Nicolò Bertozzi

The biological and clinical basis for the use of adipose-derived stem cells in the field of wound healing

Worldwide, hard-to-heal lower limb wounds are estimated to affect 1.5–3% of the adult population with a treatment-related annual cost of

Procedure, applications, and outcomes of autologous fat grafting

10 billion. Thus, chronic skin ulcers of the lower limb are a matter of economic and public concern. Over the years, multiple medical and surgical approaches have been proposed but they are still inadequate, and no effective therapy yet exists. Regenerative medicine and stem cell-based therapies hold great promise for wound healing. Recently, many plastic surgeons have studied the potential clinical application of adipose-derived stem cells (ASCs), which are a readily available adult stem cell population that can undergo multilineage differentiation and secrete growth factors that can enhance wound-healing processes by promoting angiogenesis, and hence increase local blood supply. ASCs have been widely studied in vitro and in vivo in animal models. However, there are few randomized clinical trials on humans, and these are still ongoing or recruiting patients. Moreover, there is no consensus on a common isolation protocol that is clinically feasible and which would ensure reproducible results. The authors aim to provide readers with an overview of the biological properties of ASCs as well as their clinical application, to help better understanding of present and future strategies for the treatment of hard-to-heal wounds by means of stem cell-based therapies.

Autologous fat transplantation for breast reconstruction: A literature review

Objective To systematically review the procedure, applications, and outcomes of autologous fat grafting, a promising technique with various clinical applications. Patients and methods Literature review of publications concerning autologous fat grafting. Results Since its introduction, lipofilling has become increasingly popular; however, its results are variable and unpredictable. Several modifications have been made to the procedures of fat harvesting, processing, and injecting. Surgical excision and low negative-pressure aspiration with large-bore cannulas minimize adipocyte damage during fat harvesting. The “wet” method of fat harvesting involves fluid injection at the donor site and facilitates lipoaspiration while minimizing pain and ecchymosis. For fat processing, centrifugation at a low speed is preferable to high-speed centrifugation, gravity separation or filtration. Fat injection at the recipient site should be performed using small-gauge cannulas in a fanning out pattern over multiple sessions, rather than a single session. Fat grafts exhibit not only dermal filler properties but also regenerative potential owing to the presence of stem cells in fat tissue. Thus, the clinical applications of autologous fat grafting include correction of secondary contour defects after breast reconstruction, release of painful scar contractures, and treatment of burn scars and radiodermatitis. Lipofilling is also used in aesthetic surgery, such as facial and hand rejuvenation, augmentation rhinoplasty, and breast and gluteal augmentation. The complications of lipofilling are minimal and include bruising, swelling, pain, infection, necrosis, and calcification. Conclusions Lipofilling is a low-risk procedure that can be used to correct soft-tissue defects in the face, trunk, and extremities, with minimal discomfort for patients.

Isolation of Ready‐to‐Use Adipose‐Derived Stem Cell (ASC) Pellet for Clinical Applications and a Comparative Overview of Alternate Methods for ASC Isolation

Introduction The use of autologous fat transplantation to correct volume and contour defects, scars, and asymmetry after breast cancer surgery has increased over the past 20 years. Many developments and refinements in this technique have taken place in recent years, and several studies of the safety of lipofilling in the breast have been published. Presentation of case We performed a literature review of this technique, highlighting the crucial role of lipofilling in breast cancer reconstruction. Discussion The efficacy of the fat graft transplantation depends on the experience and the technique used by the surgeon. The ASCs (adipose-derived stem cells) contained in the fat graft has proven to be crucial for breast reconstruction by mean the regeneration of tissue, through the chemotactic, paracrine, and immunomodulatory activities and their in situ differentiation. Conclusion The role of lipofilling for breast reconstruction could be more significant with the application of the findings of experimental research on tissue engineering and ASCs.

Breast reconstruction with anatomical implants: A review of indications and techniques based on current literature

Current literature does not offer a standardized method to isolate adipose-derived stem cells (ASCs) for clinical applications and hence clinical studies using ASCs often show inconsistent results. Most of these studies borrow laboratory or benchside-derived protocols, which are complex, time consuming, and involve the use of chemical, animal-derived reagents. In this unit we describe a relatively simple and faster isolation protocol that allows collection of a ready-to-use ASC pellet for clinical application. All steps are performed in a closed circuit in order to guarantee maximum process sterility. Once the adipose tissue is harvested by means of a standard liposuction procedure, it undergoes a first centrifugation in order to remove the oil and serous fractions. Then ASCs are released by enzymatic digestion from the surrounding connective tissue scaffold. Finally a double series of washing and centrifugation allows one to obtain the ASC pellet alone. We usually graft this ASC pellet onto the skin edge and to the bottom of chronic skin ulcers as ASCs proved to be effective in promoting wound healing processes. Moreover, an increasing number of clinical studies are currently ongoing to test their potential in every medical field, from orthopedics to cardiology, oncology, autoimmune diseases, and tissue engineering.

