Lymphatic Vessel-Mediated Attenuation of Persistent Macrophage Infiltration Improves Fat Grafting Outcomes in Mice Models.

BACKGROUND: Persistent macrophage infiltration may lead to adverse consequences, such as calcifications and nodules in fat grafts. Lymphatic vessels, which transport inflammatory cells, are involved in regulating inflammatory responses. Less is known, however, about lymphatic vessels after fat grafting. OBJECTIVES: The aim of this study was to explore the regulation of fat graft survival by lymphatic vessels. METHODS: A common adipose graft model was constructed to assess the processes responsible for changes in the number of lymphatic vessels in grafts. Adipose tissue samples from C57/BL6 mice and green fluorescent protein-expressing mice were cross-grafted to determine the source of lymphatic vessels. The number of lymphatic vessels in the grafts was increased by treatment with vascular endothelial growth factor C, and the effects of this increase on fat grafting were evaluated. RESULTS: The number of lymphatic vessels was greater in postgrafted fat than in inguinal fat before transplantation, with lymphatic vessels in these grafts gradually transitioning from donor to recipient sources. Lymphatic vessels grew more slowly than blood vessels during early stages of grafting; during later stages, however, the number of blood vessels declined markedly, with more lymphatic vessels than blood vessels being observed 60 days after grafting. Vascular endothelial growth factor C treatment increased graft lymphatics and distant volume retention, while reducing fibrosis and oil sacs. Lymphatic vessels acted as drainage channels for macrophages, with the degree of sustained macrophage infiltration decreasing with increases in the number of lymphatic vessels. CONCLUSIONS: Increasing the number of lymphatic vessels is beneficial for fat graft survival, which may be related to a reduction in prolonged macrophage infiltration.

Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration.

BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms.

Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell-cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell-cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.

Adipose Component Transplantation: An Advanced Fat-Grafting Strategy for Facial Rejuvenation.

BACKGROUND: Autologous fat grafting is frequently used for volume augmentation and tissue regeneration. The uniform physical and biological characteristics of fat grafts, however, limit their optimal effects in various situations. Subjecting fat tissue to different mechanical processes results in adipose-derived products with distinct biological components and physical features. The present study describes a novel facial fat-grafting strategy, adipose component transplantation (ACT), that yields different adipose products that can be applied to specific injection sites. METHODS: All patients who underwent ACT were evaluated retrospectively. Fat tissue samples were fractionated into high-density fat, adipose matrix complex, stromal vascular fraction gel, and adipose collagen fragment, as described. Each of these fractions was processed and injected into indicated recipient sites. Additional SVF gel was cryopreserved and, if necessary, injected during the following 3 months. Patients were followed up after 1, 2, 3, and 6 months, and annually thereafter. RESULTS: From March of 2020 to September of 2021, 78 patients underwent whole face fat grafting using the ACT strategy. All operations and secondary injections of cryopreserved SVF gel were uneventful. There were no major complications, and final aesthetic results were satisfactory in 91% of patients. CONCLUSIONS: The ACT strategy allows specific adipose products to be applied to specific injection sites, as warranted. Adipose matrix complex is indicated for sufficient rigid support, high-density fat when large volumes are required, SVF gel for precise injection and cryopreservation, and ACF as mesotherapy for skin rejuvenation. The ACT strategy optimizes the biological functions and physical features of different adipose-derived products. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Strategies for Constructing Tissue-Engineered Fat for Soft Tissue Regeneration.

BACKGROUND: Repairing soft tissue defects caused by inflammation, tumors, and trauma remains a major challenge for surgeons. Adipose tissue engineering (ATE) provides a promising way to solve this problem. METHODS: This review summarizes the current ATE strategies for soft tissue reconstruction, and introduces potential construction methods for ATE. RESULTS: Scaffold-based and scaffold-free strategies are the two main approaches in ATE. Although several of these methods have been effective clinically, both scaffold-based and scaffold-free strategies have limitations. The third strategy is a synergistic tissue engineering strategy and combines the advantages of scaffold-based and scaffold-free strategies. CONCLUSION: Personalized construction, stable survival of reconstructed tissues and functional recovery of organs are future goals of building tissue-engineered fat for ATE.

Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice.

Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagonist norBNI improved depressive-like behaviors and reversed PSD95, synaptophysin, p-ERK, p-CREB, and BDNF in NAc. This study demonstrated the important role of striatal KOR in morphine withdrawal-related depressive-like behaviors and offered therapeutic potential for the treatment of withdrawal-related depression.

