International Survey - Current Status

Tissue engineering research is a large and expanding activity across the globe. In the United States, the first government grants in this area were awarded in the mid-1980s. US Government funding had increased to around $10 million by 2000 and had reached $50 million by 2002. The majority of funding, however, has come from the private sector: $600 million in 2002 alone. Since 1995 it is estimated that over $4.4 billion has been spent on tissue engineering in the US. This has allowed the US to maintain a global lead in tissue engineering research, but the inbalance between private and public funding has brought its own set of problems to the industry.

Traditionally, the US has led the world in applied research, but has had a lesser emphasis on fundamental aspects. The recent failure of two major US-based tissue engineering enterprises led to a policy re-evaluation resulting in a realignment of research funding to more basic research. US research activities now more closely align with Europe and Asia (particularly Japan) where government funding is targeted to basic research with its intrinsic potential for developing novel intellectual property. Research in Europe is focussed largely on cell biology. Research in Japan is focussed on developing advanced biomaterials.

Europe and Asia place a strong emphasis on research into autologous cell therapies; where cells are removed from the patient, manipulated and returned to the patient. This is achieved as free cells (eg blood stem cell transplant) or with a supporting matrix (eg. bone, corneal transplant). To date the majority of studies in Europe have been based on the use of conventional biomaterials as supporting scaffolds for the expansion and implantation of autologous cells. In this situation, novelty arises from cellular rather than materials developments. However, the realisation that conventional biomaterials are often inherently unsuitable for many tissue engineering applications has recently spurred research into the molecular design of novel biomaterials.

Research in the US is aimed at developing autologous and allogeneic therapies for regenerative medicine.

  • Allogeneic therapies use donor tissue
  • Autologous therapies use the patient’s own tissue

The use of stem cells is a controversial area of research globally. Researchers in many countries, including Australia (through the National Stem Cell Centre) are investigating the technical challenges of this approach and the legal, cultural and ethical issues associated with using stem cells (especially embryonic cells). Until a consensus community viewpoint is reached, research is predominantly focused on the use of adult stem cells.

Virtually all tissue engineering applications require cells to be grown outside the body. Specialised bioreactors are used for this purpose. Considerable international research effort is aimed at developing bioreactors for two- and three-dimensional cell culture. Assuming the current problems of mass transport can be solved, enabling cells in the centre of a mass of tissue to survive, there remains the challenge of how this will occur following implantation. Similarly, the biomechanical requirements of engineered tissues is a poorly understood area across the globe, particularly in relation to how these properties change as a degradable scaffold is degraded and remodelled by cellular activity. The other side of this coin, the effect of mechanical forces on cell behaviour, is being studied by a number of groups across the world. Several groups are starting to explore the application of genomics to tissue engineering, whereby extensive databases are generated and the data then mined for specific purposes. To date this technology has largely been aimed at drug discovery, and the use of informatics in tissue engineering is still at a very early stage globally.

The current status of tissue engineering activities includes projects that are focused in key component areas of research such as:

Biomaterial Scaffolds

Some of the laboratories that are active in this area include:

Major questions being asked in this area include:

  • How can the physical and chemical properties of scaffolds be improved to:
    • enable cells attach to the scaffold?
    • provide growth factors and cytokines to stimulate the growth of new cells in the scaffold?
    • encourage blood vessels to grow (angiogenesis) and support the new tissue within the scaffold?
    • Prevent the body’s immune system rejecting the scaffold?

Clinical applications of Tissue Engineering

Some of the laboratories that are active in this area include:

Major questions being asked in this area include:

  • How can tissue engineering be applied to help repair or replace:
    • Skin? Clinical application: Engineered skin could improve the treatment of burns, diabetic foot ulcers, venous leg ulcers and improve reconstruction surgery (e.g. for patients suffering from cancer of the breast, head and neck)
    • Bone and Cartilage? Clinical application: Engineered bone and cartilage could improve the treatment of patients suffering from diseases of the bone and joints (e.g. osteoporosis, rheumatoid arthritis)
    • Blood vessels? Clinical application: Engineered blood vessels could improve the treatment of blocked blood vessels (e.g. for patients suffering from heart disease or stroke)
    • Nerves? Clinical application: Engineered nerves could improve the treatment of patients suffering from spinal cord injuries
    • Eye tissue? Clinical application: Engineered eye tissue (e.g. cells from the cornea or retina) could improve the treatment of patients suffering from loss of vision.

Cell Biology

Some of the laboratories active in this area include:

Major questions being asked in this area include:

  • How can tissue engineering improve our understanding of how cells:
    • Grow?
    • Differentiate?
    • Attach to scaffolds?
    • Release and respond to cytokines?
    • Move?
    • Die?
  • What types of cells offer the greatest promise for tissue engineering?
    • The recipient’s own cells (autologous cells)
    • Cells from another human (allogenic cells)
    • Cells from another species (xenogenic cells)

Social, ethical and legal aspects of Tissue Engineering

Some of the centres that are active in this area include:

Major questions being asked in this area include:

  • How should regulation of research in Tissue Engineering and clinical application of Tissue Engineering proceed?
  • What benefits and problems arise from commercialisation of research activities in Tissue Engineering?
  • To what degree does the public understand and support research and clinical practice in Tissue Engineering?
  • What are the ethical issues that arise in relation to the source of stem cells used in Tissue Engineering?
  • What are the ethical issues that emerge with Tissue Engineering, regenerative medicine and xenotransplantation?