Tissue expansion for breast reconstruction: Methods and techniques

One important modality of breast cancer therapy is surgical treatment, which has become increasingly less mutilating over the last century. Breast reconstruction has become an integrated part of breast cancer treatment due to long-term psychosexual health factors and its importance for breast cancer survivors. Both autogenous tissue-based and implant-based reconstruction provides satisfactory reconstructive options due to better surgeon awareness of “the ideal breast size”, although each has its own advantages and disadvantages. An overview of the current options in breast reconstruction is presented in this article.

Off-label use of adipose-derived stem cells

Objective In this work, the authors review recent data on the different methods and techniques of TE/implant-based reconstruction to determine the complication profiles and the advantages and disadvantages of the different techniques. This information will be valuable for surgeons performing breast reconstructions. Materials and methods A thorough literature review was conducted by the authors concerning the current strategy of tissue expander (TE)/implant-based breast reconstruction following breast cancer surgery. Results Loss of the breast can strongly affect a womans personal and social life while breast reconstruction reduces the sense of mutilation felt by women after a mastectomy, and provides psychosocial as well as aesthetic benefits. TE/implant-based reconstruction is the most common breast reconstructive strategy, constituting almost 65% of all breast reconstructions in the US. Although numerous studies have been published on various aspects of alloplastic breast reconstructions, most studies are single-center observations. No evidence-based guidelines are available as yet. Conventional TE/implant-based reconstruction can be performed as a two-stage procedure either in the immediate or delayed setting. Moreover, the adjunctive use of acellular dermal matrix further broadened the alloplastic breast reconstruction indication and also enhanced aesthetic outcomes. Conclusions TE/implant-based reconstruction has proved to be a safe, cost-effective, and reliable technique that can be performed in women with various comorbidities. Short operative time, fast recovery, and absence of donor site morbidity are other advantages over autologous breast reconstruction.

One-Stage Immediate Breast Reconstruction: A Concise Review

Background Adipose-derived stem cells (ASCs) have a broad range of clinical applications. The ease of cell harvest and high yield with minimal donor-site morbidity makes adipose tissue an ideal source of stem cells. Further, the multi-lineage potential of these cells present significant opportunities within the field of tissue engineering, with studies successfully demonstrating their ability to produce a range of tissue types. Materials and methods Literature review of publications on the use of ASCs, in the context of current European and US regulations. Results According to European and US regulations, many clinical trials reported in literature to date could be considered off-label. Conclusion In Europe, clinical trials involving cultured ASCs and/or the use of collagenase, which causes changes in the structural and functional properties of stem cells, and/or ASCs application in non-homologous tissue, should be considered off-label. ASCs should be non-cultured, isolated mechanically, and used only in the subcutaneous tissue.

Ultrastructural effects of topical dimethyl sulfoxide on collage fibers during acute skin expansion in a human ex-vivo model

Background One-stage direct-to-implant immediate breast reconstruction (IBR) is performed simultaneously with breast cancer resection. We explored indications, techniques, and outcomes of IBR to determine its feasibility, safety, and effectiveness. Material and Methods We reviewed the available literature on one-stage direct-to-implant IBR, with or without acellular dermal matrix (ADM), synthetic mesh, or autologous fat grafting. We analyzed the indications, preoperative work-up, surgical technique, postoperative care, outcomes, and complications. Results IBR is indicated for small-to-medium nonptotic breasts and contraindicated in patients who require or have undergone radiotherapy, due to unacceptably high complications rates. Only patients with thick, well-vascularized mastectomy flaps are IBR candidates. Expandable implants should be used for ptotic breasts, while anatomical shaped implants should be used to reconstruct small-to-medium nonptotic breasts. ADMs can be used to cover the implant during IBR and avoid muscle elevation, thereby minimizing postoperative pain. Flap necrosis, reoperation, and implant loss are more common with IBR than conventional two-staged reconstruction, but IBR has advantages such as lack of secondary surgery, faster recovery, and better quality of life. Conclusions IBR has good outcomes and patient-satisfaction rates. With ADM use, a shift from conventional reconstruction to IBR has occurred. Drawbacks of IBR can be overcome by careful patient selection.

The Art and Science beyond Body Contouring A Solution for Massive Weight Loss Patients

BackgroundDespite some studies confirming the effectiveness of dimethyl sulfoxide (DMSO) on acute skin expansion, the precise mechanism through which it quickens tissue expansion is yet unknown. No studies have been carried out to date to thoroughly investigate the ultrastructural effects of DMSO on intraoperative tissue expansion. The aim of the present study was to test the ex vivo ultrastructural effects of topical 60% DMSO on dermal collagen fibers of acutely expanded human cutaneous flaps.MethodsSpecimens were obtained and ultrastructurally examined from two groups of ex vivo cutaneous flaps from the anterior thigh: group A (experimental) DMSO-treated and acutely expanded flaps, and group B (control), acutely expanded flaps.ResultsA statistically significant difference was observed between groups A and B, with respect to the width of dermal collagen fibers, distance between dermal collagen fibers, and percentage of area not occupied by collagen fibers.ConclusionsThese findings demonstrate how DMSO affects collagen cross-linkage in the surrounding dermis, decreasing the mechanical resistance of the acutely expanded skin in this ex-vivo model, supporting its use in intra-operative tissue expansion.Level of Evidence: Not ratable.