Ara A. Salibian

Stem Cells in Plastic Surgery: A Review of Current Clinical and Translational Applications

Background Stem cells are a unique cell population characterized by self-renewal and cellular differentiation capabilities. These characteristics, among other traits, make them an attractive option for regenerative treatments of tissues defects and for aesthetic procedures in plastic surgery. As research regarding the isolation, culture and behavior of stem cells has progressed, stem cells, particularly adult stem cells, have shown promising results in both translational and clinical applications. Methods The purpose of this review is to evaluate the applications of stem cells in the plastic surgery literature, with particular focus on the advances and limitations of current stem cell therapies. Different key areas amenable to stem cell therapy are addressed in the literature review; these include regeneration of soft tissue, bone, cartilage, and peripheral nerves, as well as wound healing and skin aging. Results The reviewed studies demonstrate promising results, with favorable outcomes and minimal complications in the cited cases. In particular, adipose tissue derived stem cell (ADSC) transplants appear to provide effective treatment options for bony and soft tissue defects, and non-healing wounds. ADSCs have also been shown to be useful in aesthetic surgery. Conclusions Further studies involving both the basic and clinical science aspects of stem cell therapies are warranted. In particular, the mechanism of action of stem cells, their interactions with the surrounding microenvironment and their long-term fate require further elucidation. Larger randomized trials are also necessary to demonstrate the continued safety of transplanted stem cells as well as the efficacy of cellular therapies in comparison to the current standards of care.

Implications for human adipose‐derived stem cells in plastic surgery

Adipose‐derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) that possess many of the same regenerative properties as other MSCs. However, the ubiquitous presence of ADSCs and their ease of access in human tissue have led to a burgeoning field of research. The plastic surgeon is uniquely positioned to harness this technology because of the relative frequency in which they perform procedures such as liposuction and autologous fat grafting. This review examines the current landscape of ADSC isolation and identification, summarizes the current applications of ADSCs in the field of plastic surgery, discusses the risks associated with their use, current barriers to universal clinical translatability, and surveys the latest research which may help to overcome these obstacles.

Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration.

Peripheral nerve injury requiring nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for nerve regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional nerve grafting procedures. This review presents a different approach to nerve regeneration. The literature was reviewed to evaluate current methods of using adipose‐derived stem cells (ADSCs) for peripheral nerve regeneration in in vivo models of animal peripheral nerve injury. The authors present cited evidence for directing nerve regeneration through paracrine effects of ADSCs rather than through in vitro nerve regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo nerve regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory nerve regeneration have been forthcoming. The ADSCs are initially “primed” in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen‐based nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed.

Early Intervention to Promote Medical Student Interest in Surgery and the Surgical Subspecialties

OBJECTIVE Concerns about projected workforce shortages are growing, and attrition rates among surgical residents remain high. Early exposure of medical students to the surgical profession may promote interest in surgery and allow students more time to make informed career decisions. The objective of this study was to evaluate the impact of a simple, easily reproducible intervention aimed at increasing first- and second-year medical student interest in surgery. DESIGN Surgery Saturday (SS) is a student-organized half-day intervention of four faculty-led workshops that introduce suturing, knot tying, open instrument identification, operating room etiquette, and basic laparoscopic skills. Medical students who attended SS were administered pre-/post-surveys that gauged change in surgical interest levels and provided a self-assessment (1-5 Likert-type items) of knowledge and skills acquisition. PARTICIPANTS First- and second-year medical students. OUTCOME MEASURES Change in interest in the surgical field as well as perceived knowledge and skills acquisition. RESULTS Thirty-three first- and second-year medical students attended SS and completed pre-/post-surveys. Before SS, 14 (42%) students planned to pursue a surgical residency, 4 (12%) did not plan to pursue a surgical residency, and 15 (46%) were undecided. At the conclusion, 29 (88%) students indicated an increased interested in surgery, including 87% (13/15) who were initially undecided. Additionally, attendees reported a significantly (p < 0.05) higher comfort level in the following: suturing, knot tying, open instrument identification, operating room etiquette, and laparoscopic instrument identification and manipulation. CONCLUSIONS SS is a low resource, high impact half-day intervention that can significantly promote early medical student interest in surgery. As it is easily replicable, adoption by other medical schools is encouraged.