New Insights and Advanced Strategies for In Vitro Construction of Vascularized Tissue Engineering.

Inadequate vascularization is a significant barrier to clinical application of large-volume tissue engineered grafts. In contrast to in vivo vascularization, in vitro prevascularization shortens the time required for host vessels to grow into the graft core and minimizes necrosis in the core region of the graft. However, the challenge of prevascularization is to construct hierarchical perfusable vascular networks, increase graft volume, and form a vascular tip that can anastomose with host vessels. Understanding advances in in vitro prevascularization techniques and new insights into angiogenesis could overcome these obstacles. In the present review, we discuss new perspectives on angiogenesis, the differences between in vivo and in vitro tissue vascularization, the four elements of prevascularized constructs, recent advances in perfusion-based in vitro prevascularized tissue fabrication, and prospects for large-volume prevascularized tissue engineering.

Ultra-condensed Fat: A Novel Fat Product for Volume Augmentation.

BACKGROUND: Fat transplantation retention rate is individualized and unpredictable. The presence of blood components and oil droplets in the injected lipoaspirate increases inflammation and fibrosis in a dose-dependent manner, and is probably the key factor associated with poor retention. OBJECTIVES: This study describes a volumetric fat grafting strategy based on optimization of grafts via screening intact fat particles and absorbing free oil droplets and impurities. METHODS: Centrifuged fat components were analyzed by n-hexane leaching. A special device was applied to de-oil intact fat components and obtain ultra-condensed fat (UCF). UCF was evaluated by scanning electron microscopy, particle size analysis, and flow cytometric analysis. Histological and immunohistochemical changes were investigated in a nude mouse fat graft model over 90 days. RESULTS: The lower 50% of centrifuged fat was concentrated to 40% of the original volume to obtain UCF. In UCF, the free oil droplet content was less than 10%, more than 80% of particles were larger than 1000 µm, and architecturally important fat components were present. The retention rate of UCF was significantly higher than that of Coleman fat on day 90 (57.5 ± 2.7% vs. 32.8 ± 2.5%, p < 0.001). Histological analysis detected small preadipocytes with multiple intracellular lipid droplets on day 3 in UCF grafts, indicative of early adipogenesis. Angiogenesis and macrophage infiltration were observed in UCF grafts soon after transplantation. CONCLUSION: Adipose regeneration with UCF involves rapid macrophage infiltration and exit, resulting in angiogenesis and adipogenesis. UCF may serve as a lipofiller which is beneficial for fat regeneration. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Endogenous Bone Marrow-Derived Stem Cell Mobilization and Homing for In Situ Tissue Regeneration.

In mammals, post-injury repair and regenerative events rely predominantly on stem cell function. Stem cell transplantation has achieved considerable success in animals but remains unfavorable for humans because of the unavoidable drawbacks. Nevertheless, substantial evidence suggests the regenerative potential of endogenous stem cells can be improved for functional and structural recovery of tissue damage or in disease conditions. Endogenous stem cells are mostly quiescent under steady-state conditions and reside in their niche. Once faced with tissue injury, physiological and molecular changes within the niche or from distant tissues activate the migration, proliferation, and differentiation of stem cells, contributing to tissue repair. Tissue regeneration is augmented by artificially amplifying the factors that promote stem cell mobilization or enhance the homing of endogenous stem cells. This cell-free strategy, known as "in situ tissue regeneration," represents a safer and more efficient means to conduct tissue regeneration. Bone marrow (BM) is considered the central niche and main reservoir of many types of stem cells. These stem cells hold great therapeutic potential for the regeneration of multiple injured tissues. Herein, we review recent strategies for promoting in situ tissue regeneration through BM-derived stem cell mobilization or homing in animal models as well as in human trials. With the advancement in biomaterial engineering, chemoattractant signals combined with functionalized bioscaffolds have accomplished sustained activation of endogenous BM-derived stem cells that can be used as an attractive strategy for efficient in situ tissue regeneration.

Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration.

