a sustained physical barrier, preventing host immune responses while allowing exchange of small molecules. Additionally, an immunosuppressant, FK506, was incorporated into the outer layer of the beads, enabling prolonged release to further protect the implanted cells. This research has the potential to be an effective treatment method in CNS cell delivery.

RSC ADVANCES (2022)

Article Biotechnology & Applied Microbiology

A combined experimental and computational framework to evaluate the behavior of therapeutic cells for peripheral nerve regeneration

Despoina Eleftheriadou, Maxime Berg, James B. Phillips, Rebecca J. Shipley

Summary: Recent studies have focused on investigating the potential benefits of tissue-mimetic scaffolds in promoting nerve regeneration. The interaction between cells and their microenvironment is a critical factor for the success of cellular nerve repair constructs. This study evaluates the differences in cellular behavior induced by different environmental conditions in vitro and proposes a mathematical model to describe these interactions.

BIOTECHNOLOGY AND BIOENGINEERING (2022)

Article Engineering, Biomedical

Engineered neural tissue made using hydrogels derived from decellularised tissues for the regeneration of peripheral nerves

Simon C. Kellaway, Victoria Roberton, Joshua N. Jones, Rabea Loczenski, James B. Phillips, Lisa J. White

Summary: Incorporating dECMh derived from bone, liver, and small intestinal tissues can promote neurite extension and axonal regeneration, providing an alternative to current collagen I hydrogel.

ACTA BIOMATERIALIA (2023)

Article Biochemistry & Molecular Biology

Culture Conditions for Human Induced Pluripotent Stem Cell-Derived Schwann Cells: A Two-Centre Study

Zhong Huang, Rebecca Powell, Svenja Kankowski, James B. Phillips, Kirsten Haastert-Talini

Summary: Researchers have successfully generated Schwann cells from human induced pluripotent stem cells by modifying existing protocols, resulting in sufficient cell numbers. They also found that specific coating and glucose levels are crucial for improving the differentiation process and increasing the yield of viable cells.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Clinical Neurology

Serum neurofilament light chain measurements following nerve trauma

Matthew Wilcox, Melissa L. D. Rayner, Owein Guillemot-Legris, Isobel Platt, Hazel Brown, Tom Quick, James B. Phillips

Summary: Early detection and prompt referral to specialist centres for surgical intervention are crucial for optimal functional recovery following peripheral nerve injuries (PNIs). Serum Neurofilament light chain (NfL) measurements offer a promising method for detecting and stratifying the severity of traumatic PNI, providing a powerful tool to improve surgical management of nerve-injured patients.

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM (2023)

Article Biochemistry & Molecular Biology

Local Administration of Minocycline Improves Nerve Regeneration in Two Rat Nerve Injury Models

Owein Guillemot-Legris, Gedion Girmahun, Rebecca J. Shipley, James B. Phillips

Summary: Peripheral nerve injuries are common and often require surgery, but patients often do not regain satisfactory sensory and motor functions. This causes a heavy socioeconomic burden. We investigated the effects of locally delivering minocycline on nerve regeneration and found that it improved the outcome.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Cell & Tissue Engineering

Electrospun aligned tacrolimus-loaded polycaprolactone biomaterials for peripheral nerve repair

Holly N. Gregory, Owein Guillemot-Legris, Daisy Crouch, Gareth Williams, James B. Phillips

Summary: This article explores the potential of fibrous materials loaded with tacrolimus for the surgical repair of peripheral nerve injury. The materials exhibit sustained drug release, modulate the gene expression of Schwann cells, and promote directional outgrowth of neurons.

REGENERATIVE MEDICINE (2023)

Article Multidisciplinary Sciences

Mathematical modelling with Bayesian inference to quantitatively characterize therapeutic cell behaviour in nerve tissue engineering

Maxime Berg, Despoina Eleftheriadou, James B. Phillips, Rebecca J. Shipley

Summary: Cellular engineered neural tissues have the potential to improve peripheral nerve repair strategies. Mathematical cell-solute models benchmarked against experimental data enable computational experiments, accelerating the development of new treatment strategies.

JOURNAL OF THE ROYAL SOCIETY INTERFACE (2023)

Article Materials Science, Multidisciplinary

Improving the biological interfacing capability of diketopyrrolopyrrole polymers via p-type doping

Ryan P. Trueman, Peter Gilhooly Finn, Megan M. Westwood, Avishek Dey, Robert Palgrave, Alethea Tabor, James B. Phillips, Bob C. Schroeder

Summary: This study investigates the effects of molecular doping on the surface properties of polydiketopyrrolopyrrole terthiophene (DPP3T) thin films and its subsequent impact on Schwann cell behavior. The results demonstrate that molecular doping alters the topography of DPP3T films, leading to increased cell numbers and larger, more spread out cell morphology. Furthermore, the viability of the cells on the doped films remains unaffected.

JOURNAL OF MATERIALS CHEMISTRY C (2023)

Review Medicine, Research & Experimental

Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models

Simao Laranjeira, Victoria H. H. Roberton, James B. B. Phillips, Rebecca J. J. Shipley

Summary: Drug therapies for peripheral nerve injury repair have shown promise in preclinical studies, but are not routinely used clinically. Systemic drug delivery often leads to adverse effects, making it challenging to determine effective concentration and delivery strategy. Mathematical modeling can inform transport mechanisms and predict the efficacy of local delivery protocols, accelerating the development of drug delivery approaches for peripheral nerve injury repair.

WIRES MECHANISMS OF DISEASE (2023)

Meeting Abstract Cell & Tissue Engineering

COMPARING THE PERIPHERAL NERVE REGENERATIVE POTENTIAL OF SCHWANN CELL PRECURSORS AND SCHWANN CELLS DIFFERENTIATED FROM HUMAN IPSCS

Rebecca Powell, Parmjit Jat, Rickie Patani, Kristjan Jessen, James B. Phillips

TISSUE ENGINEERING PART A (2022)

Article Multidisciplinary Sciences

In silico framework to inform the design of repair constructs for peripheral nerve injury repair

S. Laranjeira, G. Pellegrino, K. S. Bhangra, J. B. Phillips, R. J. Shipley

Summary: Peripheral nerve injuries impact millions annually, often resulting in loss of sensation and muscle control. Current treatment with nerve autografts has limitations, driving the need for alternatives like engineered nerve replacement tissues. However, challenges remain in optimizing materials and cell arrangement for maximal regeneration rates, hindered by reliance on experimental testing due to time and cost constraints.

JOURNAL OF THE ROYAL SOCIETY INTERFACE (2022)

No Data Available