Marrying Nanomedicine and Tissue Engineering

How nanomedicine and tissue engineering are colliding to create a regenerative duo.

The field of tissue engineering has advanced in the last 15 years, offering the potential for regenerating almost every tissue and organ of the human body. Among current clinical applications are the production of artificial skin for burn patients, tissue engineered trachea and blood vessels, cartilage for knee-replacement procedures, urinary bladder replacement, urethra substitutes and cellular therapies for the treatment of urinary incontinence. With the development of enabling technologies – specially in the field of micro and nanotechnology – tissue engineering is now increasingly overlapping with nanomedicine, as they share common applications.

Synthesizing scaffolds

General strategies for tissue engineering involve the implantation of isolated cells, tissue-inducing biologics or cell substitutes into the organism, with or without the use of 3D synthetic constructs – commonly referred to as scaffolds or matrices. Scaffolds are porous solid biomaterials designed to perform some or all of the following functions:

  • Promote cell-biomaterial interactions, cell adhesion and extracellular deposition
  • Allow transport of gases, nutrients and factors for cell survival, proliferation and differentiation
  • Degrade at a controllable rate that is optimal for tissue regeneration, without inflammation or toxicity

Developing scaffolds that mimic the architecture of tissue at the nanoscale is one of the major challenges in the field. Luckily, the recent development of nanofibres has greatly enhanced the scope for fabricating scaffolds, as nanofibres can potentially mimic the architecture of natural human tissues and microporous structures to favour cell adhesion, proliferation, migration and differentiation.

Safe and effective

In regenerative medicine, the prior manipulation of individual cells in vitro and its combination with biomaterials that provide scaffolding support, highlight the complexity of safety and efficacy issues. Similar issues arise with direct in situ injections. Are the cells localised in the appropiate site? How may they survive, migrate and differentiate?

Novel nanocontrast agents, as well as their combined use with cell proucts, can help document quality control and therapeutic effect. In this context, the use of magnetic resonance imaging (MRI) may improve the monitoring of implanted cells. The addition of nanosystems to advanced therapy medicinal products (ATMPs) can be either an integral part of therapeutic interventions (eg. magnetic targeting; theranostics with drug) or a tool for efficacy control (imaging agent for cell tracking). The most commonly used MRI contrast agents are superparamagnetic iron oxide nanoparticles. Iron oxide nanoparticles may facilitate cell tracking while remaining inert. Nanoformulated materials are thus an active area of R&D.

On the horizon

Medicinal products based on tissue engineering are classified as ATMPs. At present, ATMPs present major scientific, regulatory and economic challenges. Numerous questions have to be answered before the engineering of tissue and organs can become routine practice.

Nanotechnologies clearly have an impact on tissue engineering. First, the natural niche of cells is structurally hierarchical and nanocomposite in nature. Understanding this niche and taking the biomimicking route should bring improvements to the field of tissue engineering. This progress is parallel to the advancement of tools that effectively probe, monitor, characterise and understand living constructs. As regulators have recognised the importance of cell tracking in the context of ATMPs, novel approaches should be developed to improve safety and detection, and allow for clinical translation.

Both fields have yet to produce profitable products. Although nanoparticle-based therapy is becoming more common in the tratment of cancer, integrating a nanosystem into the constructs of tissue engineering has so far proved challenging and has not yet been clinically validated. Both nanomedicine and tissue engineering – as quite recent emerging fields – are clearly having difficulty transitoring from academic research to industrial phases and successful products. However, they are bringing together various disciplines and clinically relevant approaches. This is currently one exciting challenge for academic and industrial developers.

Article published by Dr Didier Letourneur, head of the Cardiovascular Bio-engineering Laboratory at INSERM and member of theEuropean Technology Platform on Nanomedicine in the International Innovation publication (Issue 133)