Comparable Effects on Healing between Autologous Diabetic Adipose-Derived Stem Cells and Allogeneic Normal Counterparts.

BACKGROUND: Adipose-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. Although the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds. METHODS: Diabetic ASCs (DMA) and nondiabetic ASCs were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10- to 12-week-old db/db mice. Wound size was measured semiweekly until day 28, and histologic and molecular analyses were performed at day 14. RESULTS: Both ASCs had fibroblast-like morphology and were CD44 + /CD90 + /CD34 - /CD45 - at passage 4. Compared with nondiabetic ASCs in vitro, DMA proliferative capability was restored by passage 4 ( P > 0.05). Although DMA osteogenesis was attenuated ( P < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 ( P > 0.05). In vivo experiments showed that, compared with phosphate-buffered saline control, both ASCs are comparable in improving wound healing ( P < 0.0001), angiogenesis ( P < 0.05), epithelial cell proliferation ( P < 0.05), and granulation tissue formation ( P < 0.0001). CONCLUSIONS: In both in vitro and in vivo murine models, DMAs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, reepithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments. CLINICAL RELEVANCE STATEMENT: This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients' own ASCs to treat their wounds, bypassing any concerns of cross-host sourcing issues in regenerative medicine.

What COVID Restrictions Have Taught Us About Visiting Subinternships.

BACKGROUND: Integrated plastic surgery applicants complete among the highest number of visiting audition rotations of any specialty. In the 2021 match, we observed that the elimination of audition rotations and in-person interviews drastically increased the number of applicants who matched at their home program. We sought to evaluate the effect of applicants participating in one selective visiting subinternship rotation on home program match rates. METHODS: Top 50 plastic surgery residency programs were identified by 2021 Doximity rankings. Publicly available, online plastic surgery match spreadsheets were used to collect available information including matched applicants' medical school, the institution at which they matched, whether they matched at their home institution, and whether they had previous communication with their matched program including research year or visiting subinternship completed. RESULTS: Fourteen percent of applicants matched at their home institution in 2022, comparable with recent prepandemic rates of 14.1% and 16.7%, versus 24.1% in 2021. The largest effect was observed among the top 25 programs. Separately, approximately 70% of applicants provided self-reported information on whether they completed a subinternship. Among the top 50 programs, 39.0% of applicants completed an audition rotation at the institution at which they eventually matched. CONCLUSIONS: The allowance of medical students to perform only one visiting subinternship in the 2022 match cycle normalized home match rates to the prepandemic baseline, possibly driven by a large proportion of students matching at their visiting rotation institution. Perhaps from both a program and applicant standpoint, 1 away rotation may provide sufficient exposure for eventual match success.

Comparison of Yield, Purity, and Functional Properties of Large-Volume Exosome Isolation Using Ultrafiltration and Polymer-Based Precipitation.

BACKGROUND: Mesenchymal stem cell-derived exosomes are known to produce effects similar to those of source cells and therefore represent a new approach in cell-free regenerative medicine. Their potential clinical application demands efficient isolation of stable and functional exosomes from a large volume of biological fluid. METHODS: Exosomes from adipose-tissue conditioned medium of the same volume were isolated using either (1) ultrafiltration with size exclusion or (2) ExoQuick-TC. The isolated exosomes were characterized by protein concentration, particle size, exosomal marker expression, RNA expression profiles, and roles in dermal fibroblast proliferation and migration. RESULTS: Both isolation methods produced exosomes within the size range defined for exosomes (50 to 200 nm) and common markers were enriched. Compared to the ExoQuick-TC precipitation method, the ultrafiltration method produced a significantly higher protein yield (p < 0.001) but a lower particle-to-protein ratio (p < 0.05); it also yielded higher RNA contents from the same fat tissue indicated by housekeeping genes, but with overall lower purity. The expression of several mRNAs and miRNAs related to tissue regeneration showed that there was no statistical difference between both methods, except miR-155 and miR-223 (p < 0.05). However, there was no difference in overall fibroblast proliferation and migration between exosomes isolated by these two methods. CONCLUSIONS: Ultrafiltration with size exclusion demonstrated higher yields, acceptable purity, and comparable biophysical properties and biological functions to the more expensive commercial precipitation method. Therefore, it may conceivably be translated into yield-efficient and cost-effective modalities for therapeutic purposes. CLINICAL RELEVANCE STATEMENT: Ultrafiltration with size exclusion may be amenable for exosome isolation from large-volume complex fluids such as tissue conditioned media for clinical application in future regenerative medicine.

Opioid-sparing Strategies in Alloplastic Breast Reconstruction: A Systematic Review.

INTRODUCTION: Pain and discomfort are frequently experienced following mastectomy with concomitant breast implant- or tissue expander-based alloplastic breast reconstruction (AlBR). Unfortunately, postoperative opioids have decreased efficacy in AlBR, short-term complication profiles, and are fraught by long-term dependence. This systematic review aims to identify opioid-sparing pain management strategies in AlBR. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane Central Register was performed in September 2018. PRISMA guidelines were followed, and the review was prospectively registered in PROSPERO (CRD42018107911). The search identified 1184 articles. Inclusion criteria were defined as patients 18 years or older undergoing AlBR. RESULTS: Fourteen articles were identified assessing opioid-sparing strategies in AlBR. This literature included articles evaluating enhanced recovery protocols (two), intercostal blocks (two), paravertebral blocks (four), liposomal bupivacaine (three), diclofenac (one), and local anesthesia infusion pumps (two). The literature included five randomized trials and nine cohort studies. Study characteristics, bias (low to high risk), and reporting outcomes were extensively heterogeneous between articles. Qualitative analysis suggests reduced opioid utilization in enhanced recovery after surgery (ERAS) pathways, paravertebral blocks, and use of liposomal bupivacaine. CONCLUSIONS: A variety of opioid-sparing strategies are described for pain management in AlBR. Multimodal analgesia should be provided via ERAS pathways as they appear to reduce pain and spare opioid use. Targeted paravertebral blocks and liposomal bupivacaine field blocks appear to be beneficial in sparing opioids and should be considered as essential components of ERAS protocols. Additional prospective, randomized trials are necessary to delineate the efficacy of other studied modalities.

Lateralization and Decreased Neck-Shaft Angle Reduces Scapular Notching and Heterotopic Ossification.

BACKGROUND: Lateralization of the glenosphere in reverse shoulder arthroplasty likely mitigates scapular notching; however, there is a paucity of data evaluating the effect of heterotopic ossification (HO) at the inferior aspect of the glenoid neck. METHODS: We retrospectively reviewed 107 consecutive reverse shoulder arthroplasty patients between April 2013 and April 2016. During the study period, the surgeon switched from a 2.5-mm lateral center of rotation and a 155° neck-shaft angle (NSA) to a 6- or 10-mm lateralized design with a 135° NSA. Preoperative and minimum 2-year postoperative patient-reported outcomes and range of motion were collected. Two-year postoperative radiographs were evaluated for scapular notching and HO. RESULTS: The lateralized center of rotation implant was 72% less likely to develop HO and 85% less likely to produce scapular notching than the medialized prosthesis. CONCLUSION: Implants with laterally offset glenospheres and 135° NSA may decrease postoperative HO and scapular notching. LEVEL OF EVIDENCE: Level III, retrospective cohort study.