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. Level I studies document superiority to autograft for support of subchondral bone defects in tibial plateau fractures and other articular injuries.
iv. Composite grafts available such as BMAC combined with scaffolding properties of TCP to stimulate cell proliferation and differentiation.
C. Demineralized bone matrix (DBM), allogenic bone:
1. Formed by acid extraction of the mineralized ECM of allograft bone.
2. Contains type-1 collagen, noncollagenous proteins, osteoinductive growth factors including bone morphogenetic proteins (BMPs) and other inductive factors.
a. Effectiveness of autogenous BMPs in the DBM is in question.
i. Differences in the growth factor concentrations between individual products.
ii. Potencies of each available growth factor within each product is variable.
b. DBM is available as freeze-dried powder, granules, gel, putty, strips, or in combination with allogeneic bone chips or calcium sulfate granules.
c. Sterile processing and carrier molecules influence effectiveness of these materials.
3. DBM is highly osteoconductive due to its particulate/porous nature/increased surface area.
4. Preclinical data documents DBM forming de novo bone in lesser animal models.
5. Human data is limited to isolated case reports and uncontrolled retrospective reviews.
6. Effectiveness of DBM as a stand-alone graft is equivocal and not recommended.
7. Best evidence suggests comparable efficacy when combined with autograft compared to autograft alone. Use DBM as graft extender.
D. Bone morphogenic proteins (BMPs)—true “osteoinducers.” Factors stimulate circulating undifferentiated mesenchymal cells changing them directly into osteoprogenitor cells.
1. Mode of action
a. BMPs bind at specific cell surface receptors TGF-β ligands.
b. Protein complexes (intracellular messengers) form to trigger downstream molecular signals and transmit them to the nucleus. SMADs are intracellular proteins that transduce extracellular signals from surface ligands to the nucleus. Gene transcription is activated to modulate cell function.
c. BMPs direct conversion of cells into a bone-forming lineage.
2. Rh-BMP-2, Infuse, is approved for use for augmentation of an interbody fusion device during an anterior lumbar interbody fusion (ALIF) or oblique lateral interbody fusion (OLIF) procedures. Single level involvement. Rh-BMP-2 is approved for use within 10 days for open tibia fractures treated with an intramedullary (IM) nail. It is the graft substitute applied to defects at the time of delayed closure.
3. Level 1 data demonstrating efficacy equal to that of autogenous bone graft.
a. Complications of use in lumbar spine surgery include heterotopic ossification (HO), graft osteolysis, increased infection, arachnoiditis, increased neurological deficits, and retrograde ejaculation.
b. Complications in cervical spine fusion include tracheal edema with air restriction.
c. Heterotopic ossification is the most common complication for trauma-related conditions.
E. Extracellular matrices (ECM)
1. Tissue-derived (bovine intestine, porcine bladder, etc.) scaffolds contain native collagens, glycosaminoglycans, and growth factors.
a. ECM have an intact epithelial basement membrane layer, and are available as micronized powder and lyophilized sheets.
b. This biologic scaffold presents a tremendous surface area for attachment of fibroblasts for the deposition and substitution with collagen.
c. ECM degradation peptides are chemoattractive to appropriate progenitor cells, for constructive remodeling response and multilayer tissue regeneration.
d. ECM have also