“Strategic sequences” in adipose-derived stem cell nerve regeneration

Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques using human adipose‐derived stem cells (hADSCs) for nerve regeneration and derive a comprehensive approach to hADSC therapy for PNI.

Orbital Floor Fractures: A Retrospective Review of 45 Cases at a Tertiary Health Care Center

The purpose of this retrospective study was to investigate treatment options for orbital floor fractures at a Level 1 Trauma Center in Southern California. A review of 45 cases of isolated orbital floor fractures treated at the University of California at Irvine between February 2004 and April 2007 was done. Patients were retrospectively analyzed for gender, age, mechanism of injury, associated facial injuries, presenting symptoms, method of treatment, and postoperative complications. Thirty-six male patients and nine female patients were treated. Motor vehicle collision (26/45) was the most common cause of injury, and the mean age of the patients was 35.5 years (range: 15—81 years). Ecchymosis surrounding the orbital tissue was the most common presentation (38/45). Diplopia was present in 8 of 45 patients, with 1 patient requiring urgent decompression for retrobulbar hematoma. Forty-three patients underwent surgical repair; 40 underwent transconjunctival approach with lateral canthotomy; 17 underwent reconstruction with porous polyethylene Medpor (Porex Surgical, Inc., College Park, GA.); and 26 underwent reconstruction with a titanium mesh plate. Immediate postoperative complications included 12 patients with infraorbital numbness, 3 with diplopia, 1 with cellulitis, and 1 with ectropion with a subcilliary approach. Average timing of surgery of our study was 4.94 days (range, 1—20 days). Orbital floor fracture management has changed significantly over the past few decades with the introduction of new internal fixation methods and new materials for reconstructing orbital floor defects. Recommendations for surgical intervention on orbital floor fractures mostly depend on clinical examination and imaging studies. Consequences of inadequate repair of orbital floor fractures can lead to significant facial asymmetry and visual problems. Both porous polyethylene and titanium plates are effective tools for reconstructing the orbital floor. Our review demonstrates that orbital floor fractures can be repaired safely with minimal postoperative complications and confirms that transconjunctival approach to orbital floor is an effective way for exposure and prevention of ectropion that can be seen with other techniques.

Capsular Contracture in Implant-Based Breast Reconstruction: Examining the Role of Acellular Dermal Matrix Fenestrations.

Background: Acellular dermal matrices have been proposed to decrease the incidence of capsular contracture in implant-based breast reconstructions. The authors have modified acellular dermal matrices with fenestrations to facilitate greater lower pole expansion and improve contour. The effect of fenestrations on the ability of matrices to suppress capsule formation, however, has not been examined. Methods: A retrospective review of all fenestrated acellular dermal matrix–assisted, implant-based breast reconstructions performed by the two senior authors, with a minimum of 1-year follow-up after permanent implant placement, was completed. Patient demographics, details of extirpative and reconstructive procedures, and complications were examined. Capsular contractures were scored according to the Baker grading scale and compared to those reported in the literature. Results: Thirty patients (50 breasts) underwent fenestrated acellular dermal matrix–assisted reconstruction, with mean follow-up times of 3.3 and 2.6 years after expander placement and implant exchange, respectively. Seven patients (23 percent) had a body mass index greater than 30 kg/m2, three (10 percent) were active smokers, and six breasts (12 percent) were irradiated. Complications included one infection (2 percent), six cases (12 percent) of incisional superficial skin necrosis, and one (2 percent) tissue expander extrusion. Zero breasts had clinically significant Baker grade III/IV capsular contracture. The average Baker grade was 1.1. Conclusions: Fenestrated acellular dermal matrices decrease capsular contracture to rates similar to what is seen with nonfenestrated matrices. Further research is necessary to determine whether this observation is a result of decreased need for inferolateral acellular dermal matrix coverage to achieve these effects or modified physical interaction of acellular dermal matrices with surrounding soft tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Subcutaneous Implant-based Breast Reconstruction with Acellular Dermal Matrix/Mesh: A Systematic Review

