The Optimal Layer for Breast Augmentation in an Autologous Fat Grafting Murine Model.

BACKGROUND: Fat grafting is an effective procedure for breast augmentation, but the variations in this technique result in unpredictable fat retention. Therefore, animal models are needed to simulate the operation and the optimal layer for fat retention. OBJECTIVES: An autologous fat grafting murine model for breast augmentation was built to detect a new layer for fat grafting in the chest. METHODS: The left side of the female rat inguinal fat flap was harvested, dissected into small pieces, and autotransplanted into 3 different layers of the breast. Retention rate and hematoxylin and eosin (H&E) staining were measured at 1, 4, 8 12, and 16 weeks. Immunofluorescence staining was utilized to detect adipocytes and endothelial cells, and immunohistochemistry was conducted to evaluate the expression of integrins ß1 and α6. RESULTS: The volume of fat grafts slightly grew in the intramuscular and submuscular layers at Week 4. Retention rates in the subcutaneous layer and submuscular layer were significantly higher than the intramuscular layer at Week 16. H&E staining showed that oil cysts existed in the subcutaneous layer throughout the 16 weeks. At the terminal time point, well-vascularized mature adipose structures were observed in intramuscular and submuscular layers, with smaller adipocytes in intramuscular layers. Immunohistochemistry analysis showed that integrin ß1 was identically expressed in every adipocyte in all the layers, whereas integrin α6 selectively expressed in bigger adipocytes in the intramuscular layer. The expression intensities of integrin ß1 and α6 were significantly higher in the intramuscular layer than in the subcutaneous and submuscular layers. CONCLUSIONS: The angiogenic and moderate mechanical environment makes the submuscular layer the optimal layer for fat retention.

Particles of Different Sizes Affect the Retention Pattern of the Fat Grafts in a Mouse Model.

BACKGROUND: Autologous fat grafting is an effective form of soft tissue regeneration. However, the optimal fat particle size and graft retention pattern need more research. METHODS: The mouse inguinal fat pad was harvested and cut into fat particles of different diameters: ≥ 5 mm, 3-4 mm, 2-3 mm, 1-2 mm and 1 mm (micro-fat). A volume of 0.2 ml fat was transplanted into another mouse dorsum. Volume and retention rate were measured at 1, 4, 8 and 12 weeks. Histology analysis was performed. Immunofluorescence staining was used to evaluate M1 and M2 macrophage infiltration and graft angiogenesis. RESULTS: Fat retention was highest in the "> 5 mm" group and lowest in the "micro-fat" group. Large vacuoles were more common in larger-diametered fat particles. There was less collagen accumulation in the well-vascularized connective tissue in the "1-2 mm" group. The infiltrated nucleated cells peak at week 4 in groups of fat particles under 3 mm and at week 8 in in groups with fat particles above 3 mm. The number of M1 macrophages peaked at week 1 and then declined in all groups except for the "5 mm" group. The number of M2 macrophages peaked at week 4 and gradually decreased through 12 weeks in the groups below 3 mm, but increased through 12 weeks in the groups above 3 mm. Vascular intensity was similar to M2 macrophage prevalence. CONCLUSIONS: Fat particles of different sizes may posses different retention patterns. Larger grafts have higher retention rate but worse quality. Meanwhile, smaller grafts have better quality with lower retention rate. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Decellularized extracellular matrix (d-ECM): the key role of the inflammatory process in pre-regeneration after implantation.

Clinical medicine is encountering the challenge of repairing soft-tissue defects. Currently, natural and synthetic materials have been developed as natural scaffolds. Among them, the decellularized extracellular matrix (d-ECM) can achieve tissue remodeling following injury and, thus, replace defects due to its advantages of the extensiveness of the source and excellent biological and mechanical properties. However, by analyzing the existing decellularization techniques, we found that different preparation methods directly affect the residual components of the d-ECM, and further have different effects on inflammation and regeneration of soft tissues. Therefore, we analyzed the role of different residual components of the d-ECM after decellularization. Then, we explored the inflammatory process and immune cells in an attempt to understand the mechanisms and causes of tissue degeneration and regeneration after transplantation. In this paper, we summarize the current studies related to updated protocols for the preparation of the d-ECM, biogenic and exogenous residual substances, inflammation, and immune cells influencing the fate of the d-ECM.

Nanocellulose incorporated oleogel matrix for controlled-release of active ingredients in the lower gastrointestinal tract.

Controlled release is often preferred for orally administrated bioactive compounds and drugs. In this study, a nanocellulose (NC) incorporated oleogel encapsulation system was developed for controlled release of active agents. 5-Aminosalicylic acid (5-ASA), an anti-inflammatory drug to treat inflammatory bowel diseases, was used as an example core ingredient for demonstrating the efficacy of the system. Oleogels with/without NC incorporation encapsulating 5-ASA were prepared and tested by in vitro digestion study, and 5-ASA released from the matrix was quantified by a novel UV-Vis spectrometric method developed in this study. The oleogel encapsulation system was characterized by assessing the encapsulation efficiency, oxidative stability, gel hardness, microstructure, and thermal stability. Results showed that sorbitan tristearate-induced oleogel system successfully protected 5-ASA during GI digestion. The incorporation of NC solutions with different NC types, concentrations and volumes further modified the release rate. Specifically, the release of 5-ASA in NC incorporated matrix was <6 % in the gastric phase, and ranged between 17.42 % - 38.28 % in the small intestine depending on the added NC type and concentration. Additionally, the incorporation of NC improved physicochemical stability of the gel matrix. The new 5-ASA quantification method developed in this study is simpler and faster compared with currently available methods.

