A 3D in vitro model for assessing the influence of intraocular lens: Posterior lens capsule interactions on lens epithelial cell responses.

Posterior Capsule Opacification (PCO), the most frequent complication of cataract surgery, is caused by the infiltration and proliferation of lens epithelial cells (LECs) at the interface between the intraocular lens (IOL) and posterior lens capsule (PLC). According to the "no space, no cells, no PCO" theory, high affinity (or adhesion force) between the IOL and PLC would decrease the IOL: PLC interface space, hinder LEC migration, and thus reduce PCO formation. To test this hypothesis, an in vitro hemisphere-shaped simulated PLC (sPLC) was made to mimic the human IOL: PLC physical interactions and to assess their influence on LEC responses. Three commercially available IOLs with different affinities/adhesion forces toward the sPLC, including Acrylic foldable IOL, Silicone IOL, and PMMA IOL, were used in this investigation. Using the system, the physical interactions between IOLs and sPLC were quantified by measuring the adhesion force and interface space using an adhesion force apparatus and Optical Coherence Tomography, respectively. Our data shows that high adhesion force and tight binding between IOL and sPLC contribute to a small interface space (or "no space"). By introducing LECs into the in vitro system, we found that, with small interface space, among all IOLs, acrylic foldable IOLs permitted the least extent of LEC infiltration, proliferation, and differentiation (or "no cells"). Further statistical analyses using clinical data revealed that weak LEC responses are associated with low clinical PCO incidence rates (or "no PCO"). The findings support that the in vitro system could simulate IOL: PLC interplays and predict IOLs' PCO potential in support of the "no space, no cells, no PCO" hypothesis.

Histological Analysis of Regenerative Properties in Human Glenoid Labral Regions.

BACKGROUND: The healing capacity of the human glenoid labrum varies by tear location. Current evidence suggests that the healing capacity of meniscal and cartilage injuries relates to cellular composition and vascularity. However, little is known about the histological characteristics of the glenoid labrum and how they may affect healing potential in specific anatomic regions. HYPOTHESIS: Regenerative characteristics of the glenoid labrum differ based on the anatomic region. STUDY DESIGN: Descriptive laboratory study. METHODS: Human glenoid labra from fresh unpreserved cadavers were transversely sectioned in different anatomic regions. Masson trichrome stain was used to determine dense and loose extracellular matrix regions and vessel densities. Hematoxylin and eosin, Ki-67+, and CD90+/CD105+ stains were performed to determine total, proliferative, and progenitor cell densities, respectively. Regression models demonstrated relationships between vascular area, progenitor cell quantity, and probability of successful operation. RESULTS: Among all labral aspects, the superior glenoid labrum had the highest percentage (56.8% ± 6.9%) of dense extracellular matrix or avascular tissue (P < .1). The vascular region of the superior labrum had the fewest total cells (321 ± 135 cells/mm2; P < .01) and progenitor cells (20 ± 4 cells/mm2; P < .001). Vascular area was directly correlated with progenitor cell quantity (P = .006002). An increase in probability of successful operation was associated with a linear increase in vascular area (R2 = 0.765) and an exponential increase in progenitor cell quantity (R2 = 0.795). Subsequently, quadratic models of vascularity and progenitor cell quantity around the labral clock were used to assess relative healing potential. Quadratic models for percentage vascular area (P = 6.35e-07) and weighted progenitor cell density (P = 3.03e-05) around the labral clock showed that percentage vascular area and progenitor cell quantity increased as labral tissue neared the inferior aspect and diminished near the superior aspect. CONCLUSION: Anatomic regions of the glenoid labrum differ in extracellular matrix composition, vascularity, and cell composition. The superior glenoid labrum is deficient in vascularity and progenitor cells, which may explain the high failure rates for repairs in this location. CLINICAL RELEVANCE: Improved understanding of the composition of distinct glenoid labral positions may help to improve therapeutic strategies for labral pathology.

Biomolecule-releasing bioadhesive for glenoid labrum repair through induced host progenitor cell responses.

Glenoid labral tears occur with repetitive dislocation events and are common injuries observed in shoulder arthroscopic procedures. Although surgery can restore shoulder anatomy, repair is associated with poor clinical outcomes, which may be attributed to the poor regenerative capability of glenoid labral fibrocartilage. Thus, this study was designed to assess whether in situ tissue regeneration via biomolecule-stimulated recruitment of progenitor cells is a viable approach for the regeneration of labral tears. We developed a click chemistry-based bioadhesive to improve labral repair and reduce local inflammatory responses due to trauma. Additionally, we previously identified the presence of progenitor cells in the human labrum, which can be recruited by platelet-derived growth factor (PDGF). Thus, we hypothesized that PDGF-releasing adhesives could induce the regenerative responses of progenitor cells at the injury site to improve labral healing. In a rat glenoid labral tear model, we evaluated the effect of PDGF-releasing adhesives on promoting progenitor cells to participate in labral tear healing. After 3 and 6 weeks, the labrum was histologically analyzed for inflammatory responses, progenitor cell recruitment, proliferation, and extracellular matrix (ECM) production (collagen and glycosaminoglycan). Our results showed that adhesives alone considerably reduced local inflammatory responses and labral tissue dissolution. PDGF-releasing adhesives significantly increased progenitor cell recruitment, proliferation, and ECM production. These results demonstrate that by accelerating autologous progenitor cell responses, PDGF-releasing adhesives represent a novel clinically relevant strategy to improve the healing of glenoid labral tears.