Bohdan Pomahac

Dermatan Sulfate Released after Injury Is a Potent Promoter of Fibroblast Growth Factor-2 Function

Proteoglycans have been shown in vitro to bind multiple components of the cellular microenvironment that function during wound healing. To study the composition and function of these molecules when derived from anin vivo source, soluble proteoglycans released into human wound fluid were characterized and evaluated for influence on fibroblast growth factor-2 activity. Immunoblot analysis of wound fluid revealed the presence of syndecan-1, syndecan-4, glypican, decorin, perlecan, and versican. Sulfated glycosaminoglycan concentrations ranged from 15 to 65 μg/ml, and treatment with chondroitinase B showed that a large proportion of the glycosaminoglycan was dermatan sulfate. The total glycosaminoglycan mixture present in wound fluid supported the ability of fibroblast growth factor-2 to signal cell proliferation. Dermatan sulfate, and not heparan sulfate, was the major contributor to this activity, and dermatan sulfate bound FGF-2 withK d = 2.48 μm. These data demonstrate that proteoglycans released during wound repair are functionally active and provide the first evidence that dermatan sulfate is a potent mediator of fibroblast growth factor-2 responsiveness.

Three Patients with Full Facial Transplantation

Unlike conventional reconstruction, facial transplantation seeks to correct severe deformities in a single operation. We report on three patients who received full-face transplants at our institution in 2011 in operations that aimed for functional restoration by coaptation of all main available motor and sensory nerves. We enumerate the technical challenges and postoperative complications and their management, including single episodes of acute rejection in two patients. At 6 months of follow-up, all facial allografts were surviving, facial appearance and function were improved, and glucocorticoids were successfully withdrawn in all patients.

Accelerated healing of full-thickness skin wounds in a wet environment.

Full-thickness skin wounds are preferably allowed to heal under controlled hydration dressings such as hydrocolloids. It was hypothesized that a wet (liquid) environment rather than a dry or moist one would accelerate the wound healing process. We compared skin repair by secondary intention in full-thickness skin wounds in wet (saline), moist (hydrocolloid), and dry (gauze) conditions in an established porcine wound healing model. The study included three animals with a total of 70 wounds layered in a standardized fashion on the back of young Yorkshire pigs. Twelve days after wounding, 0 percent of dry, 20 percent of moist, and 86 percent of saline-treated wounds were completely reepithelialized (p values = 0.0046 and 0.027 for saline wounds compared with dry and moist wounds, respectively). The accelerated healing was caused at least in part by faster contraction in wet wounds (p value < 0.005 compared with that of other groups 9 and 12 days after wounding). Development of granulation tissue was faster in moist conditions than it was for dry and wet wounds. The thickness and number of cell layers of the newly formed epidermis were greater in dry and wet wounds than in moist ones. It was concluded that these full-thickness porcine skin wounds healed faster in a wet environment than in a moist one. Dry wounds healed more slowly than moist wounds. The basic mechanisms of skin wound repair were influenced by the treatment modality as demonstrated by the observed differences in granulation tissue formation, reepithelialization, and rate of wound contraction. (Plast. Reconstr. Surg. 106: 602, 2000.)

Medical 3D Printing for the Radiologist

While use of advanced visualization in radiology is instrumental in diagnosis and communication with referring clinicians, there is an unmet need to render Digital Imaging and Communications in Medicine (DICOM) images as three-dimensional (3D) printed models capable of providing both tactile feedback and tangible depth information about anatomic and pathologic states. Three-dimensional printed models, already entrenched in the nonmedical sciences, are rapidly being embraced in medicine as well as in the lay community. Incorporating 3D printing from images generated and interpreted by radiologists presents particular challenges, including training, materials and equipment, and guidelines. The overall costs of a 3D printing laboratory must be balanced by the clinical benefits. It is expected that the number of 3D-printed models generated from DICOM images for planning interventions and fabricating implants will grow exponentially. Radiologists should at a minimum be familiar with 3D printing as it relates to their field, including types of 3D printing technologies and materials used to create 3D-printed anatomic models, published applications of models to date, and clinical benefits in radiology. Online supplemental material is available for this article.

A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Restoration of Facial Form and Function After Severe Disfigurement from Burn Injury by a Composite Facial Allograft

Composite facial allotransplantation is emerging as a treatment option for severe facial disfigurements. The technical feasibility of facial transplantation has been demonstrated, and the initial clinical outcomes have been encouraging. We report an excellent functional and anatomical restoration 1 year after face transplantation. A 59‐year‐old male with severe disfigurement from electrical burn injury was treated with a facial allograft composed of bone and soft tissues to restore midfacial form and function. An initial potent antirejection treatment was tapered to minimal dose of immunosuppression. There were no surgical complications. The patient demonstrated facial redness during the initial postoperative months. One acute rejection episode was reversed with a brief methylprednisolone bolus treatment. Pathological analysis and the donors medical history suggested that rosacea transferred from the donor caused the erythema, successfully treated with topical metronidazol. Significant restoration of nasal breathing, speech, feeding, sensation and animation was achieved. The patient was highly satisfied with the esthetic result, and regained much of his capacity for normal social life. Composite facial allotransplantation, along with minimal and well‐tolerated immunosuppression, was successfully utilized to restore facial form and function in a patient with severe disfigurement of the midface.

