Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy

Background: The applications for fat grafting have increased recently, within both regenerative and reconstructive surgery. Although fat harvesting, processing and injection techniques have been extensively studied and standardised, this has not had a big impact on the variability of outcome following fat grafting. This suggests a possible larger role of patient characteristics on adipocyte and adipose-derived stem cell (ADSC) viability and function. This systematic review aims to collate current evidence on the effect of patient factors on adipocyte and ADSC behaviour. Methods: A systematic literature review was performed using MEDLINE, Cochrane Library and EMBASE. It includes outcomes observed in in vitro analyses, in vivo animal studies and clinical studies. Data from basic science work have been included in the discussion to enhance our understanding of the mechanism behind ADSC behaviour. Results: A total of 41 papers were included in this review. Accumulating evidence indicates decreased proliferation and differentiation potential of ADSCs with increasing age, body mass index, diabetes mellitus and exposure to radiotherapy and Tamoxifen, although this was not uniformly seen across all studies. Gender, donor site preference, HIV status and chemotherapy did not show a significant influence on fat retention. Circulating oestrogen levels have been shown to support both adipocyte function and graft viability. Evidence so far suggests no significant impact of total cholesterol, hypertension, renal disease, physical exercise and peripheral vascular disease on ADSC yield. Conclusions: A more uniform comparison of all factors highlighted in this review, with the application of a combination of tests for each outcome measure, is essential to fully understand factors that affect adipocyte and ADSC viability, as well as functionality. As these patient factors interact, future studies looking at adipocyte viability need to take them into consideration for conclusions to be meaningful. This would provide crucial information for surgeons when deciding appropriate volumes of lipoaspirate to inject, improve patient selection, and counsel patient expectations with regards to outcomes and likelihood for repeat procedures. An improved understanding will also assist in identification of patient groups that would benefit from graft enrichment and cryopreservation techniques

Development of a Tissue-Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema

Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P < 0.001), favorable kink resistance, and excellent suture retention property (casted vs. coagulated, P < 0.05). Cytocompatibility study showed that the POSS-PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue-engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema

Mechanical and surface chemical analysis of retrieved breast implants from a single centre

INTRODUCTION: Breast implants are associated with complications such as capsular contracture, implant rupture and leakage often necessitating further corrective surgery. Re-operation rates have been reported to occur in up to 15.4% of primary augmentation patients and up to 27% in primary reconstructions patients within the first three years (Cunningham, 2007). The aim of this study was to examine the mechanical and surface chemical properties as well as the fibroblast response of retrieved breast implants in our unit to determine the in vivo changes which occur over time. METHODS: Ethical approval was obtained. 47 implants were retrieved. Implantation time ranged from 1 month to 388 months (Mean 106.1 months). Tensile strength, elongation, Young's modulus and tear strength properties were measured using Instron 5565 tensiometer on anterior and posterior aspects of the implant. Attenuated total reflectance-fourier transform infra-red spectroscopy (ATR-FTIR), wettability and scanning electron microscopy (SEM) analysis was performed on the shell surfaces. Bicinchoninic acid assay was performed to determine shell protein content. The fibroblast response was determined by seeding HDFa cells on the retrieved implants and cell metabolism measured using Alamar Blue™ assay. RESULTS: Mechanical properties fall with increasing duration of implantation. There were no significant changes in ATR-FTIR spectra between ruptured and intact implants nor significant changes in wettability in implants grouped into 5 year categories. SEM imaging reveals surface degradation changes with increasing duration of implantation. CONCLUSIONS: With increasing duration of implantation, mechanical properties of the breast implants fall. However this was not associated with surface chemical changes as determined by ATR-FTIR and wettability nor protein content of the shells. Thus the reduction in mechanical properties is associated with breast implant failure but further research is required to elucidate the mechanisms

Fat grafting and platelet-rich plasma in wound healing: a review of histology from animal studies

