The Biologic Response to Orthopaedic Implants

OPBSPathologyBiomaterials

Must Know

• Permanent implants must be efficacious, safe and cost-effective.
• Biocompatibility means performing the intended function without undesirable local or systemic effects, with the right host response.
• Every operation triggers acute inflammation, led by neutrophils (PMNs) and macrophages.
• Unresolved acute inflammation leads to fibrosis or chronic inflammation.
• Granulomatous inflammation is chronic inflammation dominated by epithelioid activated macrophages.

More on inflammatory mediators

• Surgical injury releases TNF, IL-1, chemokines such as IL-8 and MCP, nitric oxide and peroxide metabolites.
• Chronic inflammation shows PMNs, macrophages, giant cells, lymphocytes and plasma cells with fibrosis and angiogenesis.

Granuloma	Basis	Lymphocytes	Implant trigger
Foreign body	Nonantigenic, nonspecific	Few	Polyethylene and PMMA particles
Immune	Antigen driven	Many	Cobalt chrome byproducts in some patients, with more necrosis

Cemented and Uncemented Interfaces

• Uncemented fixation aims for osseointegration through press fit, roughening, porous or bioactive coating.
• Micromotion beyond about 50 µm produces fibrous tissue instead of bone.
• Optimal pore size for porous coatings is about 100 to 400 µm.
• Bone ingrowth mirrors primary fracture healing, with woven bone formed by intramembranous ossification.
• Instability, a large gap, poor vascularity or infection produce fibrous or inflammatory membranes.

More on interface histology

• Charnley saw cell damage within 500 µm of cement weeks after surgery from chemical, thermal and mechanical injury.
• Well-fixed cemented stems show close bone cement contact and a trabecular neocortex around the mantle.
• Giant cell reaction is rare at well-fixed cemented femoral interfaces.
• Cemented cups develop a progressive centripetal foreign body reaction to polyethylene and cement particles.
• Ingrowth is greater at the end of porous coating, next to screws and where intimate fit meets compressive load.
• Smooth surfaces, infection and excess motion reduce ingrowth.
• Unfilled screw holes with fibrous tissue let particles reach cancellous bone.
• Ingrown or hydroxyapatite coated surfaces block particle migration. One study found more acetabular loosening with hydroxyapatite.
• Highly porous tantalum and titanium mimic cancellous bone, have higher friction and can replace bulk allograft.
• Autopsy retrievals of working implants avoid the bias of revision specimens.
• Harris found little fibrous tissue around well-fixed cemented stems up to 17 years.

Loose Implants and Osteolysis

• Loose cemented implants show radiolucent lines, migration and a fibro-inflammatory membrane up to several mm thick.
• The membrane holds fibroblasts, macrophages, giant cells and vessels with scant lymphocytes and PMNs.
• Polyethylene shards are birefringent under polarised light and stain with Oil Red O.
• Most debris measures 0.3 to 5 µm, though needle shards can reach 1 mm.
• Osteoclasts line the membrane where scalloped resorption occurs. New bone formation is also prominent.
• Osteolysis is accelerated resorption plus depressed formation driven by wear particles.
• Joint fluid pressure pumps debris far from its source. Particles reach lymph nodes, liver and spleen.
• Particle-activated cells release PGE2, TNFα, IL-1β, IL-6, IL-8, chemokines, nitric oxide and peroxides.
• NFκB is the main transcription factor regulating these cytokines.
• Osteoblasts and stromal cells release RANKL, which binds RANK on osteoclast precursors.
• Osteoprotegerin is a soluble decoy receptor that blocks RANKL.

More on osteolysis detail and experimental treatments

• Loose uncemented implants have a thinner fibrous layer.
• Aggressive granulomatosis may reflect uncoupling of macrophage clearance from fibroblast matrix repair.
• Strategies under study block macrophage recruitment (mutant MCP-1, 7ND), switch macrophages to anti-inflammatory with IL-4, or inhibit NFκB.
• All have worked in vitro and in small animals only.
• Fluid pressure, mechanical factors and low grade infection may also contribute.

Bearing Surfaces

Bearing	Debris	Biological response
Metal on polyethylene	Polymeric, micron sized	Nonspecific foreign body granuloma
Highly cross-linked polyethylene	Far fewer, slightly smaller particles	Lower particle burden outweighs any added reactivity
Ceramic on ceramic	Very few, mostly nanometre	Similar biological potential to polyethylene
Metal on metal	Many particles 10 to 50 nm, plus Co and Cr ions	Type IV hypersensitivity, immune granuloma, pseudotumour

• MOM wear is low because small clearance gives thin film lubrication and the surfaces self-polish.
• MOM ions appear in blood, erythrocytes, serum and urine. Cancer link seen in animals, not humans.
• Soluble metal byproducts bind serum proteins as haptens, driving adaptive immune reactions.
• Commonest metal sensitisers are nickel, cobalt and chromium. Titanium, vanadium and tantalum rarely sensitise.
• Pseudotumours are granulomatous masses with macrophages, T cells, plasma cells and widespread necrosis.
• Pseudotumour risk factors are young women, small components, dysplasia, malposition, edge loading and impingement.
• Pseudotumour cases should be revised early to a non-MOM bearing.

