Paul S Cederna

Southern Illinois University Carbondale, Illinois, United States

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Publications (136)201.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with severe burns suffer functional, structural, and esthetic complications. It is important to explore reconstructive options given that no ideal treatment exists. Transfer of adipose and adipose-derived stem cells (ASCs) has been shown to improve healing in various models. The authors hypothesize that use of fat isografts and/or ASCs will improve healing in a mouse model of burn injury. Twenty 6 to 8 week old C57BL/6 male mice received a 30% surface area partial-thickness scald burn. Adipose tissue and ASCs from inguinal fat pads were harvested from a second group of C57BL/6 mice. Burned mice received 500 μ;l subcutaneous injection at burn site of 1) processed adipose, 2) ASCs, 3) mixed adipose (adipose and ASCs), or 4) sham (saline) injection (n = 5/group) on the first day postinjury. Mice were followed by serial photography until being killed at days 5 and 14. Wounds were assessed for burn depth and healing by hematoxylin and eosin (H&E) and immunohistochemistry. All treated groups showed improved healing over controls defined by decreased wound depth, area, and apoptotic activity. After 5 days, mice receiving ASCs or mixed adipose displayed a non-significant improvement in vascularization. No significant changes in proliferation were noted at 5 days. Adipose isografts improve some early markers of healing postburn injury. The authors demonstrate that addition of these grafts improves specific structural markers of healing. This improvement may be because of an increase in early wound vascularity postgraft. Further studies are needed to optimize use of fat or ASC grafts in acute and reconstructive surgery.
    Journal of burn care & research: official publication of the American Burn Association 09/2014; · 1.54 Impact Factor
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    ABSTRACT: The field of plastic surgery has been at the forefront of ideation and innovation. Surgeon scientists today continue to develop novel products that fulfill the needs of the medical community and patients. Part of this process requires the approval from various regulatory agencies and offices, including the U.S. Food and Drug Administration. Unfortunately, medical training does not include regulatory knowledge, and many surgeon scientists find the regulatory pathway and U.S. Food and Drug Administration perplexing, overly complicated, and insurmountable. The authors aim to clearly outline the path of the regulatory process as it pertains to the U.S. Food and Drug Administration and its various jurisdictions that may relate to the plastic surgeon.
    Plastic and reconstructive surgery. 09/2014; 134(3):559-569.
  • Jessica B Chang, Theodore A Kung, Paul S Cederna
    Annals of plastic surgery. 08/2014;
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    ABSTRACT: Heterotopic Ossification (HO) is a common, debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. While the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role. Interestingly, the prevalence of HO in the elderly population is low despite the high overall occurrence of musculoskeletal injury and orthopedic procedures. We hypothesized that a lower osteogenicity of MSCs would be associated with blunted HO formation in old compared to young mice. In vitro osteogenic differentiation of adipose-derived MSCs from old (18-20 months) and young (6-8 weeks) C57/BL6 mice was assessed, with or without preceding burn injury. In vivo studies were then performed using an Achilles tenotomy with concurrent burn injury HO model. HO formation was quantified using μCT scans, Raman spectroscopy, and histology. MSCs from young mice had more in vitro bone formation, up-regulation of bone formation pathways, and higher activation of Smad and NF-κB signaling following burn injury. This effect was absent or blunted in cells from old mice. In young mice, burn injury significantly increased HO formation, NF-κB activation, and osteoclast activity at the tenotomy site. This blunted, reactive osteogenic response in old mice follows trends seen clinically and may be related to differences in the ability to mount acute inflammatory responses. This unique characterization of heterotopic ossification and MSC osteogenic differentiation following inflammatory insult establishes differences between age populations and suggests potential pathways that could be targeted in the future with therapeutics.
    Stem cells and development. 08/2014;
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    ABSTRACT: Background Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer.Method We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer.ResultsPatients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40 % of patients treated with tendon transfers alone. Additionally, 57 % of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20 % in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength.Conclusion The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.
