The ability to use the body’s resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research. Here, we tested the effect of topical application of blood-derived hypoxia preconditioned serum (HPS) on wound healing in a murine wound model. Alginate hydrogels loaded with two different HPS concentrations (10 and 40%) were applied topically on full-thickness wounds created on the back of immunocompromised mice. We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Healed tissue samples were investigated on post-operative day 15 (POD 15) by immunohistology and showed an increase in lymphatic vessels (LYVE-1) up to 45% with HPS-40% application, while at this stage, vascularization (CD31) was comparable in the HPS-treated and NT groups. Furthermore, the expression of proliferation marker Ki67 was greater on POD 15 in the NT-group compared to HPS-treated groups, in accordance with the earlier completion of wound healing observed in the latter. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice.

Strategies for therapeutic lymphangiogenesis are gradually directed toward the use of growth factor preparations. In particular, blood-derived growth factor products, including Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP), are both clinically employed for accelerating tissue repair and have received considerable attention in the field of regenerative medicine research. In this study, a comparative analysis of HPS and PRP was conducted to explore their lymphangiogenic potential. We found higher pro-lymphangiogenic growth factor concentrations of VEGF-C, PDGF-BB, and bFGF in HPS in comparison to normal serum (NS) and PRP. The proliferation and migration of lymphatic endothelial cells (LECs) were promoted considerably with both HPS and PRP, but the strongest effect was achieved with HPS-40% dilution. Tube formation of LECs showed the highest number of tubes, branching points, greater tube length, and cell-covered area with HPS-10%. Finally, the effects were double-validated using an ex vivo lymphatic ring assay, in which the highest number of sprouts and the greatest sprout length were achieved with HPS-10%. Our findings demonstrate the superior lymphangiogenic potential of a new generation blood-derived secretome obtained by hypoxic preconditioning of peripheral blood cells—a method that offers a novel alternative to PRP.

Harnessing the body’s intrinsic resources for wound healing is becoming a rapidly advancing field in regenerative medicine research. This study investigates the effects of the topical application of a novel porcine Hypoxia Preconditioned Serum Hydrogel (HPS-H) on wound healing using a minipig model over a 21-day period. Porcine HPS exhibited up to 2.8× elevated levels of key angiogenic growth factors (VEGF-A, PDGF-BB, and bFGF) and demonstrated a superior angiogenic effect in a tube formation assay with human umbilical endothelial cells (HUVECs) in comparison to porcine normal serum (NS). Incorporating HPS into a hydrogel carrier matrix (HPS-H) facilitated the sustained release of growth factors for up to 5 days. In the in vivo experiment, wounds treated with HPS-H were compared to those treated with normal serum hydrogel (NS-H), hydrogel only (H), and no treatment (NT). At day 10 post-wounding, the HPS-H group was observed to promote up to 1.7× faster wound closure as a result of accelerated epithelialization and wound contraction. Hyperspectral imaging revealed up to 12.9% higher superficial tissue oxygenation and deep perfusion in HPS-H-treated wounds at day 10. The immunohistochemical staining of wound biopsies detected increased formation of blood vessels (CD31), lymphatic vessels (LYVE-1), and myofibroblasts (alpha-SMA) in the HPS-H group. These findings suggest that the topical application of HPS-H can significantly accelerate dermal wound healing in an autologous porcine model.

