for Clinical Use
A. Autogenous cellular materials (osteogenic) (▶Table 8.1).
1. Autogenous iliac crest bone graft (AICBG, gold standard)—other sites include posterior iliac crest, proximal tibia, distal femur, calcaneus, and distal radius. Rapid revascularization occurs and performs best in well-vascularized beds.
a. Approximately 30 mL of graft reliably harvested from an anterior iliac crest.
b. Complications related to the harvest and limited availability.
2. Reamer Irrigator Aspirator (RIA; Synthes, Paoli, PA)—the medullary canal of the femur or tibia is reamed with a collection device and delivers 30 to 90 mL for grafting.
a. Elevated osteoinductive growth factors, osteoprogenitor/endothelial progenitor cell types are used compared to AICBG.
b. Cell viability and osteogenic potential is equal in both RIA and AICBG.
3. Bone marrow aspirate concentrate (BMAC; ▶Fig. 8.5).
a. BMAC has a high concentration of viable connective tissue progenitors for grafting.
b. Bone formation is dependent on the number of cells available in the graft.
i. Technologies include methods for harvest and concentration of bone-forming cells.
ii. Implanted BMAC combined with bioactive scaffold matrix allow differentiation into an osteoblastic cell lineage for bone repair.
iii. Allogeneic human undifferentiated mesenchymal “stem cell grafts” from cadaver donors are clinically available. There is limited clinical data available for these, therefore use with caution.
4. Platelet concentrates (PC)—platelet activation following injury or surgical insult. Platelets release protein content (degranulation) of more than 30 bioactive proteins. Primary factors include PDGF and TGF-β.
a. The PDGF
i. Primary function of PDGF is to stimulate cellular replication (mitogenesis).
ii. It increases cell populations of mesenchymal stem cells and osteoprogenitor cells.
iii. It also activates macrophages resulting in debridement of the surgical or traumatic site.
b. Transforming growth factor β (TGF-β)
i. It stimulates proliferation of osteoblast precursor cells and collagen.
ii. Increases osteoblast cell line, and the upregulation of osteoblasts.
Fig. 8.5 (a, b) The aspiration technique is very specific in order to maximize the number of effective progenitor cells per unit. No more than 2 mL should be aspirated from any given area to avoid dilution with peripheral blood. The concentrate is then loaded onto a conductive substrate for implantation (composite grafting).
c. PC stimulate the formation of blood vessels by invasion of pluripotential mesenchymal stem cells, monocytes, and macrophages. PC factors direct chemotactic and mitogenic effects on osteoblasts and osteoblast precursors.
d. Level I evidence is lacking to indicate PC, alone or in combination, has a substantial effect on rates of bone healing.
i. PC may have a positive effect as an adjunct to local bone graft.
ii. Soft tissue effects: published series for clinical trials covering eight clinical conditions, such as rotator cuff, tennis elbow, with PC augmentation. Insufficient evidence to support PRP for musculoskeletal soft-tissue injuries.
e. PC may have beneficial effects for knees with early degenerative changes.
5. Recombinant PDGF (rh-PDGF) plus calcium phosphate matrix (rhPDGF/TCP) is an alternative to autogenous bone graft (Augment). Rh-PDGF is efficacious for diabetic fracture treatment and approved for defect management for foot and ankle indications.
B. Osteoconductive substrates with porous structures mimics cancellous architecture.
1. Facilitate migration, attachment, and proliferation of mesenchymal stem cells.
2. Calcium ceramics are the primary type of conductive materials.
a. Calcium sulfate substitutes
i. Calcium sulfate is minimally porous.
ii. Rapid degradation by chemical process with loss of compressive strength.
iii. Current best use is as carrier for adjuvant antibiotics. Material properties are advantageous for delivering high-dose antibiotics to infected defects.
b. Calcium phosphate substitutes (▶Fig. 8.6).
i. Available in a variety of delivery forms such as solids, powders, and cements.
ii. Slow degradation by biological process with maintained compressive strength.
iii. Highly crystalline structures with variable porosity and rates of osteointegration based on crystalline structure and pore size.
Fig. 8.6 (a, b) Computed tomography scan of plateau fracture demonstrating subchondral defect. (c) Elevated joint surface supported with particulate and injectable CaPO4 conductive substrate. (d) 1-month post surgery with material present and maintenance of reduction. (e) 4-months post surgery with incorporation of graft substitute and articular surface maintained. (f) 10 months post surgery with nearly all material osteointegrated and articular surface well maintained.
c. Hydroxyapatite
i. Crystalline structure dictates the rate of osteointegration. Materials integrate via a cell-mediated response and pore structure allows for cellular attachment.
ii. Prolonged osteointegration because of the paucity of cellular interactions. High compressive strength.
iii. Brittle mechanics and slow bone formation, hydroxyapatite alone is not commonly used as a conductive bone substitute nowadays.
d. Tricalcium phosphate (TCP)
i. Less brittle and faster resorption due to increased porosity.
ii. Also delivered in an injectable form. Timing of fracture fixation hardware is material dependent.
iii.