    Journal of Orthopaedic Surgery and Research 08/2014; 9(1):67. · 1.01 Impact Factor
  • Plastic and reconstructive surgery. 08/2014; 134(2):344e-6e.
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    ABSTRACT: High-fidelity volitional control of bioengineered prosthetic limbs with multiple degrees of freedom requires the implantation of multiple recording interfaces to detect independent control signals. However, interface utilization is complicated by interfering electrophysiological signals originating from surrounding muscles and nerves, leading to equivocal signal detection. We developed and validated a surgical model to characterize signal propagation through various biomaterials to identify insulating substrates for use in implantable interfaces. The identification of these insulating materials will facilitate the acquisition of noncontaminated prosthetic control signals, thus improving manipulation of advanced prosthetic limbs.
    Annals of plastic surgery. 07/2014;
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    ABSTRACT: The U.S. Food and Drug Administration is the government agency responsible for oversight of the safety and efficacy of pharmaceuticals and devices, including biologics and devices that combine biologics with other materials. Within the U.S. Food and Drug Administration, the Center for Biologics Evaluation and Research is specifically responsible for the evaluation and approval of biological products. This department of the U.S. Food and Drug Administration has a series of mechanisms in place to aid researchers in the process of developing new biologics. This article outlines the study phases involved in developing new biologics and how the Center for Biologics Evaluation and Research and investigators can work together to facilitate this process. It also discusses issues specific to biologics that have been encountered in the past and that investigators should consider when developing and obtaining approval for new biologics. The equivalent center within the U.S. Food and Drug Administration for approving medical devices is the Center for Devices and Radiological Health. The equivalent process of development and approval of medical devices is similarly discussed. Finally, essential contacts for investigators within the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health are provided.
    Plastic and reconstructive surgery. 06/2014; 133(6):1495-501.
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    ABSTRACT: The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer.
    Plastic and reconstructive surgery. 06/2014; 133(6):1380-94.
  • Plastic and reconstructive surgery 04/2014; 133(4 Suppl):1012-3. · 2.74 Impact Factor
  • Plastic and reconstructive surgery 04/2014; 133(4 Suppl):1015. · 2.74 Impact Factor
  • Jessica B Chang, Theodore A Kung, Paul S Cederna
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    ABSTRACT: Marjolin's ulcers are rare cutaneous malignancies that most commonly present as squamous cell carcinomas in previously injured, chronically inflamed, or scarred skin. Acute and chronic types have been distinguished by the length of latency; by definition, the acute type occurs within 12 months of injury whereas the chronic type appears over 12 months after injury. In this report, 3 cases of acute Marjolin's ulcers are described and questions are raised about the diagnosis of acute Marjolin's ulcer. Other than a discrepancy in lag time, it is unclear if there is any difference in clinical or histological characteristics or even prognosis between acute and chronic Marjolin's ulcers. In fact, the acute type may simply be a preemptive diagnosis that conveniently describes a carcinoma associated with a nonhealing wound and discovered within a short time span. Moreover, the rarity of the diagnosis and the relatively rapid rate of malignant degeneration from the inciting injury lead one to question whether the injury may have simply revealed or accelerated a previously existing occult cutaneous malignancy. With no definitive clinical, histological, or prognostic distinction between acute and chronic Marjolin's ulcers, the use of such terminology may not benefit a clinician's understanding or practice. In fact, it merely supports the clinical guideline that any nonhealing wound, acute or chronic, should be biopsied and sent for pathologic examination to ensure that it does not represent a Marjolin's ulcer.