Background: Large-area soft tissue defects are challenging to reconstruct. Clinical treatment methods are hampered by problems associated with injury to the donor site and the requirement for multiple surgical procedures. Although the advent of decellularized adipose tissue (DAT) offers a new solution to these problems, optimal tissue regeneration efficiency cannot be achieved because the stiffness of DAT cannot be altered in vivo by adjusting its concentration. This study aimed to improve the efficiency of adipose regeneration by physically altering the stiffness of DAT to better repair large-volume soft tissue defects. Methods: In this study, we formed three different cell-free hydrogel systems by physically cross-linking DAT with different concentrations of methyl cellulose (MC; 0.05, 0.075 and 0.10 g/ml). The stiffness of the cell-free hydrogel system could be regulated by altering the concentration of MC, and all three cell-free hydrogel systems were injectable and moldable. Subsequently, the cell-free hydrogel systems were grafted on the backs of nude mice. Histological, immunofluorescence and gene expression analyses of adipogenesis of the grafts were performed on days 3, 7, 10, 14, 21 and 30. Results: The migration of adipose-derived stem cells (ASCs) and vascularization were higher in the 0.10 g/ml group than in the 0.05 and 0.075 g/ml groups on days 7, 14 and 30. Notably, on days 7, 14 and 30, the adipogenesis of ASCs and adipose regeneration were significantly higher in the 0.075 g/ml group than in the 0.05 g/ml group (p < 0.01 or p < 0.001) and 0.10 g/ml group (p < 0.05 or p < 0.001). Conclusion: Adjusting the stiffness of DAT via physical cross-linking with MC can effectively promote adipose regeneration, which is of great significance to the development of methods for the effective repair and reconstruction of large-volume soft tissue defects.

Fascia Promotes Adipose Tissue Regeneration by Improving Early Macrophage Infiltration after Fat Grafting in a Mouse Model.

BACKGROUND: Low early macrophage fat graft infiltration (within a week of surgery) hinders tissue regeneration, suggesting that macrophages play a vital role in early angiogenesis and adipogenesis. However, the source of macrophages during this period is unclear. METHOD: C57BL/6 mice were split into fascial removal (FR) group and control groups (CG). Mice had a piece of back fascia removed in the FR group, which was immediately replaced in the CG, and inguinal fat injected into the transplantation site of both groups. Separately, fascia was harvested from green fluorescent protein-expressing mice and transplanted into C57BL/6 mice for tracing macrophage infiltration after fat grafting. RESULTS: The number of capillaries in the FR group was lower than that in the CG at days 3 ( P < 0.01) and 7 ( P < 0.05). Moreover, the number of small adipocytes in the FR group was lower than in the CG on days 3, 7, and 14 (all P < 0.05), and the relative expression of several adipogenic proteins was significantly lower in the FR group than in the CG on days 14 and 30. The timeline of macrophage infiltration was consistent with angiogenesis and adipogenesis. The number of macrophages in the FR group was significantly lower than in the CG at days 3 and 7 ( P < 0.05), and there were more fascia-derived macrophages than circulation-derived macrophages infiltrated into fat grafts within 7 days. Finally, the graft retention was lower in the FR group than the CG at day 90 ( P < 0.05). CONCLUSION: In the early stage after fat grafting, fascial macrophage infiltration initiates tissue regeneration, thereby improving graft retention by promoting angiogenesis and adipogenesis. CLINICAL RELEVANCE STATEMENT: In the clinic, injecting fat close to the fascia may increase fat retention. Fascia is widespread and self-regenerating, which may be a promising alternative source of local macrophages, with implications for tissue-engineering therapies such as correction of soft-tissue defects and breast reconstruction.

Early Angiogenesis-Dependent CXCL12 Attracts Adipose-Derived Stem Cells to Promote the Repair of Fat Grafting in a Mouse Model.

BACKGROUND: The unpredictable and unstable tissue retention rate of autologous fat grafting remains an obstacle faced by plastic surgeons. The authors' previous study using a fat grafting mouse model with donor sites showed that adipose-derived stem cell (ASC) infiltration in the recipient site was delayed, leading to poor regeneration and lower retention. Thus, the mechanism behind the differential infiltration of ASCs needed to be explored. METHODS: First, the authors locally injected C-X-C chemokine ligand 12 (CXCL12) or C-X-C motif chemokine receptor 4 (CXCR4) inhibitor AMD3100 in the recipient or donor site, respectively (CXCL12 + AMD3100 - , CXCL12 - AMD3100 + , and CXCL12 + AMD3100 + groups). The authors compared the migration of ASCs, adipose regeneration, and long-term retention. Next, the authors explored the role of angiogenesis using a normal/ischemic mice model in which the authors test the expression of CXCL12/CXCR4, migration of ASCs, and adipose regeneration. RESULTS: Blocking CXCL12 in the donor site using AMD3100 (CXCL12 - AMD3100 + and CXCL12+AMD3100+ groups) could accelerate ASC infiltration and promote adipose regeneration and long-term retention ( P < 0.05) compared with the other groups. CXCL12 and its receptor CXCR4 were more highly expressed in normal than in ischemic adipose tissue; consistently, there were more ASCs infiltrating normal than ischemic adipose tissue early after surgery ( P < 0.05). CONCLUSION: Early angiogenesis is essential for CXCL12 in promoting ASC infiltration, improving adipose tissue repair in the recipient site, and potentiating the long-term fat retention rate. CLINICAL RELEVANCE STATEMENT: The authors provide a proof-of-concept way to improve the outcomes of fat grafting by locally injecting AMD3100, also known as plerixafor, to the donor site.

