Oct 18, 2016 | By Alec

3D bioprinting is often hailed as having the potential to revolutionize the medical world through regenerative implants, and could one day even lead to lab-grown organs and tissues. Several research teams around the world are already working on their own unique ways to 3D print cell structures, but all are faced with one significant obstacle: how do you 3D print a scaffolding in which the cells can live and grow into whatever you need them for? That obstacle is currently being tackled by researchers from the Moroni Lab at Maastricht University in the Netherlands, who have pioneered several 3D printable scaffold designs displaying the gradients necessary to influence the differentiation of adult stem cells towards skeletal cells.

This is a very important first step on the road towards 3D printed bone implants, and has come out of one of the largest biofabrication centers in Europe. The Moroni Lab was founded two years ago, as part of MERLN institute for Technology-Inspired Regenerative Medicine at Maastricht University. Their roots can be found at the University of Twente in 2009, when the research group was first set up. Since then, they have grown into a key member of the Brightlands ecosystem, which is working to establish new biomedical 3D printing programs in collaboration with clinical hospital departments. The Moroni Lab is further backed by various European initiatives and linked to various international biofabrication efforts.

As the Dutch researchers explain, their goal is the development of complete libraries of 3D scaffolds that can control the ‘fate’ of cells – whether they become skin cells, bone cells or anything else. This is a challenge faced by 3D printing, biomaterial, scaffold and surface property obstacles, but is also desperately needed. “First generation products consisted of cells in suspension, encapsulated in hydrogels, or seeded into 3D porous matrices. These products demonstrated the potential of regenerative medicine therapies by reducing pain and restoring tissue continuity. Yet, the regenerated tissue is not always as functional as the original one,” they explained. “This leads to degeneration a few years after surgery and consequently to the need of another surgery.”

The reasons for these limitations are manifold, but can be mostly traced back to the 3D environment that the cell proliferation and homeostasis requires. As the original cell phenotype is lost, the expanded cells produce a different extracellular matrix that does not correspond with the target tissue it should regenerate. “Furthermore, surgical procedures with these products typically consist of two steps, namely isolation and expansion of cells from a tissue biopsy and cell seeding on scaffolds prior to implantation. This is associated with long hospital stay and rehabilitation time, increasing healthcare costs as well,” they add.

It’s a problem that could be overcome with ‘smart constructs’ that can completely control the fate of the stem cells that are inserted, and could thus pave the way for a wide range of regenerative medicine applications. “Better control over cell-material interactions is necessary to maintain tissue engineered constructs in time. It is crucial to control stem cell quiescence, proliferation and differentiation in three-dimensional scaffolds while maintaining cells viable in situ,” they explain. 3D bioprinting could play a huge role in that, but the development of new technologies and hardware is absolutely essential.

But the lab’s latest achievements are an important step in the right direction. As they showcased in a series of papers, they already demonstrated how 3D printing can be used to design and fabricate scaffolds with embedded structural and physico-chemical gradients. These gradients are not only an additional scaffold component, but will also be able to influence the differentiation of adult stem cells towards bone cells. “We have shown how gradients in pore size and shape could aid in the differentiation of bone marrow derived adult mesenchymal stem (or stromal) cells towards skeletal lineages,” they say. “When MSCs are cultured in scaffolds with pores varying in size, they can be better differentiated towards osteoblasts or chondrocytes in presence of either chondrogenic or osteogenic media.”

What’s more, this is quite a flexible process. The pores on the scaffolds can be increased or decreased in size, creating osteogenic differentiation (when increased) or better chondrogeneiss (when decreased). “Similarly, when pore shape is varied from squared to increasingly rhomboidal shapes, MSCs shift their differentiation preference from the chondrogenic to the osteogenic lineage, respectively. Such influence on stem cell differentiation seems to be connected to different local nutrient availability, as shown by a differential expression of hypoxic inducible factors,” they add. This points to very exciting new 3D bioprinting strategies for implant development.

However, several other challenges still need to be tackled. Among others, the Moroni Lab will be working on integrating neural and vascular cues in tissue and organ regeneration strategies. This could be used to synthetically mimic peripheral nervous systems and could further stimulate tissue regeneration. What’s more, the researchers will be working on engineering immune responses to biomaterials and biomedical devices, while a lot more regenerative and degenerative phenomena still need to be studied from a biofabrication perspective. Here again, 3D printed constructs could play a vital research role and lead to improved constructs and new therapies.

This is thus very much a work-in-progress at the Moroni Lab in Maastricht, but crucial steps are being made on the road towards 3D bioprinted organ and tissue implants. To further support these efforts, the Lab (one of the largest of its kind in Europe) will also be launching an important program with the Brightlands Materials Center on 3D printing regenerative medicine applications later this week.

 

 

Posted in 3D Printing Technology

 

 

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