    Annals of plastic surgery 03/2014; · 1.29 Impact Factor
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    ABSTRACT: The aim of this study was to demonstrate lymphatic isolation in a model of hind limb lymph node (LN) excision, consisting of ipsilateral popliteal and inguinal LN excision and to evaluate the immunologic response to allogeneic skin transplanted onto this region of lymphatic isolation. To study lymphatic flow, C57BL/6 mice underwent lymphadenectomy (n = 5), sham lymphadenectomy (n = 5), or no intervention (n = 5), followed by methylene blue injection. Mice were dissected to determine whether methylene blue traveled to the iliac LN. To study host response to skin transplantation, C57BL/6 mice underwent allogeneic skin transplantation with LN excision (n = 6), allogeneic skin transplantation alone (n = 6), or syngeneic skin transplantation (n = 4). Skin grafts were placed distal to the popliteal fossa and mice were euthanized at day 10. Grafts were stained for endothelial cell and proliferation markers (CD31 and Ki67, respectively). Secondary lymphoid tissues (spleen, ipsilateral axillary LN, and contralateral inguinal LN) were removed and rechallenged with BALB/c alloantigen in vitro with subsequent assay of interferon-γ and interleukin 4 cell expression using ELISPOT technique. Mice that underwent LN excision had no evidence of methylene blue in the iliac nodes; mice without surgical intervention or with sham LN excision consistently had methylene blue visible in the ipsilateral iliac nodes. Mice treated with allogeneic skin transplantation and LN excision had lower expression of interferon-γ and interleukin 4 in the secondary lymphoid tissues. Lymph node excision completely interrupts lymphatic flow of the hind limb. This model of lymphatic isolation impairs the ability of the transplant recipient to acutely mount a Th1 or Th2 response to allogeneic skin transplants.
    Annals of surgery 02/2014; · 7.90 Impact Factor
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    ABSTRACT: We describe the collaboration between an academic medical center and a free primary care clinic that provides multi-specialty services to indigent community members. Complementary components of both institutions have engendered a system in which they broaden the array of available services, providing a prototype for other institutions to consider.
    Journal of Health Care for the Poor and Underserved 01/2014; 25(3):1108-20. · 1.10 Impact Factor
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    ABSTRACT: Introduction. In adipose tissue healing, angiogenesis is stimulated by adipose-derived stromal stem cells (ASCs). Ventral hernia repair (VHR) patients are at high risk for wound infections. We hypothesize that ASCs from VHR patients are less vasculogenic than ASCs from healthy controls. Methods. ASCs were harvested from the subcutaneous fat of patients undergoing VHR by the component separation technique and from matched abdominoplasty patients. RNA and protein were harvested on culture days 0 and 3. Both groups of ASCs were subjected to hypoxic conditions for 12 and 24 hours. RNA was analyzed using qRT-PCR, and protein was used for western blotting. ASCs were also grown in Matrigel under hypoxic conditions and assayed for tubule formation after 24 hours. Results. Hernia patient ASCs demonstrated decreased levels of VEGF-A protein and vasculogenic RNA at 3 days of growth in differentiation media. There were also decreases in VEGF-A protein and vasculogenic RNA after growth in hypoxic conditions compared to control ASCs. After 24 hours in hypoxia, VHR ASCs formed fewer tubules in Matrigel than in control patient ASCs. Conclusion. ASCs derived from VHR patients appear to express fewer vasculogenic markers and form fewer tubules in Matrigel than ASCs from abdominoplasty patients, suggesting decreased vasculogenic activity.
    BioMed research international. 01/2014; 2014:983715.
  • Plastic and Reconstructive Surgery. 01/2014; 133(3s):10-99.
  • Plastic and Reconstructive Surgery. 01/2014; 133(3s):200.
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    ABSTRACT: Advancements in modern robotic technology have led to the development of highly sophisticated upper extremity prosthetic limbs. High-fidelity volitional control of these devices is dependent on the critical interface between the patient and the mechanical prosthesis. Recent innovations in prosthetic interfaces have focused on several control strategies. Targeted muscle reinnervation is currently the most immediately applicable prosthetic control strategy and is particularly indicated in proximal upper extremity amputations. Investigation into various brain interfaces has allowed acquisition of neuroelectric signals directly or indirectly from the central nervous system for prosthetic control. Peripheral nerve interfaces permit signal transduction from both motor and sensory nerves with a higher degree of selectivity. This article reviews the current developments in each of these interface systems and discusses the potential of these approaches to facilitate motor control and sensory feedback in upper extremity neuroprosthetic devices.