Stem cells could form the basis of a novel, autologous treatment for chronic wounds like diabetic foot ulcers. Fat grafts contain adipose-derived stem cells (ADSC) but low survival of cells within the grafts is a major limitation. Platelet-rich plasma (PRP) may increase graft survival. This review examines the histology from animal studies on fat grafting, ADSC and PRP in wound healing. A literature review of major electronic databases was undertaken, and narrative synthesis performed. Data from 30 animal studies were included. ADSC increase angiogenesis over 14 days and often clinically accelerated wound healing. ADSC had a greater effect in animals with impaired wound healing (e.g. diabetes). Activated PRP increased viability of fat grafts. Despite the high number of studies, the quality is variable which weakens the evidence. It does suggest there is a benefit of ADSC, particularly in impaired wound healing. High-quality evidence in humans is required, to establish its clinical usefulness

A Systematic Review of Autologous Fat Grafting in the Treatment of Acute and Chronic Cutaneous Wounds

BACKGROUND: There is a growing interest in the regenerative potential of autologous fat. Adipose-derived stem cells, within the stromal vascular fraction of lipoaspirate samples, demonstrate anti-inflammatory, immunomodulatory, and angiogenic properties. This systematic review aimed to determine the efficacy and safety of autologous fat therapies for wound healing, with an evaluation of the quality of evidence provided by the literature. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched Ovid Medline, Embase, and Cochrane Library databases from inception to November 2018. We included all human studies where wounds were treated with lipotransfer, cell-assisted lipotransfer, stromal vascular fraction products, or isolated adipose-derived stem cells. Study screening and data extraction were performed by 2 authors. The quality of evidence was evaluated using the GRADE approach. RESULTS: The search strategy returned 5027 citations. From these, 10 observational case series were included in the qualitative synthesis; there were no randomized controlled trials. Patient characteristics, wound etiology, and intervention type differed markedly between studies, precluding formal meta-analysis. Autologous fat grafting was associated with satisfactory wound healing in all studies with low complication rates. However, the quality of evidence was consistently very low. CONCLUSIONS: Autologous fat grafting is an emerging therapeutic option for challenging wounds, although there is insufficient evidence to conclusively demonstrate its effectiveness and adverse event profile. Based on the literature to date, it is unclear whether one type of autologous fat therapy is superior. Well-designed, blinded, prospective randomized controlled trials with adequate methodologic details and objective outcome measure reporting are essential. PROSPERO ID: CRD42017081499

The current progress and critical analysis of three-dimensional scanning and three-dimensional printing applications in breast surgery.

BACKGROUND: Several attempts have been made to develop a tool capable of evaluating breast shape and volume to aid surgical planning and outcome assessment. More recently, newer technologies such as three-dimensional (3D) scanning and 3D printing have been applied in breast assessment. The aim of this study was to review the literature to assess the applicability of 3D scanning and 3D printing in breast surgery. METHODS: A literature search was carried on PubMed, Google Scholar and OVID from January 2000 to December 2019 using the keywords '3D', 'Three-dimensional', 'Three/four dimensions' and 'Breast'. RESULTS: A total of 6564 articles were identified initially; the abstracts of 1846 articles were scanned, and 81 articles met the inclusion criteria and were included in this review. Articles were reviewed and classified according to their aims, study subjects, the software and hardware used, main outcomes and major limitations. CONCLUSIONS: These technologies are fast and easy to use, however, high costs, long processing times and the need for training might limit their application. To incorporate these technologies into standard healthcare, their efficacy and effectiveness must be demonstrated through multiple and rigorous clinical trials

