Bone Regeneration: Current Practice

I remember speaking to a man who came for orthopaedic surgery on a fractured left leg. This was because of a traffic collision that happened four years ago. For all these years, he had been living with a dynamic external fixator. I discovered that this cumbersome metal scaffolding supports new bone formation to heal the fracture.

It made me think about how bones have an intrinsic ability to regenerate through an incredibly complex physiological process of cells and bio signalling pathways. Unsurprisingly, a lot can go wrong.

You can get avascular necrosis, a condition where the bone tissue dies due to a lack of blood supply. You can also suffer from osteoporosis, a disease that weakens the bones of people, making them likely to break. The physical trauma, surgeries to remove tumours, or infections from surgeries can also cause large bone defects.

Therefore, to treat these injuries successfully, we need to facilitate the healing process. How do dentists and orthopaedics – the field of surgery focusing on muscles and the skeleton – treat bone fractures and defects?

Bone grafting

Bone grafting is a surgical procedure that replaces missing bone with transplanted bone. It can be an autologous bone graft or an allograft.

Autologous bone grafting is when the transplanted bone is from the individual that is receiving the graft, typically using bone from their pelvis. Using bone from the same body prevents the patient’s immune system from attacking the transplanted bone, which is a common problem in organ transplants.

But it’s not without its own problems. Patients must undergo an additional risky surgical procedure to harvest the bone which will be transplanted.¹ Problems can also develop overtime if the transplant is continued inflammation which prevents the graft from healing. The implanted graft can also be resorbed, meaning the transplanted bone is broken down by the body.

In contrast, allografts harvest bone from a source that isn’t the patient. This can either be from human cadavers or live donors. Allografts have the issues that autologous bone grafts avoid. As the transplanted bone isn’t from the patient’s body, an immune response is likely. The immune system will know the bone isn’t from their body and, believing it be a potential pathogen, attack it as an invader.

Despite this, the procedure is common due to the graft not having a size limit. This allows for many different types of grafts to treat a range of different injuries. They also have a shorter operation time and, cosmetically, they produce better outcomes.²

Mechanical stimulation on bone regeneration

This involves using fixation devices, which can be internal or external, for large fractures. They stabilise the fracture, keeping the fractured ends in line with each other to ensure they join as they heal.

These devices adjust shear stress to change the healing process. A high shear stress will encourage connective tissue to form around the bone; a low shear stress will stimulate bone and cartilage formation.³ They also help to create new blood vessels for the healing bones.

Internal fixatives are rods surgically screwed onto the bone inside the body. The rod can either be screwed inside the fractured bone or onto a plate just outside of the bone, but still inside the body.⁶ Asides from the gruesome image of such an operation, the surgery required creates the same risks that bone grafting does.⁷

External fixatives involve drilling holes into the fractured body part where bolts are slotted into. These bolts are attached to rods outside of the body which are supported by a frame, like scaffolding at a construction site. They are only used when internal fixation is too dangerous, for example in open fractures.

An example of an external fixation device is the dynamic external fixator I mentioned at the beginning. It gradually pulls the two sides of the fractured bone apart to facilitate the growth of new bone into the small gap.

External fixators have some benefits over internal fixators. As the surgery is less invasive, it reduces the chance of infection and being external, the stress it provides is easier to adjust. However, the bulky frame can be very inconvenient, and needs more maintenance than internal fixators.⁸

Growth factor therapy

These are molecules like bone morphogenetic proteins (BMP), which triggers the development of osteoblasts, a specialised stem cell needed to synthesise new bone. They are popular, with BMPs being approved by the FDA in 2001 to treat large bone defects.

However, these growth factor molecules are sensitive to the heat and acidity of the body. Consequently, they become unstable upon entering the body, and can disintegrate at the site of injury before successfully healing the bone.

Scientists have tried to solve this problem by attaching them to other compounds. These protect the growth factor as it travels around the body.⁴ Even with this solution, they’re very expensive, and if the drugs aren’t on-target, they can stimulate bone growth in unwanted areas.

The future

Despite the advances that medicine has made, it’s clear that we need better treatments. As the man who had a fixator on this leg for four years shows, there are still problems and limitations to the tools we currently have that support bone regeneration.

In my next article, we’ll look at what science holds for the future of bone regeneration.

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Diluksha Prasad Jayawardana is a final year medical student at the University of Colombo, Sri Lanka. He specialises in orthopaedic surgery.

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References

1.St John TA, Vaccaro AR, Sah AP, Schaefer M, Berta SC, Albert T, et al. Physical and monetary costs associated with autogenous bone graft harvesting. American journal of orthopedics (Belle Mead, N.J.). 2003;32(1):18-23. https://pubmed.ncbi.nlm.nih.gov/12580346/

2. Izzo, Cassandra M., “Choosing an allograft or autograft in orthopedic surgeries for athletes” (2016). Honors Theses and Capstones. 304. https://scholars.unh.edu/honors/304

3. Lacroix D, Prendergast PJ. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. Journal of Biomechanics .2002;35(9):1163–1171.

DOI: 10.1016/S0021-9290(02)00086-6

4. Yun YR, Jang JH, Jeon E, Kang W, Lee S, Won JE, et al. Administration of growth factors for bone regeneration. Regenerative medicine. 2012;7(3):369-85. DOI: 10.2217/rme.12.1.

5.Laschke MW, Witt K, Pohlemann T, Menger MD. Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization. Journal of biomedical materials research. Part B, Applied biomaterials. 2007;82(2):494-505. DOI: 10.1002/jbm.b.30755.

6. https://medlineplus.gov/ency/imagepages/18023.htm

7. https://smgortho.com/procedure/insertion-of-plates-screws-or-rods/ 8. https://smgortho.com/procedure/external-fixators/