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Erythropoietin (EPO) is a glycoprotein hormone exerting pro-angiogenic and anti-inflammatory effects. The present study investigated whether this beneficial profile of action is suitable to improve the in vivo performance of nanofat, an emulsified fat derivative that is clinically used in plastic and reconstructive surgery.

Nanofat was mechanically prepared from subcutaneous adipose tissue of green fluorescent protein (GFP)⁺ C57BL/6J mice and incubated for 1 hour in Hank’s Balanced Salt Solution, with or without EPO (3 IU/mL). The pretreated nanofat was seeded onto dermal substitutes, which were implanted into dorsal skinfold chambers of GFP⁻ C57BL/6J mice. The implants were analyzed over 14 days by intravital fluorescence microscopy, histology, and immunohistochemistry. Data were reported as means ± SEM, with statistical significance set at p < 0.05.

EPO-pretreated nanofat significantly accelerates and enhances functional microvessel density at the border zones and center of the implants, compared to controls. This was associated with a reduced inflammatory response to the dermal substitutes, as indicated by fewer adherent leukocytes in venules of the host tissue. Histological and immunohistochemical analyses further revealed an improved implant integration with increased collagen I deposition and a higher density of nanofat-derived CD31⁺/GFP⁺ microvessels, along with a reduced macrophage and neutrophil infiltration.

These findings identify short-term pretreatment with EPO as an effective strategy to boost the vascularization and regenerative capacity of nanofat, potentially easily translatable into the daily clinic.

Hypoxic preconditioning is increasingly being explored as a strategy to enhance the survival and vascularization of fat grafts. However, its impact on the vascularization properties of nanofat has not been investigated so far.

Nanofat was generated from the inguinal fat of green fluorescent protein (GFP)-positive C57BL/6J donor mice and exposed to hypoxia (1% O2) for 24 h. Subsequently, the effects of this stress on cell viability, gene expression and angiogenesis-related factors was assessed ex vivo by means of flow cytometry, immunohistochemistry, qRT-PCR and proteome profiler arrays. Non-preconditioned nanofat served as control. For in vivo analyses, dermal substitutes were either seeded with preconditioned or non-preconditioned nanofat and transferred into dorsal skinfold chambers of wild-type C57BL/6J recipient mice. Vascularization and tissue integration were evaluated by means of repeated intravital fluorescence microscopy, histology and immunohistochemistry. All values were expressed as means±SEM. Statistical significance was accepted for p <= 0.05.

Ex vivo analyses revealed that hypoxic preconditioning does neither affect apoptotic nor necrotic cell death within nanofat but significantly upregulates the expression of hypoxia-inducible factor (HIF)-1α and stromal cell-derived factor (SDF)-1 compared to non-preconditioned nanofat. Moreover, preconditioned nanofat exhibited a pro-angiogenic protein expression profile. Unexpectedly, however, implants seeded with preconditioned nanofat exhibited a significantly reduced functional microvessel density when compared to non-preconditioned controls. Immunohistochemical analyses also confirmed a lower microvessel density within the implants of the preconditioned group.

These findings suggest that hypoxic preconditioning at 1% O2 for 24 h cannot be recommended for enhancing the regenerative in vivo vascularization capacity of nanofat. Therefore, milder preconditioning protocols with shorter periods of hypoxia or higher oxygen levels should be alternatively tested in future studies.

To present a case series of ten procedures in seven patients where flap coverage was indicated but was declined, unfeasible, or unaffordable and where a topically applied regenerative matrix of autologous fat with Platelet rich fibrin matrix (PRFM) resulted in spontaneous early vascularization of the entire matrix, thus obviating the need for a flap. Following the success of the index case, the technique was used successfully in ten situations, achieving coverage over exposed bone, tendon, hardware, neurovascular bundles, and small joints.

The technique was an accidental discovery. The index case was a 4th degree iatrogenic burn of the skin, soft tissues and tibia following Radiofrequency ablation of bony tumor in a boy. After multiple debridements and antibiotic, a flap was indicated to cover 8x5 cm wound with 4x2 cm exposed bone, but consent was refused by parents. We decided to use regenerative techniques to improve the wound. Fat was harvested by liposuction (2.5-mm cannula), PRFM was prepared by Choukroun technique. Fat and fragmented PRFM were injected peri-wound. Finally, PRFM gel and condensed fat (“matrix”) were used to fill the defect. A Collagen dressing was applied. NPWT was applied from next day for 4 days. On 6th day the entire block of filled fat was vascularized, this was a surprise. Serial photographic documentation was performed till healing. After this accidental discovery, the same technique was used in all cases where flap was declined or unfeasible or unaffordable. Core biopsies were obtained in two cases. Outcome measures included stability of coverage, complications, and practicality.

