Fibroblast/fibrocyte: surface interaction dictates tissue reactions to micropillar implants

Micropillar technology has shown great promise for medical implants or sensors in recent years. To study the influence of surface topography on cellular responses, polydimethylsiloxane (PDMS) micropillar arrays with pillar spacing (20-70 μm) and height (14-25 μm) have been fabricated. The influence of micropillar arrays on cellular behavior was tested both in vitro and in vivo. Interestingly, in vitro, we observe a distinct response for 3T3 fibroblasts and RAW 264.7 macrophages to the topographical cues tested. Attachment and proliferation of fibroblasts was substantially enhanced by increasing pillar height, whereas macrophage adherence is significantly diminished by reduced pillar spacing. When implanted in the subcutaneous cavity of BALB/c mice for 14 days, we find a prevailing trend with capsule cell density and capsule thickness increasing, as both pillar height and spacing rise. Collagen deposition and neoangiogenesis, two pivotal factors in granulation tissue maturation, are also observed to have a stronger response to the increase in both pillar height and spacing. In contradiction to our original hypothesis, we observed that fibroblasts rather than macrophages are a key contributor to the in vivo outcome of micropillar arrays. Investigation into fibroblast activation, however, revealed that recruited fibrocytes, rather than resident fibroblasts, correspond to the in vivo outcome. The results from this work support the critical and often overlooked role of fibrocytes in tissue response to biomaterial implants with varying topography.