Monocytes contribute to a pro-healing response in 40 mu m diameter uniform-pore, precision-templated scaffolds

Porous precision-templated scaffolds (PTS) with uniformly distributed 40 mu m spherical pores have shown a remarkable ability in immunomodulating resident cells for tissue regeneration. While the pore size mediated pro-healing response observed only in 40 mu m pore PTS has been attributed to selective macrophage polarization, monocyte recruitment and phenotype have largely been uncharacterized in regulating implant outcome. Here, we employ a double transgenic mouse model for myeloid characterization and a multifaceted phenotyping approach to quantify monocyte dynamics within subcutaneously implanted PTS. Within 40 mu m PTS, myeloid cells were found to preferentially infiltrate into the scaffold. Additionally, macrophage receptor with collagenous structure (MARCO), an innate activation marker, was significantly upregulated within 40 mu m PTS. When 40 mu m PTS were implanted in monocyte-depleted mice, the transcription of MARCO was significantly decreased and an increase in pro-inflammatory inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF alpha) were observed. Typical of a foreign body response (FBR), 100 mu m PTS significantly upregulated pro-inflammatory iNOS, secreted higher amounts of TNF alpha, and displayed a pore size dependent morphology compared to 40 mu m PTS. Overall, these results identify a pore size dependent modulation of circulating monocytes and implicates MARCO expression as a defining subset of monocytes that appears to be responsible for regulating a pro-healing host response.