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

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

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

Protocol for a systematic review of the efficacy of epidermal grafting for wound healing

BACKGROUND: Autologous skin grafting is an important modality for wound coverage; however, it can result in donor site morbidity. Epidermal grafting is an emerging option to overcome this challenge. Furthermore, it can be done in an outpatient setting with minimal or no pain. To date, the evidence on the efficacy of this technique for wound healing has yet to be outlined. We aim to synthesise the current evidence on epidermal grafting for wound healing to establish the efficacy of this technique. METHODS/DESIGN: We will conduct a comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases (up to May 2016) to identify studies on epidermal grafting for wound healing. We will include any primary studies (excluding case reports or case series lesser than three patients) or systematic reviews of such studies to assess the outcome of epidermal grafting for wound healing either on its own or compared to other methods. The expected primary outcome measures are the efficacy of epidermal grafting for wound healing (measured by the proportion of wounds healed at 6 weeks) and the mean wound-healing time (time for complete re-epithelialisation). Secondary outcome measures are the mean donor site-healing time, need for anaesthesia, costs associated with resource use, health-related quality of life, and proportion of patients with adverse event. Subgroup analysis will be performed for the proportions of wounds healed based on wound aetiology. DISCUSSION: This is a timely systematic review, and the finding of this systematic review is expected to guide research and clinical practice aimed at improving wound care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033051

A Facile Method for Generating Worm-like Micelles with Controlled Lengths and Narrow Polydispersity

This work shows that highly uniform worm micelles formed by polymerisation induced self-assembly can be obtained via simple postsynthesis sonication. Importantly, this straightforward and versatile strategy yields exceptionally monodisperse worms with tunable aspect ratios ranging from 7.2 to 17.6 by simply changing the sonication time

The CelluTome epidermal graft-harvesting system: a patient-reported outcome measure and cost evaluation study

Conventional split skin grafts (SSG) require anaesthesia, specialist equipment and can have high donor site (DS) morbidity. The CelluTome epidermal graft-harvesting device is a novel alternative, providing pain-free epidermal skin grafts (ESG) in the outpatient setting, with projected minimal DS trauma and improved patient satisfaction. This study aimed to compare ESG with SSG by evaluating patient-related outcome measures (PROMs) and the cost implications of both. Twenty patients answered a graft satisfaction questionnaire that evaluated: donor/graft site noticeability, aesthetic concerns, adverse problems and patient satisfaction. Cost/patient was calculated based on total operative expenses and five clinic follow-ups. In 100% of the ESG cases, there were no DS noticeability or adverse problems compared to 25% in the SSG group. Complete satisfaction with DS appearance was observed in 100% of the ESG cases (50% SSG). Noticeability, adverse problems and overall satisfaction were significantly better in ESG cases (P < 0.05). Graft site parameters were comparable with similar healing outcomes. The cost per patient for ESG was £431 and £1489 for SSG, with an annual saving of £126 960 based on 10 grafts/month. For the right patient, CelluTome provides comparable wound healing, with reduced DS morbidity and higher patient satisfaction

Protocol for a systematic review of the efficacy of fat grafting and platelet-rich plasma for wound healing

BACKGROUND: The use of fat grafting as a reconstructive surgical option is becoming much more common. Adipose-derived stem cells found in fat grafts are believed to facilitate wound healing via differentiation into fibroblasts and keratinocytes and the release of pro-healing growth factors. Several small studies have shown a positive effect of fat grafting in healing of wounds of a variety of aetiologies. When fat is combined with autologous platelet-rich plasma (PRP), there may be enhanced healing effects. This may be due to the pro-angiogenic and anti-inflammatory effects of PRP. We aim to synthesise the current evidence on combination fat grafting and PRP for wound healing to establish the efficacy of this technique. METHODS/DESIGN: We will conduct a comprehensive literature search in the MEDLINE, EMBASE, CENTRAL, Science Citation Index, and Google Scholar databases (up to July 2017) to identify studies on fat grafting and PRP for wound healing. All primary studies and systematic reviews of these studies will be included, except case reports and case series with fewer than three patients, to evaluate the outcome of fat grafting and PRP on wound healing either on its own or when compared to other studies. Primary outcome measures are expected to be the proportion of total wounds healed at 12 weeks and the average wound healing time (time for 100% re-epithelialisation). Expected secondary outcome measures are the proportion of wounds achieving 50% wound healing, the type of wound benefitting most from fat grafting, economic evaluation, health-related quality of life, and adverse events. Subgroup analysis will be performed for the proportions of wounds healed based on wound aetiology. DISCUSSION: This review will provide robust evidence of the efficacy of fat grafting and PRP for wound healing. This is an emerging technique, and this review is expected to guide clinical practice and ongoing research aimed at improving wound care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049881

Systematic review of the efficacy of fat grafting and platelet-rich plasma for wound healing

Adipose‐derived stem cells found in fat grafts may have significant healing properties. When fat is combined with autologous platelet‐rich plasma (PRP), there may be enhanced healing effects due to the pro‐angiogenic and anti‐inflammatory effects of PRP. This study aimed to evaluate the current evidence on fat grafting in combination with PRP for wound healing to establish the efficacy of this technique. A comprehensive search in the MEDLINE, EMBASE, CENTRAL, Science Citation Index, and Google Scholar databases (to March 2017) was conducted to identify studies on fat grafting and PRP for wound healing. Case series of less than 3 cases and studies only describing harvest technique were excluded. The database identified 571 articles, of which 3 articles that used a combination of fat and PRP for wound healing (1 RCT and 2 case series) were included in this review. A total of 69 wounds in 64 patients were treated with an average wound size of 36.32cm2. Of these, 67% of wounds achieved complete healing. When reported, the mean time to healing was 7.5 weeks for those who underwent a single treatment. There were no significant complications in any patients. The combination of fat grafting and PRP may achieve adequate wound healing with relatively quick wound healing time compared with standard wound management options. However, evidence is extremely limited, and further studies are required to evaluate its efficacy for wound healing