Complete vascularization occurred in all cases within 6–14 days. Five healed by secondary epithelialization and two required skin grafting. Healing was stable in all with follow ups of 16 to 96 months. Biopsies demonstrated capillary ingrowth, fibroblast proliferation, and collagen deposition without necrosis or acute inflammation. All patients were happy with the method and outcome and one patient preferred it for his second ulceration. It was easy, reproducible and without complications. It worked even in presence of moderate infection.

Composite autologous fat–PRFM matrix grafting assisted by NPWT is a novel technique and may reproduce key functions of flap coverage in selected complex wounds. Further bigger study is warranted.

Nanofat, an autologous fat derivative, has shown to enhance the vascularization and tissue integration of dermal substitutes, frequently used in the treatment of large full-thickness skin defects. However, implants seeded with untreated nanofat exhibit a rather late onset of vascularization. Exposure to high glucose levels can activate vascular endothelial cells and promote angiogenesis. Therefore, the aim of the present study was to investigate whether short-term incubation of nanofat in a high-glucose solution (30 mM) improves its vascularization capacity.

To obtain nanofat, white adipose tissue was harvested from green fluorescent protein (GFP)⁺ C57BL/6J donor mice, mechanically processed, and incubated for 1 h in Hank’s Balanced Salt Solution with or without (control) the addition of glucose (30 mM). Thereafter, the incubated nanofat was seeded onto dermal substitutes (diameter: 4 mm), which were implanted into the dorsal skinfold chambers of GFP⁻ recipient mice. The vascularization and tissue integration of the seeded implants were analyzed by means of intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. Data were expressed as means ± SEM, with statistical significance defined as p<0.05.

High-glucose-pretreated nanofat enhanced vascularization of implanted dermal substitutes without inducing a stronger immune response compared to controls. High-glucose-pretreated nanofat significantly increased the density of blood-perfused microvessels in the border zones (~3.6-fold increase) and CD31⁺/GFP⁺ microvessels (~3-fold increase) within the implants. Accordingly, high-glucose-pretreated nanofat also enhanced tissue integration of the implants, as demonstrated by the increased deposition of type I collagen (~2.9-fold increase).

These findings suggest that short-term exposure of nanofat to high levels of glucose enhances its regenerative properties when seeded onto dermal substitutes. Hence, this novel approach represents a promising and applicable translatable strategy into clinical use to improve outcomes in the treatment of full-thickness skin defects.

Peripheral nerve injuries present a great clinical challenge. Although the peripheral nervous system possesses an intrinsic capacity for regeneration, conventional surgical approaches may not achieve complete functional recovery. A promising avenue is cells transplantation. However, it’s success is often undermined by immune-mediated graft rejection. Emerging local immunomodulating strategies may offer the potential to fine-tune the immune microenvironment at the graft site, thereby obviating the deleterious effects associated with systemic immunosuppression, and facilitate effective cell grafting for full functional recovery.

In this scoping review, we examined strategies of local immune modulation and evasion in cell transplantation for peripheral nerve repair. As of March 2025, 6115 records were identified (901 in Medline, 4988 in Embase, 226 in Cochrane), with 283 studies retained after screening. By integrating evidence from immunology, biomaterials, and regenerative medicine, this review outlines current mechanistic approaches, their limitations, and their broader relevance across regenerative therapies.

Five methods appeared to be the most researched which are encapsulation technics, biomaterial functionalisation, cells modifications, co-transplantations and other nerve specific. Our findings also indicate that, although each strategy exhibits substantial promises, the multifaceted nature of both the immune response and the tissue regeneration may necessitate a multi-targeted approached to achieve a sustained graft protection.

A deeper understanding of the intercellular “crosstalk” underpinning graft rejections may be critical for advancing cell transplantation therapies that priorities local immunomodulation. Future development of synergistic intervention targeting multiple immune components may be necessary to realise true successful immunotolerance.

Inflammation resolution is fundamental for optimal wound healing. Specialized pro-resolving mediators (SPMs)—bioactive lipids derived from omega-3 fatty acids (EPA, DHA)—actively orchestrate the cessation of inflammation, promote tissue regeneration, and modulate scar formation without inducing immunosuppression. Unlike traditional anti-inflammatory therapies that suppress immune responses, SPMs represent a paradigm shift by actively resolving inflammation while maintaining host defense. This review examines the potential applications of SPMs in plastic surgery and the role of omega-3 supplementation in enhancing endogenous SPM production.

