Biotechnology has undergone massive technological and scientific advances in the last decades.

However, Mankind has been using biomaterials since ancient times, such as natural tissues (from plant and animal origin), to heal wounds and lesions from hunting or exploration. The materials used by man for this purpose have been changing over centuries, becoming more and more effective, until synthetic polymers, metals, ceramics, and composites became a reality. Tissue engineering is a recent scientific area and is based on the development and manipulation of artificial implants, laboratory-created tissue, or living cells that can replace or stimulate injured and damaged areas in our bodies.

What is a biomaterial?

A biomaterial must meet several requirements in order to be considered compatible for use on human bodies:

• Biocompatibility, to avoid rejection by the human organism;
• Sterility, in order to avoid infection;
• Osteoconductivity, to promote cellular adhesion and bone growth;
• Biodegradability, for an easy integration in the organism;
• Mechanical properties compatible with its purpose function;
• Non-toxicity;
• Possibility of large-scale processing;
• Similar density to biologic environments.

Is bone regeneration possible via Tissue Engineering?

Bone tissue is a dynamic and very vascularised tissue that grows, renews itself and lives throughout the organism’s whole lifespan, and which main functions are to support the body and enable mobility.
When an orthopaedic lesion happens, and because of the bone tissue’s regenerative ability, both conservative therapies and surgical techniques can be applied with the aim of healing the lesion. Sometimes, however, it is necessary to resort to bone grafting and bone replacement, especially in the case of extensive lesions resulting from trauma, surgical procedures, and congenital bone deformities.
Although tissue transplants are widely used (bone grafts and replacement), this technique brings forward some limitations, namely the possibility of graft rejection in addition to a high risk of infections. Tissue Engineering can mitigate these limitations, making it a promising alternative in bone replacement, in the case of orthopaedic irregularities, bone tumours, arthrosis treatment, spinal segmental stabilisation, or orthopaedic and reconstructive surgery.

How does Tissue Engineering work?

The entire process is based in the development of new functional tissue, using living cells combined with support structures – scaffolds – that provide a structure to the growing tissue. These scaffolds are developed to present ideal characteristics in terms of biocompatibility, biodegradability, mechanical endurance, and adequate environment for cellular adhesion, proliferation, and survival, being an excellent strategy to increase bone healing and regeneration. To stimulate and improve cellular growth, precursor cells and growth factors are added to scaffolds which in turn are connected to an adequate vascularisation that allows the access to the nutrients and oxygen required for a healthy growth and differentiation of these new tissues.

What materials are more used in Tissue Engineering?

The process of development of biomaterial technology has been hand in hand with medical research in the microenvironments of orthopaedic lesions. As such, considering the changes in requirements and desired characteristics for a determined material, three generation of biomaterials were created:

First generation: bioinert materials
Bioinert materials arose in the mid-60’s and 70’s, with the main goal of being used in medical implants. Its function was to achieve properties (physiological and mechanical) similar to the damaged tissue without causing harmful interactions with the host organism – in other words, while being biologically inert. Examples of materials belonging to this generation are metals (stainless steel and titanium), ceramic materials (alumina and zirconia) and polymers (propylene and polymethacrylate). As the years wore on, it was found that these materials caused the formation of a layer of fibrous tissue around it, what would hinder the adhesion of the implant to the receiving tissue and consequently cause its detachment. This would, of course, make its use non-viable.

Second generation: bioactive and biodegradable
The advance in biotechnology allowed to improve the bioinert response of first-gen materials and achieve a specific biological action, which would impede the formation of the fibrous layer, thus improving the adhesion to the receptor tissue. Examples of second-generation biomaterials include bioactive glass, bioactive ceramics, bioactive glass-ceramics and composites. Biodegradable biomaterials include synthetic polymers (poly-ɛ-caprolactone, or polylactic acid) or others considered natural, like chitosan and hyaluronic acid.

Third generation: biomimetic materials
These materials were conceived to drive specific cellular responses on a molecular level, reconciling the bioactivity and biodegradability of the previous generation, with the ability stimulation of specific cellular procedures and activities – especially in the development of porous matrices made of biomimetic materials. Tissue engineering focuses on the development and research of such materials and one of its biggest advantages is the achievement of mechanical characteristics that are suitable and compatible with the organism tissue, as well as properties that are similar to the patient’s native bone extracellular matrix.