The fingers' tactile sensibility is essential in surgery, especially in microsurgery. Therefore, surgeons seeking to improve their performance often prefer certain glove brands and wearing habits. There is the need of objectively testing these glove wearing conditions and determine the effect of surgical experience with regard to tactile sensibility by comparing surgeons with non-surgeons. This cross-sectional single-center pilot-study was conducted between June and August 2021. Two groups of 27 surgeons and 27 non-surgeons underwent two-point-discrimination (2PD) and Semmes-Weinstein monofilament testing (SWMT) of both index fingers with bare hands and with wearing six different brands of surgical gloves. Different wearing conditions, such as single-gloving, double-gloving, well-fitted, under- and oversized gloves, were evaluated within and between the groups. Most glove types decreased tactile sensibility (2PD and SWMT) of surgeons and non-surgeons. Interestingly, the thinnest gloves showed similar 2PD values to bare hands in both groups. Double-gloving negatively impacted SWMT, without influencing 2PD. Undersized gloves showed better 2PD and SWMT than well-fitted gloves, while oversized gloves showed no tactile drawbacks. With bare hands and certain glove conditions, the surgeons' 2PD and SWMT was significantly better than the non-surgeons', indicating a positive effect of surgical experience on tactile sensibility. Our study demonstrated the positive impact of surgical experience on tactile sensibility, as demonstrated by the surgeons. The sensibility of the gloved hand varies on the surgical glove type, but favors thinner gloves, single gloving (rather than double gloving) and undersized or well-fitted gloves.

Interest in discovering new methods of employing natural growth factor preparations to promote bone fracture healing is becoming increasingly popular in the field of regenerative medicine. In this study, we were able to demonstrate the osteogenic potential of hypoxia preconditioned serum (HPS) on human osteoblasts in vitro. Human osteoblasts were stimulated with two HPS concentrations (10% and 40%) and subsequently analyzed at time points of days 2 and 4. In comparison to controls, a time- and dose-dependent (up to 14.2× higher) proliferation of osteoblasts was observed after 4 days of HPS-40% stimulation with lower lactate dehydrogenase (LDH)-levels detected than controls, indicating the absence of cytotoxic/stress effects of HPS on human osteoblasts. With regards to cell migration, it was found to be significantly faster with HPS-10% application after 72 h in comparison to controls. Further osteogenic response to HPS treatment was evaluated by employing culture supernatant analysis, which exhibited significant upregulation of OPG (Osteoprotegerin) with higher dosage (HPS-10% vs. HPS-40%) and longer duration (2 d vs. 4 d) of HPS stimulation. There was no detection of anti-osteogenic sRANKL (soluble Receptor Activator of NF-κB Ligand) after 4 days of HPS stimulation. In addition, ALP (alkaline phosphatase)-enzyme activity, was found to be upregulated, dose-dependently, after 4 days of HPS-40% application. When assessing ossification through Alizarin-Red staining, HPS dose-dependently achieved greater (up to 2.8× higher) extracellular deposition of calcium-phosphate with HPS-40% in comparison to controls. These findings indicate that HPS holds the potential to accelerate bone regeneration by osteogenic promotion of human osteoblasts.

Aesthetic surgery training renders to be challenging to acquire sufficient hands-on experience during residency. To resolve this problem, the “Munich Model” was established in our clinic: Senior residents perform aesthetic surgeries, supervised by an experienced plastic surgeon while patients benefit from reduced surgery costs. With this model, we hypothesize no significant differences in the postoperative outcome between procedures performed by residents and plastic surgeons. Between August 2012 and December 2017, 481 aesthetic surgeries were included in this retrospective single-center study, of which 283 were performed by residents and 198 by plastic surgeons. Procedures included mastopexy, abdominoplasty, extremity lift, breast reduction, breast augmentation, facial surgery, aesthetic liposuction and lipedema liposuction. Postoperative outcomes were compared regarding surgery time, time of drain removal, inpatient length of stay, duration of wound healing, perioperative blood loss and occurrence of major (surgical revision needed) and minor complications (no surgery needed). We found no significant differences in aesthetic surgical procedures between residents and board-certified plastic surgeons in the outcome measures of surgery duration, time of drain removal, inpatient length of stay, perioperative blood loss and complication rate, including major and minor complications. Only the inpatient stay was prolonged in aesthetic liposuctions performed by residents. This study demonstrates comparatively that supervised aesthetic surgeries at a university hospital utilizing the “Munich Model” widely meet the specialist surgeons’ standards.