Mechanical Force Directs Proliferation and Differentiation of Stem Cells.

Stem cells have attracted much attention in the field of regeneration due to their unique ability to promote regeneration. Among the many approaches used to regulate directed proliferation and differentiation of stem cells, application of mechanical forces is safe, simple, and easy to implement, all of which are advantageous to practical applications. In this review, the mechanisms of mechanical regulation of stem cell proliferation and differentiation are summarized with emphasis on force transduction pathways from the extracellular matrix to the nucleus. Prospects for future clinical applications are also discussed. In conclusion, through specific signaling pathways, mechanical signals ultimately affect gene expression and thus guide cell fate. Mechanical factors can regulate proliferation and differentiation of stem cells through signaling pathways, a greater understanding of which will contribute to future research and applications of cell regeneration therapy. Impact statement Mechanical mechanics is vital for the regulation of cell fate; especially in the field of regenerative medicine, mechanical control has characteristics that are simple and comparable. Mechanically regulated pathways exist widely in cells and are distributed at various structural levels of cells. In this review, we categorized the mechanical regulatory pathways through the clue of the mechanical transmission. We tried to include some newly researched pathways, such as Piezo-related pathways, to show the recent vigorous development in this field.

Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model.

Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis arising during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Therefore, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. Besides, CD4+ T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (ASCs-CM) in vitro. We detected the ratio of Th2%/Th1%. Results showed that the retention rate was higher in 104 group, while even lower in 108 group with significantly increased inflammation and fibrosis than control group at week 12 in vivo. There was no significance between control group and 106 group. Also, 108 group increased the infiltration of M2 macrophages, CD4+ T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by ASCs-transwell group was higher than ASCs-CM group and showed concentration-dependent. Accordingly, high concentrations of ASCs in adipose tissue can promote Th1-Th2 shifting, and excessive Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. Also, we found ASCs promoted Th1-Th2 shifting in vitro.

The therapeutic effect of adipose-derived stem cells on soft tissue injury after radiotherapy and their value for breast reconstruction.

BACKGROUND: Postmastectomy radiotherapy is considered to be a necessary treatment in the therapy of breast cancer, while it will cause soft tissue damage and complications, which are closely related to the success rate and effectiveness of breast reconstruction. After radiotherapy, cutaneous tissue becomes thin and brittle, and its compliance decreases. Component fat grafting and adipose-derived stem cell therapy are considered to have great potential in treating radiation damage and improving skin compliance after radiotherapy. MAIN BODY: In this paper, the basic types and pathological mechanisms of skin and soft tissue damage to breast skin caused by radiation therapy are described. The 2015-2021 studies related to stem cell therapy in PubMed were also reviewed. Studies suggest that adipose-derived stem cells exert their biological effects mainly through cargoes carried in extracellular vesicles and soluble secreted factors. Compared to traditional fat graft breast reconstruction, ADSC therapy amplifies the effects of stem cells in it. In order to obtain a more purposeful therapeutic effect, proper stem cell pretreatment may achieve more ideal and safe results. CONCLUSION: Recent research works about ADSCs and other MSCs mainly focus on curative effects in the acute phase of radiation injury, and there is little research about treatment of chronic phase complications. The efficacy of stem cell therapy on alleviating skin fibrosis and its underlying mechanism require further research.

Three-Dimensional Culture Promotes Secretion of Extracellular Matrix Structure Fat Flap with Lipoaspirates in Vitro.

