Hi guys! As we discussed in class this week, tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development.

Engineering a functional tissue is difficult. Cells must be organized into tissues with structural and physiological features resembling actual structures in the body. The outer connective tissue that supports cells, known as the extracellular matrix, is especially interesting to us. The matrix and its components — fibers, adhesion proteins, proteoglycans and others — provide cells with a wealth of information that regulates cell growth, shape, migration and differentiation.

To mimic these physiologic features, scientists have been working at the nanoscale – creating structures at the range of 1 billionth of a meter, 100 times smaller than a red blood cell. Through techniques like electrospinning and self-assembly, they can fabricate scaffolds with fibers of the appropriate thickness that form an interconnected, porous architecture. They can modify surfaces by attaching proteins, peptides and other molecules that enhance cell spreading and differentiation. They can increase concentrations of growth factors and cytokines in the engineered tissue by adding charged coatings to which they could stick. Finally, they can modify the 3D shape of the extracellular matrix surface to influence cell shape, differentiation and adhesion.

Nanomaterials can also compensate for limitations in the scaffold. Embedding nanoparticles in biomaterials can enhance their mechanical and electrical conductive properties, for example. Nanomaterials can also increase cell viability, promote adhesion, control the release of growth factors and cytokines, and even physically shape biomaterials and cells to create a desired tissue structure.

Once we engineer a tissue, nanodevices can be useful for triggering desired biological functions and for monitoring engineered tissues before transplantation, to ensure they will function as intended. Nanowires can record the electronic signals that are transmitted through brain cells and cardiac muscle cells for example, or monitor, in real time, the concentration of chemicals of interest within the scaffold. For instance, silicon nanowires with antibodies coupled to their surface have been used to selectively detect biomolecules in serum at femtomolar-level concentrations (a billionth of a millionth of a mole).

Although nanotechnologies have clearly had an impact on tissue engineering, challenges remain. Creating scaffolds with complicated 3D nanoscale surface structures is one challenge. We also need to further explore the biocompatibility and biodegradation of inorganic nanomaterials before they can be safely used clinically.

We’re excited about a future where intelligent nanosensors could be incorporated into engineered tissue to monitor tissue behavior and to trigger the release of biomolecules that promote tissue development and growth. Where nanowired neuroprostheses could assist paralyzed patients by re-routing movement-related signals around injured parts of the nervous system. Where nanomaterials on a tissue’s outer surface could reduce inflammatory responses to transplantation.

Ultimately, smart controllable nanorobots could potentially go to work for us — circulating inside the body, finding diseased tissues and repairing them by destroying defected cells and molecules or by encouraging cells to regain their function. We believe that these tiny nanostructures could redefine medicine in the future. It’s a future I look forward to being a part of.

References:
Dvir, Tal, et al. “Nanotechnological strategies for engineering complex tissues.” Nature nanotechnology 6.1 (2011): 13.
Sethuraman, Swaminathan, Uma Maheswari Krishnan, and Anuradha Subramanian, eds. Biomaterials and Nanotechnology for Tissue Engineering. CRC Press, 2016.

Hi guys! This week in class, we learned that the emerging field of tissue Engineering involves replacing, repairing or enhancing biological function at the scale of a tissue or organ by manipulating cells via their extracellular environment.From my understanding, tissue engineering intends to help the body to produce a material that resembles as much as possible the body’s own native tissue.

Scaffolds are often used in tissue engineering. They serve as temporary or permanent artificial Extracellular Matrices (ECM) to accommodate cells and support 3D tissue regeneration. They can also serve as delivery vehicles for exogenous cells, growth factors and genes and as a matrix for cell adhesion. They structurally reinforce the defect to maintain the shape of the defect and prevent distortion of surrounding tissues and act as a barrier to prevent the infiltration of surrounding tissues that may impede the regeneration process.

In general, the requirements of scaffolds for tissue engineering are:
(i) Three-dimensional and highly porous with an interconnected pore network for cell growth and flow transport of nutrients and metabolic waste.
(ii) Biocompatible and bioresorbable with a controllable degradation and resorption rate to match cell/tissue growth in vitro and/or in vivo.
(iii) Suitable surface chemistry for cell attachment, proliferation, and differentation .
(iv) Mechanical properties to match those of the tissues at the site of implantation.

Figure 1. Examples of trabecular scaffolds

Metallic scaffolds have been widely used in tissue engineering because of their good mechanical properties. The main disadvantage of metallic biomaterials is their lack of biological recognition on the material surface. To overcome this restraint, surface coating or surface modification presents a way to preserve the mechanical properties of established biocompatible metals improving the surface biocompatibility. Another limitation of the current metallic biomaterials is the possible release of toxic metallic ions and/or particles through corrosion or wear that lead to inflammatory cascades and allergic reactions, which reduce the biocompatibility and cause tissue loss.

One example of metallic scaffold is tantalum scaffold. Porous tantalum is a biomaterial with a unique set of physical and mechanical properties.It has a high-volume porosity (>80%) with fully interconnected pores to allow secure and rapid bone ingrowth. Studies have demonstrated substantial cortical bone ingrowth between the trabecular network as well as high levels of bone growth onto the scaffold itself. Initial stability of the trabecular metal itself is also higher than that of standard materials, such as cobalt chrome. Furthermore, this new material offers better osteoconduction than other technologies used for biological fixation.

Figure 2. Tantalum scaffolds

Titanium is found to be well tolerated and nearly an inert material in the human body environment.In an optimal situation titanium is capable of osseointegration with bone. In addition, titanium forms a very stable passive layer of TiO2 on its surface and provides superior biocompatibility. The nature of the oxide film that protects the metal substrate from corrosion is of particular importance. In general, porous titanium and titanium alloys exhibit good biocompatibility. Bioactive titanium meshes have been successfully used in spine fusion surgery for the past two decades.

Figure 3. Titanium scaffolds

Future directions of research in metallic scaffold will probably focus on the efficient combinations of osteoinductive materials, osteoinductive growth factors and cell-based tissue regeneration approach using composite constructs carriers to reconstruct and repair hard tissues. The goal is to obtain a functional replacement of the injured hard tissue in a procedure that avoids the step of bone harvesting.

References:
[1] Meyer, Ulrich, et al., eds. Fundamentals of tissue engineering and regenerative medicine. Springer Science & Business Media, 2009.
[2] Pallua, Norbert, and Christoph V. Suschek, eds. Tissue engineering: from Lab to Clinic. Springer Science & Business Media, 2010.
[3] Alvarez, Kelly, and Hideo Nakajima. “Metallic scaffolds for bone regeneration.” Materials 2.3 (2009): 790-832.