An evaluation of the bacteriostatic effect of platelet-rich plasma

Chronic wounds are a considerable health burden with high morbidity and poor rates of healing. Colonisation of chronic wounds by bacteria can be a significant factor in their poor healing rate. These bacteria can develop antibiotic resistance over time and can lead to wound infections, systemic illness, and occasionally amputation. When a large number of micro‐organisms colonise wounds, they can lead to biofilm formation, which are self‐perpetuating colonies of bacteria closed within an extracellular matrix, which are poorly penetrated by antibiotics. Platelet‐rich plasma (PRP) is an autologous blood product rich in growth factors and cytokines that are involved in an inflammatory response. PRP can be injected or applied to a wound as a topical gel, and there is some interest regarding its antimicrobial properties and whether this can improve wound healing. This study aimed to evaluate the in vitro bacteriostatic effect of PRP. PRP was collected from healthy volunteers and processed into two preparations: activated PRP—activated with calcium chloride and ethanol; inactivated PRP. The activity of each preparation against Staphylococcus aureus and Staphylococcus epidermis was evaluated against a control by three experiments: bacterial kill assay to assess planktonic bacterial growth; plate colony assay to assess bacterial colony growth; and colony biofilm assay to assess biofilm growth. Compared with control, both preparations of PRP significantly inhibited growth of planktonic S aureus and S epidermis. Activated PRP reduced planktonic bacterial concentration more than inactivated PRP in both bacteria. Both PRP preparations significantly reduced bacterial colony counts for both bacteria when compared with control; however, there was no difference between the two. There was no difference found between biofilm growth in either PRP against control or against the other preparation. This study demonstrates that PRP does have an inhibitory effect on the growth of common wound pathogens. Activation may be an important factor in increasing the antimicrobial effect of PRP. However, we did not find evidence of an effect against more complex bacterial colonies

Histological analysis of fat grafting with platelet-rich plasma for diabetic foot ulcers—A randomised controlled trial

Diabetic foot ulcers are often unresponsive to conventional therapy and are a leading cause of amputation. Animal studies have shown stem cells and growth factors can accelerate wound healing. Adipose-derived stem cells are found in fat grafts and mixing them with platelet-rich plasma (PRP) may improve graft survival. This study aimed to establish the histological changes when diabetic foot ulcers are treated with fat grafts and PRP. A three-armed RCT was undertaken of 18 diabetic foot ulcer patients: fat grafting; fat grafting with PRP; and routine podiatry care. Biopsies were obtained at week 0, 1, and 4, and underwent quantitative histology/immunohistochemistry (H&E, CD31, and Ki67). Treatment with fat and PRP increased mean microvessel density at 1 week to 1645 (SD 96) microvessels/mm2 (+32%-45% to other arms, P =.035). PRP appeared to increase vascularity surrounding fat grafts, and histology suggested PRP may enhance fat graft survival. There was no clinical difference between arms. This study demonstrates PRP with fat grafts increased neovascularisation and graft survival in diabetic foot ulcers. The histology was not, however, correlated with wound healing time. Future studies should consider using apoptosis markers and fluorescent labelling to ascertain if enhanced fat graft survival is due to proliferation or reduced apoptosis. Trial registration NCT03085550

Determining the outcomes of post-mastectomy radiation therapy delivered to the definitive implant in patients undergoing one- and two-stage implant-based breast reconstruction: A systematic review and meta-analysis

BACKGROUND: Post-mastectomy radiation therapy (PMRT) is known to increase the complication rate and implant loss in implant-based breast reconstruction. The purpose of this study was to systematically review the literature regarding the outcome of PMRT delivered to the permanent/definitive implant. METHODS: Systematic review and meta-analysis of studies involving immediate implant-based reconstruction and PMRT when delivered to the permanent implant. RESULTS: Seven studies included 2921 patients (520 PMRT, 2401 control). PMRT was associated with significant increase in capsular contracture (7 studies, 2529 patients, 494 PMRT, 2035 control, OR 10.21, 95% CI 3.74 to 27.89, p < 0.00001). In addition, PMRT was associated with a significant increase in revisional surgery (7 studies, 2921 patients, 520 PMRT, 2401 control, OR 2.18, 95% CI 1.33 to 3.57, p = 0.002) and reconstructive failure (6 studies, 2814 patients, 496 PMRT, 2318 control, OR 2.52, 95% CI 1.48 to 4.29, p+0.0007). Moreover, it was associated with a significant reduction in patient satisfaction (4 studies, 468 patients, 138 PMRT, 294 control, OR 0.29, 95% CI 0.15 to 0.57, p = 0.0003) and cosmetic outcome (4 studies, 1317 patients, 238 PMRT, 1009 control, OR 28, 95% CI. 0.11 to 0.67, p = 0.005). CONCLUSIONS: This meta-analysis demonstrates that within the first 5 years, post implant-based reconstruction for those patients who receive PMRT, the rates of adverse events are increased, and there is a significant reduction in patient satisfaction and cosmetic outcome