Adipose tissue engineering represents a possible solution for large-volume soft-tissue reconstruction. Although there have been several reports on the construction of tissue-engineered fat (TEF) flaps in vivo and in vitro, each condition has various limitations. Thus, we developed a novel approach for engineering fat tissue using a three-dimensional culture system. We used different volumes of lipoaspirates to fill the same tissue engineering chamber (30%, 50%, 80%, and 100% volume/space ratio) for different periods (3, 5, 7, and 14 days) to determine whether lipoaspirates can form structural fat tissue in vitro. We then studied the histological structure and extracellular matrix (ECM) of the tissue formed in vitro. We selected engineering tissue-like fat of the 80% volume/space ratio group cultured for 7 days to be subcutaneously implanted into mice for up to 3 months, and lipoaspirates without structure in vitro were used as a control. The lipoaspirates from the 80% volume/space ratio group cultured in vitro formed TEF-like tissue, which increased in small adipocytes and ECM with time until becoming stable on day 7. The live/dead test showed that the tissue cultured in vitro remained viable until day 7. Immunofluorescence staining results revealed that the collagen I and IV content increased over time. Moreover, after grafting, "self-assembly" fat had higher volume retention, better vascularization, fewer oil droplets, and less fibrosis than the lipoaspirates without structure in vitro. Therefore, our results demonstrate that lipoaspirates filled in tissue engineering chamber can be cultured in vitro and can "self-assemble" into TEF-like tissue. Furthermore, the "self-assembly" fat tissue produced better grafting results than those of lipoaspirates without structure in vitro.

Density-Based High-Quality Fat: Characterization and Correlation with Different Body Fat Ratio.

BACKGROUND: Lipoaspirate can be divided into high-quality fat and low-quality fat using Coleman's centrifugation by adding 0.935 g/ml marker float; the ratio obtained by different individuals is different. OBJECTIVES: This study aimed to examine the HQF obtained from different individuals and establish the relationship between individual body data and HQF. METHODS: We used Coleman's centrifugation method (1200 g, 3 min) with 0.935 g/ml density float to process lipoaspirate and collect HQF from different individuals for the analysis of fat characteristics and in vivo grafting. RESULTS: The HQF obtained from different individuals had similar stromal vascular fraction cell numbers and extracellular matrix content. In animal experiments at different time points (especially 12 weeks), the appearance, retention rate, hematoxylin and eosin staining, and immunohistochemistry results of HQF grafts were similar, while being different from those of Coleman fat. The HQF obtained from individuals with higher body fat ratio was less than those with lower body fat ratio. Following the establishment of the relationship between high-quality fat percentage and the body fat ratio of the donors, we proposed an innovative calculation formula model for the required lipoaspirate. CONCLUSIONS: HQF obtained from different individuals has similar fat characteristics, transplantation process, and outcome. The HQF percentage obtained from different individuals is negatively correlated with the body fat ratio. The amount of liposuction can be predicted using the proposed formula and improve the predictability of fat transplantation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis.

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host-derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long-term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro-Grafting) group was engrafted with prepared fat (0.3 ml). The pro-Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 106 GFP+M0 macrophages, and then, 2 ng IL-4 was injected into the grafts on Day 3. In addition, 1.0 × 106 GFP+M0 macrophages were injected into the tail vein for tracing in the Pro-Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro-Grafting group. The long-term retention rate was higher in the Pro-Grafting+M2 group (52% ± 6.5%) than in the Pro-Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR-γ, C/EBP and AP2 was higher in the Pro-Grafting+M2 group than in the Pro-Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.

Adipose matrix complex: a high-rigidity collagen-rich adipose-derived material for fat grafting.

Due to the low percentage of collagen, the rigid support capacity of fat grafts remains unsatisfactory for some clinical applications. In this study, we evaluated a strategy in which adipose matrix complex (AMC) was collected via a mechanical process and transplanted for supportive filling of the face. Our AMC samples were collected from adipose tissue by a filter device consisting of a sleeve, three internal sieves, and a filter bag (100 mesh). AMC derived from adipose tissue had fewer cells than Coleman fat, but much higher levels of collagen and stiffness. Retention rates 90 days after transplantation in nude mice were higher for AMC than for Coleman fat (75±7.5% vs. 42±13.5%; P < 0.05). In addition, AMC maintained a higher stiffness (~6 kPa vs. ~2 kPa; P < 0.01) and stably retained a higher level of collagen. Our findings demonstrate that mechanical collection of AMC from adipose tissue is a practical method for improving fat graft retention and rigid support. This strategy has the potential to improve the quality of lipoaspirates for patients requiring rigid supportive filling.