Efficacy and Safety of External Volume Expansion (EVE) on Fat Grafting: A Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: The autologous fat grafting is commonly used for reconstructive or aesthetic purposes. However, due to the huge variation in methods, its retention rate varies a lot. External volume expansion (EVE) has been used to treat recipient sites of fat grafting. Concerns have been raised regarding its efficacy and safety. METHODS: We have searched PubMed, EMBASE, and the Cochrane Library for studies on EVE-assisted fat grafting published from 2000 to 2020. A meta-analysis was conducted to pool the retention rate. The incidence of complications was assessed for reconstructive or aesthetic purposes. RESULTS: The 11 included studies involved 1152 patients with operations on 1794 breasts. Four studies were included in the meta-analysis. The pooled retention rate was 65% [95%CI 49, 79]. Eight studies reported the complications. The total complication incidence was 34%, which is 35% for the aesthetic group and 33% for the reconstructive group. The complication rate was not obviously different between the two groups. CONCLUSIONS: The study shows that the EVE-assisted fat grafting has better retention rate than traditional fat grafting. However, the data showed that the complication rate was much higher in the EVE-assisted group.

Influence of cellulose nanocrystals (CNC) on permeation through intestinal monolayer and mucus model in vitro.

Cellulose nanocrystals (CNC) as a novel ingredient in foods and pharmaceuticals still lacks the safety and functionality information. We aimed to assess the absorption of CNC in small intestine and the effect on cell viability. In the second part, the impact of CNC on substance permeation through mucus layer, including the potential functionality in improving high blood cholesterol, was tested. No noticeable amount of CNC was found to penetrate through differentiated Caco-2 monolayer and in vitro mucus layer, and CNC had low toxicity on Caco-2 cell viability up to 10 mg/mL. CNC at 2 % (w/w) may affect the permeability of the mucus layer and larger molecules are more easily influenced. CNC may also alleviate hypercholesteremia by increasing viscosity of digesta, adsorbing cholesterol, and decreasing bile acids permeation. The results suggest CNC may not penetrate the small intestinal lining and may be used as a functional supplement.

Biocompatible Interface-Modified Tissue Engineering Chamber Reduces Capsular Contracture and Enlarges Regenerated Adipose Tissue.

Adipose flap expansion using a tissue engineering chamber (TEC) presents a promising candidate for soft tissue regeneration by activating in situ adipose tissue regeneration. However, foreign body reaction (FBR) and capsular contracture caused by a silicone chamber limit large tissue reconstruction. Here, a hydrophilic and biodegradable film made of poly(ethylene glycol) diacrylate (PEG-da) with methacrylated gelatin (gelatin-MA) was presented between the host tissue and silicone chamber to tune the local wound and to prevent initiation of FBR. After a 60 day investigation, 6.1-fold-regenerated fat tissue was obtained from the PEG-gelatin group, whereas only 3-fold tissue was harvested from a silicone group. Histological staining demonstrated that the structure of the neo-formed adipose tissue in both groups was similar to mature adipose tissue. Noticeably, a more distinct and denser fibrous capsule was observed in the silicone group compared to the PEG-gelatin group. Immunohistochemistry of CD206 and TGF-ß expression indicated less M2 macrophage infiltration and a minor inflammation reaction with PEG-gelatin assistance. Less collagen deposition and myofibroblast activation in the PEG-gelatin group were demonstrated via α-SMA and type I collagen staining. All these demonstrated that a biocompatible membrane supplement can attenuate capsule formation and contracture leading to a larger tissue regeneration through the TEC technique, which could lead to new perspectives to the relationship between materials-mattered FBR and tissue regeneration.

External Volume Expansion Up-Regulates CXCL12 Expression and Enhances Mesenchymal Stromal Cell Recruitment toward Expanded Prefabricated Adipose Tissue in Rats.

BACKGROUND: External volume expansion devices are effective for adipose tissue regeneration. However, the detailed mechanisms by which external volume expansion devices induce adipose tissue regeneration remain unclear. METHODS: An external volume expansion device was used to construct expanded prefabricated adipose tissue in a rat model. CXCL12 levels in local exudate and serum were measured by enzyme-linked immunosorbent assay, and CXCL12 expression in adipose tissue was assessed immunohistochemically. Fluorescent dye (CM-DiI)-labeled bone marrow-derived mesenchymal stromal cells and labeled mesenchymal stromal cells pretreated with the CXCR4 antagonist AMD3100 were transplanted into rats and tracked in vivo by fluorescence imaging. RESULTS: CXCL12 levels in local exudate and serum peaked 2 and 7 days, respectively, after external volume expansion device application. CXCL12 cell counts were significantly higher in the external volume expansion than in the control group. These CXCL12 cells were mainly columnar or cuboidal and began to express peroxisome proliferator-activated receptor γ on day 9. CM-DiI-labeled mesenchymal stromal cells were successfully recruited to the expanded prefabricated adipose tissue, a process partly inhibited by the CXCR4 antagonist AMD3100. These recruited CM-DiI-labeled mesenchymal stromal cells were found among the CXCL12 columnar cells. CONCLUSIONS: External volume expansion devices enhance CXCL12 expression levels, especially in columnar and cuboidal cells. The CXCL12/CXCR4 pathway is involved in recruiting circulating mesenchymal stromal cells to participate in adipose regeneration. These findings may reveal the mechanism underlying external volume expansion and provide insights into the refinement of these devices.