The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth during bone healing (1). By infusing barium sulfate (BaSO4) into WT and Bgn-deficient mice we discovered the positive effect of Bgn in modulating angiogenesis during fracture healing. Using micro-computed tomography angiography we found significant differences in the vessel size and volume among other parameters. To further understand the mechanistic basis for this, we explored the relationship between Bgn and the anti-angiogenic protein endostatin. Immunohistochemistry (IHC) showed co-localization of Bgn and endostatin in regions of bone formation, with increased endostatin staining in Bgn-KO compared to WT at 14 days post-fracture. To further elucidate the relationship between Bgn and endostatin, an endothelial cell tube formation assay was used. This study showed that endothelial cells treated with endostatin had significantly decreased vessel length and vessel branches compared to untreated cells, while cells treated with endostatin and Bgn at a 1:1 molar ratio had vessel length and vessel branches comparable to untreated cells. This indicated that Bgn was able to mitigate the inhibitory effect of endostatin on endothelial cell growth. In summary, these results suggest that Bgn is needed for proper blood vessel formation during fracture healing, and one mechanism by which Bgn impacts angiogenesis is through inhibition of endostatin.

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Background The reverse sural artery flap (RSAF) is a popular option for patients with distal lower extremity defects who are not ideal candidates for free flap reconstruction. This is the first systematic review and pooled analysis of surgical characteristics, risk factors, and outcomes of the RSAF. Methods A systematic literature review was conducted. All studies reporting on patients undergoing RSAF reconstruction and their outcomes were included. Outcomes were pooled and analyzed using Fisher exact or χ2 test. Results Forty-three studies (479 patients, 481 flaps) were analyzed. The majority of patients were male (70.3%), and average ± SD age was 46.9 ± 16.7 years. Rates of smoking, diabetes mellitus (DM), and peripheral vascular disease (PVD) were 34.6%, 35.4%, and 12.3%, respectively. Defect etiologies were largely traumatic (60.4%). The most common defect location was the heel (40.8%). Flap modifications were reported in 123 flaps (25.6%). The most common modification was adipofascial extension (20.3%). Overall, the partial and total flap loss rates were 15.4% and 3.1%, respectively. Partial flap loss was significantly increased in smokers (28.9% vs 12.2% in nonsmokers, P = 0.0195). Technical modifications decreased the odds of partial necrosis by almost 3-fold compared with traditional RSAF reconstruction (7.2% vs 17.9%; odds ratio, 2.8 [1.4–5.8]; P = 0.0035). Patient age, DM, and PVD were not significantly associated with flap loss. Conclusions The RSAF remains a safe salvage option for patients with DM or PVD but should be used with caution in smokers. Technical modifications to minimize pedicle compression significantly reduce rates of partial necrosis.

The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2,959, 2,867, and 2,755 non-redundant proteins with peptide and protein false positive rates of <0.1% and <1%, respectively. Forty-three unambiguous protein isoforms were identified in iris, ciliary body, and RPE/choroid. Four “missing proteins” were identified in ciliary body based on ≥2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194.