Design of 3D scaffolds that can facilitate proper survival, proliferation, and differentiation of progenitor cells is a challenge for clinical applications involving large connective tissue defects. Cell migration within such scaffolds is a critical process governing tissue integration. Here, we examine effects of scaffold pore diameter, in concert with matrix stiffness and adhesivity, as independently tunable parameters that govern marrow-derived stem cell motility. We adopted an “inverse opal” processing technique to create synthetic scaffolds by crosslinking poly(ethylene glycol) at different densities (controlling matrix elastic moduli or stiffness) and small doses of a heterobifunctional monomer (controlling matrix adhesivity) around templating beads of different radii. As pore diameter was varied from 7 to 17 µm (i.e., from significantly smaller than the spherical cell diameter to approximately cell diameter), it displayed a profound effect on migration of these stem cells—including the degree to which motility was sensitive to changes in matrix stiffness and adhesivity. Surprisingly, the highest probability for substantive cell movement through pores was observed for an intermediate pore diameter, rather than the largest pore diameter, which exceeded cell diameter. The relationships between migration speed, displacement, and total path length were found to depend strongly on pore diameter. We attribute this dependence to convolution of pore diameter and void chamber diameter, yielding different geometric environments experienced by the cells within.

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PurposeTo evaluate alterations on optical coherence tomography angiography (OCT-A) and quantitatively assess alterations in the ellipsoid zone (EZ) in eyes with macular telangiectasia type 2 (MacTel type 2).MethodsThe Observational Assessment of Visualizing and Analyzing Vessels With Optical Coherence Tomography Angiography in Retinal Diseases study is an institutional review board-approved prospective, observational study investigating OCT-A in macular disease. Patients underwent spectral-domain (SD)-OCT and OCT-A imaging at a single visit. SD-OCT data were analyzed using a novel OCT EZ-mapping software to obtain linear, area, and volumetric measurements of the EZ-retinal pigment epithelium (RPE) complex across the macular cube. OCT-A retinal capillary density was measured using the Optovue Avanti split-spectrum amplitude-decorrelation angiography algorithm. EZ-RPE parameters were compared to age-matched, sex-matched controls.ResultsFourteen eyes of seven patients (mean age, 59 ± 6.5 years) were analyzed. Mean visual acuity was 20/45 (range, 20/20–20/150). EZ-RPE central foveal mean thickness was 27.8 ± 6.7 μm, EZ-RPE central foveal thickness was 22.1 ± 21.6 μm, EZ-RPE central foveal area was 0.17 ± 0.04 mm2, and EZ-RPE central subfield volume was 0.017 ± 0.012 mm3. Each of these measurements was significantly inversely correlated with visual acuity (P < 0.02). In addition, all of these measurements were significantly reduced compared to controls (all P ≤ 0.005). OCT-A showed a reduced parafoveal vessel density of 50.8% temporally compared to 53.8% nasally (P = 0.01) in the superficial vascular plexus. In the deep vascular plexus, similar findings were noted with a parafoveal vessel density of 56.7% temporally and 58.8% nasally (P = 0.01).ConclusionsAbnormalities in EZ-RPE thickness, area, and volume are correlated with visual acuity in MacTel type 2, and may provide quantitative markers to measure disease progression and treatment response. OCT-A was a useful adjunct for determining disease severity.