    Plastic and reconstructive surgery 12/2013; 132(6):1515-23. · 2.74 Impact Factor
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    ABSTRACT: Little knowledge exists concerning replantation following traumatic major upper extremity amputation. This study characterizes the injury patterns and outcomes of patients suffering major upper extremity amputation and ascertains clinical factors associated with the decision to attempt replantation. A retrospective cohort study was conducted on patients treated at a Level I trauma center between June of 2000 and August of 2011. Patients who experienced traumatic upper extremity amputation at or proximal to the radiocarpal joint were included in the study. The subset of patients subsequently undergoing replantation was identified. Medical records were reviewed and bivariate analysis was performed to identify factors associated with attempted replantation and replant survival. Sixty-two patients were treated for traumatic upper extremity amputation and 20 patients underwent replantation. Injury factors associated with attempted replantation included a sharp/penetrating injury (p = 0.004), distal level of amputation (p = 0.017), Injury Severity Score less than 16 (p = 0.020), absence of avulsion (p = 0.002), absence of significant contamination (p ≤ 0.001), and lack of multilevel involvement (p = 0.007). Replantation exhibited a complete replant survival rate of 70 percent. An Injury Severity Score of 16 or more was associated with replant failure (p = 0.004). Patients who underwent replantation demonstrated increased rates of secondary surgical revisions (p ≤ 0.001) and complications (p = 0.023) and had a greater length of hospital stay (p = 0.024). Several injury characteristics are associated with the decision to attempt replantation of the major upper extremity. A high global injury severity (Injury Severity Score ≥ 16) is associated with replantation failure when attempted. Patients who undergo replantation demonstrate higher resource use, warranting further cost-analysis and outcomes investigation. Risk, III.
    Plastic and reconstructive surgery 10/2013; 132(4):911-9. · 2.74 Impact Factor
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    ABSTRACT: Sarcopenia leads to many changes in skeletal muscle that contribute to atrophy, force deficits, and subsequent frailty. The purpose of this study was to characterize motor unit remodeling related to sarcopenia seen in extreme old age. Whole extensor digitorum longus muscle and motor unit contractile properties were measured in 19 adult (11-13 months) and 12 oldest old (36-37 months) Brown-Norway rats. Compared with adults, oldest old rats had significantly fewer motor units per muscle, smaller muscle cross-sectional area, and lower muscle specific force. However, mean motor unit force generation was similar between the two groups due to an increase in innervation ratio by the oldest old rats. These findings suggest that even in extreme old age both fast- and slow-twitch motor units maintain the ability to undergo motor unit remodeling that offsets some effects of sarcopenia.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2013; · 4.31 Impact Factor

Publication Stats

887 Citations
201.26 Total Impact Points

Institutions

  • 2013
    • Southern Illinois University Carbondale
      Illinois, United States
    • Michigan State University
      East Lansing, Michigan, United States
  • 1999–2013
    • University of Michigan
      • • Department of Surgery
      • • Section of Plastic and Reconstructive Surgery
      • • Department of Obstetrics and Gynecology
      • • Department of Biomedical Engineering
      Ann Arbor, MI, United States
  • 2012
    • Pennsylvania State University
      • Department of Bioengineering
      University Park, MD, United States
  • 2000–2011
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2005–2007
    • Washington University in St. Louis
      • Division of Plastic Surgery
      Saint Louis, MO, United States
  • 2004
    • Duke University
      Durham, North Carolina, United States
  • 1999–2002
    • The University of Tokyo
      • Department of Plastic, Reconstructive and Aesthetic Surgery
      Tokyo, Tokyo-to, Japan
  • 2001
    • Duke University Medical Center
      Durham, North Carolina, United States