Nanofat is increasingly applied in plastic surgery for the improvement of scar quality and skin rejuvenation. However, little is known about the underlying regenerative mechanisms. Therefore, we herein investigated nanofat grafts in a murine dorsal skinfold chamber model. Nanofat generated from subcutaneous, inguinal adipose tissue of green fluorescent protein (GFP)⁺ C57BL/6 male and female donor mice was injected intracutaneously into dorsal skinfold chambers of gender-matched GFP⁻ wild-type mice. The vascularization and tissue composition of the grafted nanofat were analyzed by means of intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. The freshly generated nanofat consisted of small fragments of perilipin⁺ adipocytes surrounded by Sirius red⁺ collagen fibers and still contained intact CD31⁺/GFP⁺ vessel segments. After transplantation into the dorsal skinfold chamber, these vessel segments survived and developed interconnections to the surrounding CD31⁺/GFP⁻ host microvasculature. Accordingly, the grafted nanofat rapidly vascularized and formed new microvascular networks with a high functional microvessel density on day 14 without marked differences between male and female mice. Even though further research is needed to confirm these findings, the present study suggests that nanofat boosts tissue vascularization. Thus, nanofat may represent a versatile resource for many applications in tissue engineering and regenerative medicine.

Background: Flap procedures are widely used in clinical reconstructive surgery. Since ische­mia-associated complications, e.g., wound breakdown or tissue necrosis, are still a great challenge in flap surgery, experimental flap models are widely used to study flap physiology and to evaluate treatment strategies to prevent these complications. Summary: Since rodents in general, and mice and rats in particular, are widely used in experimental flap models, we give an overview of the most common flap models in rodents, including the cremaster flap, the osteomyocutaneous flap, the McFarlane flap, the ear flap, and the dorsal skinfold chamber. Key Messages: Rodent flap models in experimental surgery are manifold and have a long history. These models play an important role in training surgical techniques, understanding flap physiology, defining flap anatomy and vascularity, and developing treatment regimens to prevent the necrosis of ischemically challenged tissue. However, it is important to be aware of the advantages and disadvantages of the single flap models concerning the possible time span of the experiment, the degree of difficulty, and the reproducibility and the translation of the results in humans.

The treatment of wounds using the body’s own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)⁺ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP⁺ vascular and lymph vessel fragments, which interconnected with the GFP⁻ vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.

Achieving precision in microsurgery requires skill, adequate instruments and magnification, as well as extensive training. Dedicated surgical robotic systems have enhanced and expanded the application of (super-)microsurgical techniques by introducing motion scaling and providing improved surgeon ergonomics. In this prospective preclinical trial, we analyzed the learning curve in robotic assisted microsurgery in 13 participants including medical students, residents, and attending physicians. Data on demographics as well as prior experience in surgery, microsurgery, and gaming were collected. In three study sessions, the participants performed nine microsurgical anastomoses each on 2 mm vessel models using the Symani^® Surgical System in combination the VITOM 3D exoscope. A senior expert microsurgeon reviewed the de-identified and blinded videos and scored all anastomoses using a modified “Structured Assessment of Microsurgical Skills” (SARMS) score. All participants significantly reduced their time needed per anastomosis and their overall SARMS score, as well as individual scores for motion and speed throughout the trial. We saw a significant correlation of prior years of practice in surgery with the overall mean time and mean SARMS score. In a separate analysis of the three sessions, this influence could no longer be seen in the last session. Furthermore, we found no significant effect of gender, age, hand dominance, or gaming experience on speed and quality of the anastomoses. In this study of 117 robotic assisted anastomoses, a rapid improvement of performance of all participants with different surgical skills levels could be shown, serving as encouraging evidence for further research in the implementation of microsurgical robotic systems.

Adipose tissue resorption after fat grafting is a major drawback in plastic and reconstructive surgery, which is primarily caused by the insufficient blood perfusion of the grafts in the initial phase after transplantation. To overcome this problem, several promising strategies to boost the vascularization and, thus, increase survival rates of fat grafts have been developed in preclinical studies in recent years. These include the angiogenic stimulation of the grafts by growth factors and botulinum neurotoxin A, biologically active gels and cellular enrichment as well as the physical and pharmacological stimulation of the transplantation site. To transfer these approaches into future clinical practice, it will be necessary to establish standardized procedures for their safe application in humans. If this succeeds, the surgical outcomes of fat grafting may be markedly improved, resulting in a significant reduction of the physical and psychological stress for the patients.

Bromelain has previously been shown to prevent ischemia-induced necrosis in different types of tissues. In the present study, we, therefore, evaluated for the first time, the tissue-protective effects of bromelain in musculocutaneous flaps in mice. Adult C57BL/6N mice were randomly assigned to a bromelain treatment group and a control group. The animals were treated daily with intraperitoneal injections of 20 mg/kg bromelain or saline (control), starting 1 h before the flap elevation throughout a 10-day observation period. The random-pattern musculocutaneous flaps were raised on the backs of the animals and mounted into a dorsal skinfold chamber. Angiogenesis, nutritive blood perfusion and flap necrosis were quantitatively analyzed by means of repeated intravital fluorescence microscopy over 10 days after surgery. After the last microscopy, the flaps were harvested for additional histological and immunohistochemical analyses. Bromelain reduced necrosis of the critically perfused flap tissue by ~25%. The bromelain-treated flaps also exhibited a significantly higher functional microvessel density and an elevated formation of newly developed microvessels in the transition zone between the vital and necrotic tissues when compared to the controls. Immunohistochemical analyses demonstrated a markedly lower invasion of the myeloperoxidase-positive neutrophilic granulocytes and a significantly reduced number of cleaved caspase 3-positive apoptotic cells in the transition zone of bromelain-treated musculocutaneous flaps. These findings indicate that bromelain prevents flap necrosis by maintaining nutritive tissue perfusion and by suppressing ischemia-induced inflammation and apoptosis. Hence, bromelain may represent a promising compound to prevent ischemia-induced flap necrosis in clinical practice.