From benchtop to clinic: a translational analysis of the immune response to submicron topography and its relevance to bone healing.

Proper regulation of the innate immune response to bone biomaterials after implantation is pivotal for successful bone healing. Pro-inflammatory M1 and anti-inflammatory M2 macrophages are known to have an important role in regulating the healing response to biomaterials. Materials with defined structural and topographical features have recently been found to favourably modulate the innate immune response, leading to improved healing outcomes. Calcium phosphate bone grafts with submicron-sized needle-shaped surface features have been shown to trigger a pro-healing response through upregulation of M2 polarised macrophages, leading to accelerated and enhanced bone regeneration. The present review describes the recent research on these and other materials, all the way from benchtop to the clinic, including in vitro and in vivo fundamental studies, evaluation in clinically relevant spinal fusion models and clinical validation in a case series of 77 patients with posterolateral and/or interbody fusion in the lumbar and cervical spine. This research demonstrates the feasibility of enhancing biomaterial-directed bone formation by modulating the innate immune response through topographic surface features.

Accelerated bone formation by biphasic calcium phosphate with a novel sub-micron surface topography.

Osteoinductive calcium phosphate (CaP) bone grafts have equivalent performance to autografts in repairing critical-size bone defects. The osteoinductive potential of CaP is linked to the size of the surface topographical features. In the present study, two novel biphasic calcium phosphate (BCP) bone grafts were synthesised with either sub-micron- (BCP<µm) or micron-scale (BCPµm) needle-shaped surface topography and compared to dimensionally similar tricalcium phosphate (TCP) with grain-shaped surface structures (TCP<µm and TCPµm). To clarify the possible function of the surface morphology (needle-like vs. grain-like) in initiating bone formation, the four CaP test materials were physicochemically characterised and implanted for 12 weeks in the dorsal muscle of beagles. The sub-micron needle-shaped topography of BCP<µm triggered earlier bone formation (3-6 weeks) as compared to the grain-shaped surface topography of TCP<µm, which formed bone at 6-9 weeks. After 12 weeks, the amount of induced bone formation in both materials was equivalent, based on histomorphometry. The micron-sized needle-shaped surface topography of BCPµm led to limited formation of new bone tissue, whereas its counterpart, TCPµm with grain-shaped surface topography, failed to trigger de novo bone formation. The relative strength of the parameters affecting CaP-driven bone induction was as follows: surface feature size > surface feature morphology > substrate chemistry. BCP materials with needle-shaped sub-micron surface topography gave rise to accelerated bone formation and slower rate of resorption than a comparable TCP. These characteristics may be translated to improve bone healing in orthotopic defects.