Background: The availability of acellular dermal matrix (ADM) and synthetic mesh products has prompted plastic surgeons to revisit subcutaneous implant-based breast reconstruction. The literature is limited, however, with regards to evidence on patient selection, techniques, and outcomes. Methods: A systematic review of the Medline and Cochrane databases was performed for original studies reporting breast reconstruction with ADM or mesh, and subcutaneous implant placement. Studies were analyzed for level of evidence, inclusion/exclusion criteria for subcutaneous reconstruction, reconstruction characteristics, and outcomes. Results: Six studies (186 reconstructions) were identified for review. The majority of studies (66.7%) were level IV evidence case series. Eighty percent of studies had contraindications for subcutaneous reconstruction, most commonly preoperative radiation, high body mass index, and active smoking. Forty percent of studies commenting on patient selection assessed mastectomy flap perfusion for subcutaneous reconstruction. Forty-five percent of reconstructions were direct-to-implant, 33.3% 2-stage, and 21.5% single-stage adjustable implant, with ADM utilized in 60.2% of reconstructions versus mesh. Pooled complication rates included: major infection 1.2%, seroma 2.9%, hematoma 2.3%, full nipple-areola complex necrosis 1.1%, partial nipple-areola complex necrosis 4.5%, major flap necrosis 1.8%, wound healing complication 2.3%, explantation 4.1%, and grade III/IV capsular contracture 1.2%. Conclusions: Pooled short-term complication rates in subcutaneous alloplastic breast reconstruction with ADM or mesh are low in preliminary studies with selective patient populations, though techniques and outcomes are variable across studies. Larger comparative studies and better-defined selection criteria and outcomes reporting are needed to develop appropriate indications for performing subcutaneous implant-based reconstruction.

Current concepts on burn wound conversion-A review of recent advances in understanding the secondary progressions of burns.

Burn wound conversion describes the process by which superficial partial thickness burns convert into deeper burns necessitating surgical intervention. Fully understanding and thus controlling this phenomenon continues to defy burn surgeons. However, potentially guiding burn wound progression so as to obviate the need for surgery while still bringing about healing with limited scarring is the major unmet challenge. Comprehending the pathophysiologic background contributing to deeper progression of these burns is an essential prerequisite to planning any intervention. In this study, a review of articles examining burn wound progression over the last five years was conducted to analyze trends in recent burn progression research, determine changes in understanding of the pathogenesis of burn conversion, and subsequently examine the direction for future research in developing therapies. The majority of recent research focuses on applying therapies from other disease processes to common underlying pathogenic mechanisms in burn conversion. While ischemia, inflammation, and free oxygen radicals continue to demonstrate a critical role in secondary necrosis, novel mechanisms such as autophagy have also been shown to contribute affect significantly burn progression significantly. Further research will have to determine whether multiple mechanisms should be targeted when developing clinical therapies.

Single-Lumen and Multi-Lumen Poly(Ethylene Glycol) Nerve Conduits Fabricated by Stereolithography for Peripheral Nerve Regeneration In Vivo

BACKGROUND The use of nerve conduits to facilitate nerve regrowth after peripheral nerve injury is limited to defects less than 3 cm. The purpose of this study is to determine the capability of novel single and multi-lumen poly(ethylene glycol) (PEG) conduits manufactured by stereolithography to promote peripheral nerve regeneration. MATERIALS AND METHODS Eight Sprague Dawley rats with sharp transection injuries of the sciatic nerve were randomly assigned to receive single-lumen or multi-lumen PEG conduits to bridge a 10-mm gap. Sciatic nerve and conduit samples were harvested after 5 weeks, and axon number, myelin thickness, fiber diameter, and g-ratio were analyzed. The contralateral intact nerve was also harvested for comparison. RESULTS Partial nerve regeneration was observed in three out of four single-lumen conduits and one out of four multi-lumen conduits. Axon number in the single-lumen regenerated nerve approached that of the contralateral intact nerve at 4,492 ± 2,810.0 and 6,080 ± 627.9 fibers/mm(2), respectively. The percentage of small fibers was greater in the single-lumen conduit compared with the intact nerve, whereas myelin thickness and g-ratio were consistently greater in the autologous nerve. Axon regrowth through the multi-lumen conduits was severely limited. CONCLUSION Single-lumen stereolithography-manufactured PEG nerve conduits promote nerve regeneration, with regenerating axon numbers approaching that of normal nerve. Multi-lumen conduits demonstrated significantly less nerve regeneration, possibly due to physical properties of the conduit inhibiting growth. Further studies are necessary to compare the efficacy of the two conduits for functional recovery and to elucidate the reasons underlying their differences in nerve regeneration potential.