Bone Grafts and Substitutes

Bone grafts may be divided into various subtypes based on source, structure or effects:

  • Autograft
  • Allograft
  • Synthetic products / substitutes
  • Bone stimulating agents – demineralised bone matrix (DBM), stem cells and Bone Morphogenic Protein (BMP)
  • Osteo-inductive
  • Osteo-conductive
  • Osteo-genic

Osteogenic:

  • Contains all precursors for bone growth – stem cells, osteoblasts, osteocytes and growth factors
  • Only example is autologous bone graft

Osteo-conductive:

  • Acts as a scaffold for bone growth
  • Includes agents such as calcium sulfate, hydroxyapatite, demineralised bone matrix, autologous bone graft. 

Osteo-inductive:

  • Materials which provide stimulation for growth of bone and production of bone-lineage cells from precursor stem cells
  • Includes demineralised bone matrix (DBM), bone morphogenic proteins (BMP’s) and autologous bone graft.

Autologous bone graft:

  • Gold standard for most bone-grafting purposes – osteogenic, osteoconductive, and osteoinductive.
  • May include vascularised grafts (eg fibula), cortical or cancellous grafts
  • Depending on the choice of graft type, may provide structural strength or space-filling effect. All will contain varying amounts of osteogenic properties with osteocytes, osteoblasts, osteoclasts, stem cells and BMP’s.
  • Cancellous bone graft provides overall maximal osteogenic capability due to it having the highest density of cells and BMP’s, and highest surface area of matrix interactions.
  • Associated with varying degrees of donor site morbidity and limitations of supply. Reamer-irrigator-aspirator (RIA) devices are associated with greater volumes of bone graft being harvested, of apparently higher quality in terms of stem cell and growth factor yield. RIA devices also appear to overall decrease the risk of complications compared to traditional iliac crest bone grafts (including pain, infection, fracture or vascular / abdominal / pelvic visceral injury), however are associated with their own complications (including iatrogenic fracture, cortical perforation, haemorrhage and heterotopic ossification).

Allograft:

  • Sourced from donor bone banks. These include fibula, rib, femoral head sources, and can include cortical, cancellous or cortico-cancellous structural products.
  • May be frozen, freeze-dried, irradiated or a mix of these. No cells should survive this process, hence no osteogenic properties. This processing also destroys BMP’s and 
  • Bone matrix / stroma remains, hence provides degree of structural integrity and osteoconductive effects. 

Calcium sulfate:

  • Eg: Stimulan, OsteoSet
  • Provides a rapidly-absorbable space-filler that can contain antibiotics, and thus provide long-release regional antibiotic coverage.
  • Absorbed over relatively short window (~6 weeks)
  • Can be associated with wound ooze, hypercalcaemia, heterotopic ossification

Demineralised Bone Matrix (DBM):

  • Eg: DBX Putty, Strand, Grafton
  • Provides a volume of material containing both collagen matrix (osteonductive) and growth factors (osteoinductive) properties. May absorb blood, marrow and tissue fluid to provide a void-filling effect.
  • Carrier materials such as those used in putties appear to have negative effects on formation of bone and successful fusion when used in the setting of spinal fusion (2).  Literature supporting the efficacy of DBM in trauma and other surgery is currently limited, and is often confounded by concurrent use of other materials (3).

Hydroxyapatite:

  • Hydroxyapatite (HA) provides a scaffold for bone growth (osteoconductive effect) and can provide structural support. Often used as a coating for uncemented prostheses in arthroplasty, to improve osseointegration (securing of implant to bone)
  • Currently appears to be limited evidence suggesting HA coating on otherwise equivalent stems reduces the chance of all-cause revision, but this varies with implant design (4).

Calcium triphosphate:

  • Eg: Accufill
  • Can be sourced as a paste which, after application, cures to a solid block of structural material in vivo. This provides an osteoconductive effect as well as structural reinforcement. It appears to provide long-lasting structural persistence in bone, while material that leaks into soft tissue can be rapidly removed by the body (5). This can allow for reinforcement of otherwise structurally insufficient bone, improving the load required for failure (6)

Bone Morphogenetic Proteins

  • Examples: Infuse Bone Graft
  • Bone morphogenetic proteins (BMP’s) are members of the TGF-b family of signalling proteins, and influence a wide variety of growth and differentiation pathways via serine-threonine kinase receptors. Effects in vivo include promoting formation of skeletal muscle, chondrocyte and osteoblast differentiation, along with various other organ development pathways. There are 16 classical BMP’s currently recognised, with BMP-1 being a matrix-metalloproteinase active on Type-1 collagen rather than a TGF-b molecule. (7) There are two BMP’s in clinical use, being BMP-2 and -7.
  • BMP-2: Stimulates both osteoblastic and osteoclastic differentiation and activation. Improves rate of successful spinal fusion, however is also associated with a variety of side-effects including ectopic bone formation, bone resorption and implant subsidence, seroma formation, inflammatory responses such as cervical spine swelling, and wound complications (8).
  • BMP-7: Stimulates osteoblastic differentiation from mesenchymal stem cells. When used for long-bone non-unions, it is associated with equivalent rates of union as autologous bone grafts with a lower rate of complications. (9)

References

  1. Wang, Wenhao, and Kelvin W K Yeung. “Bone grafts and biomaterials substitutes for bone defect repair: A review.” Bioactive materials vol. 2,4 224-247. 7 Jun. 2017
  2. In-vivo Performance of Seven Commercially Available Demineralized Bone Matrix Fiber and Putty Products in a Rat Posterolateral Fusion Model; N Russell et al, Front Surg. 20 Mar 2020;7:10 https://pubmed.ncbi.nlm.nih.gov/32266283/
  3. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery – A systematic review; J. van der Stok, et al, Bone Joint Res. Jul 2017; 6(7): 423–432.
  4. What Is the Risk of Revision Surgery in Hydroxyapatite-coated Femoral Hip Stems? Findings From a Large National Registry, M C Inacio et al, Clin Orthop Relat Res, Dec 2018;476(12):2353-2366
  5. Calcium Phosphate paste for Bone Defect in Total Knee Arthroplasty, Orthopaedic Proceedings, Vol. 86-B, No. Supplement 4, T. Sato, et al
  6. Calcium Phosphate Bone Void Filler Increases Threaded Suture Anchor Pullout Strength: A Biomechanical Study; Arthroscopy: The Journal of Arthroscopic & Related Surgery, 36-4, 2020, 1000-1008, M.A. Diaz et al
  7. Bone Morphogenetic Proteins; Katagiri, T, Tetsuro, W, Cold Spring Harbor perspectives in biology vol. 8,6 a021899. 1 Jun. 2016
  8. A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2; James, AW et al. Tissue engineering. Part B, Reviews vol. 22,4 (2016): 284-97
  9. Bone morphogenetic protein-7: Review of signalling and efficacy in fracture healing, Cecchi S,Bennet SJ, Arora M, Journal of Orthopaedic Translation, 4, 2016, 28-34

Author Contributions

Sean Griffiths, WH Registrar, 2020