AlloDerm Research Articles

Tracheal Surgery: Posterior Splinting Tracheoplasty for Tracheomalacia

Adult acquired tracheomalacia is an uncommon disorder that is more frequently diagnosed by CT imaging than by presenting associated symptoms. Common symptoms include dyspnea, constant coughing, inability to raise secretions and recurrent respiratory infections. The basic evaluation includes an inspiratory-expiratory chest CT (Dynamic CT), an awake functional bronchoscopy and pulmonary function studies. Patients with significant associated symptoms and severe collapse on CT and bronchoscopy are offered an operation. Tracheoplasty (or more commonly tracheobronchoplasty) is performed via a high right thorocotomy. The posterior airway is exposed after the azygous vein is ligated. The posterior wall of the trachea is reefed to a sheet of acellular dermis (or polypropylene mesh) with a series of 4 mattress sutures of 4-0 sutures from the thoracic inlet to the bottom of the trachea to re-shape the trachea and restore the normal D shape. Similar techniques are performed if the main bronchi are involved. Patients report generally good results with relief of their symptoms. Functional capacity is improved while pulmonary function tests usually are not.

Use of Acellular Fish Skin for Dura Repair in an Ovine Model: A Pilot Study

Recently the use of biologic materials as dura mater repair patches has been increasing. The purpose of this study is to assess the basis for efficacy and safety of using a novel fish derived acellular dermis (Kerecis Omega3 DuraTM). In an ovine model a craniotomy under general anaesthesia was performed. A defect was produced in the dural covering of approximately 1 × 2 cm and closed with an onlay technique, with Kerecis Omega3 Dura. The bone defect was covered with the bony flap and the overlying tissues closed in layers. At 2, 5, 8 and 11 weeks the sheep underwent MRI scanning followed by euthanasia, necropsy and histological assessment. MRI images taken at 2, 5, 8 and 11 weeks showed initially moderate inflammatory response, which diminished over time, and at 11 weeks no evidence of inflammation existed. There was evidence of cerebrospinal fluid leakage at no time point. Necropsy revealed some adhesions at 5 and 8 weeks, in particular at 5 weeks, but at 11 weeks there were no adhesions found. From 2 - 11 weeks, there was evidence of initially an inflammatory reaction followed by neodura formation at the defect site through cellular ingrowth and remodeling of the acellular fish skin. Histology showed a histiocytic foreign body reaction initially that subsided over time. As early as 8 weeks there was evidence of neodura formation and by 11 weeks there was a minimal inflammatory response with an intact neodura formed. In this pilot study the Kerecis Omega3 Dura patches performed in a safe and efficacious manner. This new material needs to be fully assessed and compared with other products that are currently on the market in a larger scale animal study.

The impact of chemotherapy and radiation therapy on the remodeling of acellular dermal matrices in staged, prosthetic breast reconstruction.

An acellular dermal matrix will typically incorporate, in time, with the overlying mastectomy skin flap. This remodeling process may be adversely impacted in patients who require chemotherapy and radiation, which influence neovascularization and cellular proliferation. Multiple biopsy specimens were procured from 86 women (n = 94 breasts) undergoing exchange of a tissue expander for a breast implant. These were divided by biopsy location: submuscular capsule (control) as well as superiorly, centrally, and inferiorly along the paramedian acellular dermis. Specimens were assessed for cellular infiltration, cell type, fibrous encapsulation, scaffold degradation, extracellular matrix deposition, neovascularization, mean composite remodeling score, and type I and III collagen. Patients were compared based on five oncologic treatment groups: no adjuvant therapy (untreated), neoadjuvant chemotherapy with or without radiation, and chemotherapy with or without radiation. Biopsy specimens were procured 45 to 1805 days after implantation and demonstrated a significant reduction in type I collagen over time. Chemotherapy adversely impacted fibrous encapsulation (p = 0.03). Chemotherapy with or without radiation adversely impacted type I collagen (p = 0.02), cellular infiltration (p < 0.01), extracellular matrix deposition (p < 0.04), and neovascularization (p < 0.01). Radiation exacerbated the adverse impact of chemotherapy for several remodeling parameters. Neoadjuvant chemotherapy also caused a reduction in type I (p = 0.01) and III collagen (p = 0.05), extracellular matrix deposition (p = 0.03), and scaffold degradation (p = 0.02). Chemotherapy and radiation therapy limit acellular dermal matrix remodeling. Therapeutic, III.

Healing septal perforations by secondary intention using acellular dermis as a bioscaffold.

Several techniques are described in the literature for nasal septal perforation repair. Most of these involve interposition grafts in conjunction with local pedicled mucosal flaps. The following article describes our experience using acellular dermis as a bioscaffold to support the regrowth of nasal septal mucosa by secondary intention. Retrospective chart review of all patients who underwent repair of nasal septal perforations by the senior author using acellular dermis placed between the 2 sides of the perforation and covered with silastic splints to allow for mucosalization. Thirteen patients underwent nasal septal perforation repair using this technique. All perforations repaired were under 2 cm in greatest dimension. Two-thirds of patients had complete closure of the perforation upon initial use of bioscaffolding technique. The remaining third achieved near-total closure with bioscaffolding technique and were able to be completely closed with a single additional procedure. Acellular dermis offers an alternative to most currently described complex flaps. The method can be used in patients with defects less than 2 cm, but initial data suggest caution when using in those with wound healing impediments. This technique is also an excellent choice for patients with multiple small septal perforations.