A systematic literature search was conducted, including preclinical and clinical studies investigating SPM mechanisms, its effects on wound healing, and the outcomes of omega-3 supplementation. No publication year restrictions were applied to ensure comprehensive coverage of fundamental and recent studies.

SPMs accelerate wound healing through multiple mechanisms: inhibition of neutrophil infiltration, enhanced macrophage phagocytosis of debris and apoptotic cells, and modulation of fibroblast activity, preventing excessive collagen deposition. Topical Lipoxin A4 administration in animal models significantly reduced inflammatory infiltrate and collagen fiber density, improving scar appearance on validated scales. Resolvin D2 limited secondary necrosis in burn wounds, while Resolvin D1 attenuated post-burn mechanical allodynia. SPMs demonstrated antimicrobial activity against common pathogens, including S. aureus and E. coli, reducing infection risk without compromising immune function. Omega-3 supplementation (EPA/DHA 1-4g/day) significantly increases circulating SPM levels, offering a practical preoperative strategy to enhance the body's endogenous resolution capacity.

SPMs represent a promising therapeutic avenue in plastic surgery, offering improved wound healing, reduced scarring, and protection against infection. Omega-3 supplementation provides an accessible strategy to enhance endogenous SPM production. Further clinical trials are warranted to establish standardized protocols and validate these findings in human surgical patients.

Surgical literature associates wound edge trauma with infection risk and problematic healing. Running subcuticular and cuticular sutures are among the most common in Plastic, Reconstructive, and Aesthetic Surgery. Demonstrated herein are running subcuticular and cuticular suturing techniques eliminating wound edge trauma via forceps compression. These techniques are documented videographically in in vitro synthetic (Syndaver^™) tissue models, with photographic outcomes in 40 human patients.

In vitro synthetic (Syndaver, saline/fiber/dye, novel to Europe) abdominal skin tissue plates were excised with 4 x 1cm ellipses via scalpel to the
subcutaneous layer. Metzenbaum scissors undermined 2cm peripherally, and dermal wound edges were opposed with monofilament poliglecaprone buried interrupted sutures. Running subcuticular or cuticular polypropylene sutures closed the upper dermal and epidermal surface defects. Modified forceps techniques restricted compressive pressure. Medical student surface closures were completed in under 3 minutes each, and are tabulated and recorded videographically. 40 human skin cancer excision wounds were closed via similar techniques in a Miami-based surgical practice, with pre- and post-operative photographs for presentation. Dehiscence, necrosis, infection incidence, and suturing times are tabulated.

Following buried suture placement, Syndaver in vitro 4x1 cm wounds were closed via the aforementioned surface cuticular suturing techniques in under 3 minutes. Surgical wounds in the case series showed no evidence of wound edge necrosis, dehiscence, or infection at 1, 7, 14, or 90 days postoperatively.

Suturing techniques minimizing forceps trauma, while preserving efficient suturing speed are presented herein. In vitro suturing with Syndaver abdominal plates videographically demonstrated the saline-based model’s teaching efficacy. A 40-patient case-series revealed no wound edge necrosis, dehiscence, or infections over follow-up, indicating the efficacy of the techniques. These findings suggest that speed and tissue preservation are not mutually exclusive in skin closures using the aforementioned techniques.

The inhomogeneous and not entirely objective analysis of sensibility in the context of free flap surgery limits our knowledge to such an extent that sensitized flaps are not (yet) the gold standard, although there is evidence that nerve coaptation in breast reconstruction using DIEP flaps leads to trauma prevention and a better quality of life. The aim of our pilot study was therefore to examine proteome analysis of flap skin to potentially detect molecular changes associated with denervation.

Skin biopsy samples from five patients from both abdominal (donor site) skin and DIEP flap skin were taken 6 months after breast reconstruction and examined using label-free quantitative proteomics profiling with a data-independent acquisition (DIA) strategy by liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS).

When combining the ten analysed samples, quantitative analysis revealed a total of 6109 protein groups, 72337 peptides and 103619 precursors, which were identified at 1% False discovery rates (FDR) for both precursor and protein group levels.
Dataset quality control showed acceptable results for an exploratory pilot study based on human skin biopsies. Replicates from both abdominal and breast flap skin samples tend to cluster together, indicating overall consistency within each condition. This observation was confirmed by a heat map, which shows clear clustering of several breast flap skin samples, whereas clustering among abdominal skin samples was less consistent.
In total, 452 proteins were found to be significantly modulated between abdominal and breast flap skin samples. Among them, 129 proteins were upregulated and 323 were downregulated in abdominal skin compared to breast flap skin.