Routine use of wound vacuum-assisted closure does not allow coverage delay for open tibia fractures.

Background: Prevention of infection is a paramount concern after open fracture of the tibia. Previous studies have shown that delay in soft-tissue coverage may raise infection rates. Use of vacuum-assisted closure devices in open fracture wounds has become common. The authors analyzed whether use of the vacuum-assisted closure sponge can allow delay of flap coverage for open tibia fractures without an increase in infection rate. Methods: The authors identified 38 patients with Gustilo grade IIIB open fractures from their trauma registry with a minimum 1-year follow-up. From the medical record, the authors collected information on the time from injury to definitive wound coverage, type of fixation, type of coverage, and demographics. Infected patients were defined as patients that required surgical debridement after coverage with positive cultures. Results: Patients who underwent definitive coverage within 7 days had a significantly decreased rate of infection (12.5 percent) compared with patients who had coverage at 7 days or more after injury (57 percent) (p < 0.008). The overall infection rate was 36 percent with routine use of the vacuum-assisted closure sponge. Patients who developed infection had a greater mean time to coverage than patients who did not develop infection (8.9 days versus 4.8 days; p < 0.029). Conclusions: Routine use of vacuum-assisted closure with open tibia fractures is safe and provides a good primary dressing over open wounds. For Gustilo grade IIIB tibia fractures, vacuum-assisted closure therapy does not allow delay of soft-tissue coverage past 7 days without a concomitant elevation in infection rates.

Tissue Engineering of Skin

The skin plays a crucial role in protecting the integrity of the bodys internal milieu. The loss of this largest organ is incompatible with sustained life. In reconstructive surgery or burn management, substitution of the skin is often necessary. In addition to traditional approaches such as split- or full-thickness skin grafts, tissue flaps and free-tissue transfers, skin bioengineering in vitro or in vivo has been developing over the past decades. It applies the principles and methods of both engineering and life sciences toward the development of substitutes to restore and maintain skin structure and function. Currently, these methods are valuable alternatives or complements to other techniques in reconstructive surgery. This review article deals with the evolution and current approaches to the development of in vitro and in vivo epidermis and dermis.

Vascular considerations in composite midfacial allotransplantation.

Background: Advances in microsurgery and immunosuppression have allowed for facial reconstruction at a qualitatively new level with facial composite tissue allografts. Although donor tissue recovery is unique for each patient, transplantation of the maxilla and overlying soft tissues will be a frequent indication. Vascularity of the maxilla and palate, supplied by facial arteries alone, has been a concern. Based on cadaver dissections and a clinical case, vascular considerations for transplantation of the entire midface are discussed. Methods: To prepare for central facial transplantation in an identified patient, a preclinical dissection was completed on four cadavers. In April of 2009, an extended midfacial allotransplantation was performed. The flap included the entire group of facial mimetic muscles with overlying skin, sensory and motor nerves, nose, upper lip, maxilla, teeth, and hard palate. Results: The preclinical study identified key anatomical structures for inclusion in the composite tissue allograft. Moreover, dissections showed that the facial and angular blood vessels were connected to branches of the maxillary vessels through an anastomotic network organized around the periosteum and bony canals of the midfacial skeleton. Transplantation of a central face allograft including the maxilla and palate was anticipated to be feasible. A technically successful clinical case was completed. Conclusions: Anatomical and clinical observations elucidated several technical points related to composite tissue transplantation of the midface. Careful graft harvest, appropriate selection of donor and recipient vessels, complete allograft revascularization, and restoration of sensory and motor function are critical to making face transplant surgery safe and functional.

The Management of Antibody‐Mediated Rejection in the First Presensitized Recipient of a Full‐Face Allotransplant

We report on the management of the first full‐face transplantation in a sensitized recipient with a positive preoperative crossmatch and subsequent antibody‐mediated rejection (AMR). The recipient is a 45‐year‐old female who sustained extensive chemical burns, with residual poor function and high levels of circulating anti‐HLA antibodies. With a clear immunosuppression plan and salvage options in place, a full‐face allotransplant was performed using a crossmatch positive donor. Despite plasmapheresis alongside a standard induction regimen, clinical signs of rejection were noted on postoperative day 5 (POD5). Donor‐specific antibody (DSA) titers rose with evidence of C4d deposits on biopsy. By POD19, biopsies showed Banff Grade III rejection. Combination therapy consisting of plasmapheresis, eculizumab, bortezomib and alemtuzumab decreased DSA levels, improved clinical exam, and by 6 months postop she had no histological signs of rejection. This case is the first to demonstrate evidence and management of AMR in face allotransplantation. Our findings lend support to the call for an update to the Banff classification of rejection in vascularized composite tissue allotransplantation (VCA) to include AMR, and for further studies to better classify the histology and mechanism of action of AMR in VCA.