Understanding the biology of bone grafts: from the origin until today

The study of bone graft biology is a fascinating concept and one which has been preoccupying medical practitioners for thousands of years.

A little bit of history

Even before the Old Testament was written, there is solid evidence to suggest that prehistoric ‘surgeons’ were placing animal bone into human skulls to great effect. When two ancient skulls were discovered near Lake Sevan in Armenia, they showed that animal bone had been used to repair 7mm and 2.5mm defects respectively. Moreover, scientists know that they survived because both skulls showed evidence of bone regrowth around the implanted area. Incidentally, the people who inhabited the area at that time and performed this technique – the Khurits- lived some 4000 years ago.

The first Xenograft

However, it wasn’t until the 1600s, when a Dutch surgeon called Job Van Meekeren successfully implanted bone from a dog into the skull of a wounded soldier, that the Xenograft technique became recognized. In 1821, the first recorded autogenous grafting procedure was recorded (the grafting of bone from one part of the body to another) and in 1879, Sir William MacEwen successfully replaced part of a boy’s humerus with bone taken from other donors (allografting).

Understanding the biology of bone grafts

Yet, despite 4000 years in the making, it’s only really in the past two decades that scientists have begun to show a fundamental understanding of bone graft biology. Prior to this, it could be said that grafting bone successfully was akin to building a complex piece of flat-pack furniture without any instructions. While the constructor may have got there in the end, chances are, that it was more luck than judgment.
Over time, however, as more knowledge was gained, a comprehensive understanding of how bone grafting works at both cellular and molecular levels allowed scientists to write their own instructions or blueprints for success. Insights into osteoinduction – The process by which Mesenchymal Stem Cells (MSC’s) are used to make chondroblasts and osteoblasts, and osteoconduction – the process of how capillaries and tissue are implanted onto a host scaffold – were key breakthrough moments.

The Golden Age of bone grafts

On the back of this initial success, grafting techniques became very much in demand.
In fact, after blood, bone is now the most commonly transplanted human item in the world today, resulting in over 2 million grafts per year! It’s used in every aspect of reconstruction from building jaw bone mass to aid implant-based restorations, through to complex spinal reconstructions.

Limitations of both alografts and autografts

That said, even with the extensive knowledge that we have of bone grafting procedures, both autograft and allograft techniques (the most commonly used types of bone graft) are impractical long-term solutions. Factors that make it so include:

  • The problem of donor site morbidity – that is the additional functional restrictions a patient has to go through when harvesting bone from one part of the body and transplanting to another
  • The issue of obtaining sufficient quantities of bone that are fit for the purpose
  • The need for time-consuming and meticulous donor screening and bone processing
  • The possibility of a systemic and local disease using allografted bone, and
  • The complex nature of genetic factors

Complications associated with the placement of a graft

Unfortunately, the human body is somewhat ‘picky’ and complications can abound when it discovers what is essentially a foreign object, invading it. This can lead to infections or defective transplants after surgeries. Therefore, as it stands, clinicians need to take into account a large checklist of factors including:

  • The type of bone graft used – Autografts, Allografts, etc…
  • The location of the implantation site
  • The presence of veins in and around the graft and the host-graft interface
  • The relationship of genetics between the donor and host
  • Out-of-body graft preservation techniques and…
  • The presence of systemic factors that may perpetuate disease

This is before any particular type of grafting of this nature can be considered. Clearly, this isn’t ideal particularly in those patients awaiting critical or time-sensitive bone reconstructions. Furthermore, the demand for bone grafting is becoming higher as the population ages. As such, these dilemmas have forced experts into exploring other – and arguably better – options. In other words, bone grafting techniques and the understanding of bone graft biology are having to evolve!

The present and future of bone grafting as we know it!

Use of biological devices

One of the most interesting developments in bone graft research is the emergence of biological devices to augment bone grafts. Recombinant Human Growth Factors or (RHGF’s) allow patients to grow their own bone. Given the right environmental conditions, some stem cells, and a fat sample, it’s now possible for perfect-match bone to be grown in as little as 3 weeks. As it’s derived from the patient’s own stem cells, it’s something that the patient’s body hopefully won’t reject. Clinical trials are ongoing, but the results appear to be promising.

3D printing of bone

Of course, the other advancement in bone graft biology and one that we at Mimetis Biomaterials are particularly proud to be involved in, is 3D printing. Synthetic bone can now be printed using three-dimensional printing technology that not only matches the anatomical shape of a patient’s defects but can quickly lead new bone regeneration and growth. So that’s where we are now! In a few years’ time, however, wouldn’t it be great if painful, invasive and often problematic bone transplants, became a thing of the past? There’s no doubting that with the knowledge in bone graft biology that we currently have and the advancements in technology to match, we’re well on the way to achieving just that.

The Biology of Bone Grafting
Journal of the American Academy of Orthopaedic Surgeons

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