Label-free quantitative proteomic profiling using DIA by LC-ESI-MS/MS was successfully performed on the ten analyzed skin biopsy samples. The high number of confidently identified protein groups (>6000) demonstrates the feasibility of DIA-based proteomic analysis on DIEP flaps. Quantitative proteomic analysis revealed differences in protein abundance between abdominal and breast flap skin.
These results provide a first molecular overview of the DIEP flap skin proteome and establish a reference dataset for our ongoing main study investigating proteomic changes in DIEP flaps for breast reconstruction with and without nerve coaptation.

Dermal substitutes are widely used to treat amongst other things full-thickness skin defects. However, to date comparative clinical data between animal-derived and fully synthetic matrices remain limited. This study aimed to compare Integra (r) Dermal Regeneration Template and NovoSorb (TM) Biodegradable Temporizing Matrix (BTM) regarding tissue generation, complications, split-thickness skin graft (STSG) take-rate, long-term outcomes and costs.

A single center retrospective cohort study was conducted including patients treated with Integra (r) or BTM between 2015 and 2025. Demographic characteristics, comorbidities, defect etiology and anatomical localization were recorded. Outcomes included matrix placement time from implantation to complete integration and removal of the temporary overlay layer, macroscopic quality of the generated tissue, complication rates, STSG take-rate, long-term healing results and product costs.

A total of 189 dermal substitutes were implanted in 157 patients (153 Integra (r), 36 BTM). BTM required a significantly longer placement time compared with Integra (r) (6 weeks vs 4 weeks). Integra (r) demonstrated superior macroscopic dermal-like tissue formation, whereas BTM predominantly generated granulation tissue. Seroma formation, maceration and matrix detachment occurred more frequently with Integra (r), while BTM was associated with a higher infection rate. No significant differences were observed between groups regarding reimplantation rate, STSG take or long-term healing outcomes. BTM was associated with substantially lower product costs.

Despite different integration characteristics and complication profiles, both matrices provide comparable clinical outcomes, supporting BTM as a safe and cost-effective synthetic alternative.

Autologous fat grafting is a common procedure in reconstructive and aesthetic surgery. Fat survival is the main clinical outcome and is critically influenced by a rapid and sufficient blood supply to the grafts, which best prevents volume loss due to resorption. In this study, we examined the role of fibroblast growth factor (FGF) 21, a hepatokine with metabolic and pro-angiogenic properties, in the revascularization process of white adipose tissue grafts.

Subcutaneous white adipose tissue from 4 FGF21-knockout (KO) mice and 4 C57BL/6J wild-type (WT) control mice was harvested and cut into small samples with standardized dimensions. These samples were transplanted into the dorsal skinfold chamber of matching FGF21-KO (n = 8) and WT (n = 8) recipient mice. The study monitored graft revascularization over 14 days using repeated intravital fluorescence microscopy and immunohistochemical analyses, including measurements of microhemodynamic parameters.

A delay in revascularization of FGF21-KO mice transplanted white adipose tissue was detected, as indicated by a significantly reduced perfused graft area starting at day 6 (2 ± 1 % vs. 13 ± 5 %), until the end of the experiment (87 ± 2 % vs. 98 ± 1 %) when compared to controls. This resulted in a significantly lower final functional microvessel density in either the peripheral (249 ± 11 cm/cm^2 vs. 361 ± 15 cm/cm^2) or central (248 ± 11 cm/cm^2 vs. 347 ± 16 cm/cm^2) regions of the grafts. Moreover, vessel maturation was equally impaired in FGF21-KO mice, as shown by the larger diameters of newly formed graft microvessels in the periphery of the grafts on day 14 (13.1 ± 0.3 microm vs. 11.7 ± 0.1 microm) and in the center (12.6 ± 0.2 microm vs. 11.2 ± 0.3 microm).
These findings were confirmed by immunohistochemical analyses, which showed a significantly lower microvessel density in the FGF21-KO group in comparison to controls (414 ± 29 mm^-2 vs. 539 ± 48 mm^-2)

Our findings suggest that FGF21 plays a pivotal role in white adipose tissue graft revascularization. Therefore, this hepatokine represents a promising target for the development of novel strategies to increase graft vascularization and consequent survival, thus, the clinical success rates of fat grafts.