More on bearing detail

• Higher carbon alloys wear better in MOM bearings.
• MOM histology shows perivascular T and B lymphocytes, plasma cells, fibrin, necrosis and eosinophils.
• MOM resurfacing and THA have higher early and intermediate revision rates than polyethylene bearings.
• Ceramic debris rises with surface damage, loss of lubrication, stripe wear, impingement, edge loading, chipping and fracture.
• Willert described 19 MOM hips with early pain and effusion. Lymphocyte transformation tests were positive in 10 of 16.
• CrPO4 corrosion products can provoke immune reactions and act as third bodies.
• Revision of pseudotumour finds more soft tissue and bone necrosis than expected, with poor outcomes.
• Switching to ceramic heads on cross-linked polyethylene to avoid trunnionosis has limited evidence.
• Highly cross-linked polyethylene wears well in vivo to 10 to 15 years.

Stress Shielding

• Stiff cobalt chrome uncemented stems bypassed proximal load, causing proximal femoral atrophy by Wolff law.
• Bone hypertrophies near the distal stem, especially at the end of porous coating.
• Larger, longer, stiffer stems cause more stress shielding than short narrow ones.
• Full length porous coating adds to stress shielding.
• Stress shielding has not been linked to clinical stem failure but threatens revision bone stock.
• Remedies include proximal fit and fill, tapered or slotted designs and lower modulus titanium or composite stems.

Carcinogenesis

• Prolonged high Co, Cr and Ni levels caused sarcoma and lymphoma in rodents.
• Stainless steel devices have caused sarcoma in dogs and cats.
• Visuri reviewed 46 malignancies at THA sites, mostly sarcomas, with malignant fibrous histiocytoma commonest in soft tissue.
• Mean latency was 6 years. 77 percent died within 1 year.
• No direct link between metal implants and human cancer has been established.

More on cancer background

• Bulk polymers and ceramics have few biological effects. Their particles cause nonspecific chronic inflammation.
• Metal protein complexes can act as antigenic haptens.

Fracture Fixation Implants

• Reaming destroys endosteal supply, reduces cortical flow and raises muscle and soft tissue flow.
• Endosteal supply recovers in about 12 weeks in large animals.
• Reaming deposits osteogenic marrow locally but can embolise marrow, depending on reamer design and canal pressure.

Bioabsorbable implant (Böstman, 2528 cases)	Polyglycolic acid	Polylactic acid
Significant foreign body reaction	5.3 percent	0.2 percent (one case)
Onset	2 to 3 months	4.3 years
Degradation	Faster	Slower, hydrophobic

• Across all 2528 cases the reaction rate was 4.3 percent, presenting as a painful fluctuant papule or discharging sinus.
• 57 percent of reactions had local osteolysis.
• Screws and serrated bolts reacted more than pins and rods because of greater surface area.

More on plates and bioabsorbables

• Full contact plates by wide exposure disturb blood supply and cause adverse remodelling.
• Newer limited contact plates, periosteal preservation and bridging fixation protect soft tissue and blood supply.
• Quinone dye and poorly vascularised sites increased risk.

Imaging and Surface Modification

• Radiographic loosening signs are migration, progressive circumferential lucency, cement mantle fracture and implant fracture.
• Progressive halos around screws or pins mean lost fixation or infection.
• CT gives finer sections but uses ionising radiation and suffers metal beam hardening.
• Metal artefact suppression MRI shows bone oedema, synovitis, collections, sinus tracts and loosening without radiation.

More on surface modification

• Ultrasound screens for masses and fluid. Nuclear imaging helps difficult infection cases.
• Calcium phosphate and bisphosphonate coatings work experimentally but have little clinical translation.
• Etching, blasting, plasma spray, porous coatings and nanopatterning alter topography. Batch reproducibility limits translation.
• Fluoride, strontium, zinc and silver have been added to calcium phosphate coatings.
• Biomolecular coatings (RGD, collagen mimetics, BMP-2, SDF-1, DNA) remain preclinical.
• Absorbable magnesium strontium alloys degrade fast. Microarc oxidation calcium phosphate coating improves corrosion resistance in vitro.

Numbers to Remember

• Micromotion limit. About 50 µm.
• Pore size. 100 to 400 µm.
• Cement injury zone. 500 µm.
• Polyethylene debris. Mostly 0.3 to 5 µm.
• MOM particles. 10 to 50 nm.
• Endosteal recovery. About 12 weeks.
• PGA versus PLA reaction. 5.3 percent versus 0.2 percent, 2 to 3 months versus 4.3 years.
• THA survivorship. Over 90 percent at 15 years for good designs.

Memory Aids

• Plastic is foreign, metal is immune. Polyethylene and PMMA give foreign body granulomas. Cobalt chrome can give immune granulomas.
• RANKL revs, OPG obstructs. RANKL drives osteoclasts. OPG is the decoy that blocks it.
• Glycolic goes quick. PGA degrades and reacts sooner than PLA.

Exam Traps

• The membrane around loose metal on polyethylene implants has few lymphocytes.
• MOM reactions are type IV delayed hypersensitivity.
• Titanium and tantalum rarely sensitise.
• Highly cross-linked polyethylene particles are slightly smaller but far fewer.
• Reaming lowers cortical blood flow but raises surrounding muscle flow.

Related pages. Bearing Surfaces and Wear, Metals, Bone Cement (Polymethylmethacrylate), Material Properties

Source

Goodman SB. The Biologic Response to Orthopaedic Implants. In. Aaron RK, editor. Orthopaedic Basic Science. Foundations of Clinical Practice. 5th ed. Philadelphia, Wolters Kluwer, 2021.

Practise Type X questions on this topic

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 17 October 2026.