Cell Therapy for Dermal Reconstruction

Skin is the largest organ of human which plays a critical role in different functions of the human body, such as homeostasis, sensory detection, protecting against external insults, and healing. Skin is consisted of thin epidermis and relatively acellular dermis of collagenrich extracellular matrix (ECM) (1). One of the major applications of tissue-engineered skin substitutes in wound healing is to promote cutaneous wound healing. The skin wounds can be caused by mechanical trauma, surgical procedures, reduced blood circulations, burns, or aging procedures. Most of the skin wounds can heal naturally, but additional surgery requires immediate coverage, using skin substitutes, to facilitate skin repair and regeneration, in cases with extensive or irreversible skin damages (2). However, the available skin substitutes often cause a range of problems including wound contraction, scar formation, and poor integration to the underlying host. Engineering the skin substitutes through tissue engineering approaches has relied upon the creation of three-dimensional scaffolds to guide cell adhesion, growth, and differentiation to form functional and structural tissues (3). The scaffolds not only cover the wounds and provide a physical barrier against external infection, but also provide support both for dermal fibroblasts and the overlying keratinocytes. A good tissue scaffold should exhibit appropriate physical and mechanical characteristics and should have appropriate surface chemical and nanoand microstructures to facilitate cellular attachment, proliferation, and differentiation (4). The composition of fibroblastkeratinocyte is formed based on the membrane with the promoted three dimensions, which can produce skin equivalent, and promising in vitro results suggested the potential application of these for the treatment of burns and chronic wounds. Significant improvements have been made to identify and to locate the stem cells in the skin. Several studies have proved that stem cells can be used for skin reconstitution in healing the skin wounds. The limited regenerative capacity of epidermal keratinocytes could be overcome by self-renewing keratinocyte stem cells. Locating hair follicle stem cells can bring possible hope to form hair follicle in future bioengineered skin products (5). However, there are still many challenges that are collectively faced by bioengineers, cell biologists and clinicians; further development in this area needs ongoing interactions and collaborations. New technologies are being developed to provide hope for future regenerative skin technologies. Stem cell technology is making new milestones in the efficiency of cell culturing.

Acellular Dermis Obtainment to Fibroblastic Cell Culture and Tissue Engineering

Tissue injuries are the main factors that lead to treatment by skin culture. In cases where the damage is extensive patient has insufficient amount of tissue to recover the area lost. A possible solution is the use of tissue engineering. Dermal substitutes must provide features and functions as close as possible to the normal skin. The acellular dermis can be obtained from the own patient and represents a viable alternative as a graft. The acellular dermis is used as a dermal analogue to the implantation of cells for tissue engineering treatment. The aim of this study was to compare different ways of obtaining mouse skin acellular dermis and characterize this dermis by macroscopic visualization, light and atomic force microscopy and cell culture.

Endoscopic Anterior Skull Base Resection: University of Miami Experience

Objectives: To report: (1) Oncological safety of endoscopic technique using disease free survival and a Kaplan Maier analysis for malignant tumors and recurrence rate for benign tumors; (2) Type of reconstruction of large anterior skull base defects and rate of postoperative cerebrospinal fluid leak; (3) Postoperative major (cranial and orbital) and minor complications. Methods: Retrospective chart review identifying patients undergoing endoscopic anterior skull base resection for malignant and benign tumors at a tertiary care medical center between September 1997 and June 2013. Results: Preliminary analysis shows that 34 patients underwent transnasal endoscopic resection for malignant disease and 2 patients for benign disease. The median follow-up was 30 months. Olfactory neuroblastoma was the most common pathology. There were 3 major and 5 minor complications. Three patients recurred locally resulting in a local control rate of 90.9%. The overall mortality rate was 18%, and the disease specific mortality was 3%. Reconstruction of the skull base defect was done using acellular dermis as a sole graft with a success rate of 97% and a cerebrospinal fluid leak in 1 case. Conclusions: Endoscopic anterior skull base resection for benign or malignant disease is a safe and valid alternative compared to standard approaches. It is gaining more popularity, and with increasing surgical expertise, the indications of this procedure are expanding.

Glyaderm® dermal substitute: Clinical application and long-term results in 55 patients

IntroductionGlycerol preserved acellular dermis (Glyaderm®) consists of collagen and elastin fibers and is the first non-profit dermal substitute derived from glycerol-preserved, human allogeneic skin. It is indicated for bi-layered skin reconstruction of full thickness wounds. MethodsA protocol for clinical application and optimal interval before autografting with split thickness skin graft (STSG) was developed in a pilot study.A phase III randomized, controlled, paired, intra-individual study compared full thickness defects engrafted with Glyaderm® and STSG versus STSG alone.Outcome measures included percentage of Glyaderm® take, STSG take, and scar quality assessment. ResultsPilot study (27 patients): Mean take rates equaled 91.55% for Glyaderm® and 96.67% for STSG. The optimal autografting interval was 6 days (±1 day).Randomized trial (28 patients): Mean Glyaderm® take rate was 88.17%. STSG take rates were comparable for both research groups (p=0.588). One year after wound closure, Glyaderm®+STSG was significantly more elastic (p=0.003) than STSG alone. Blinded observers scored Glyaderm® treated wounds better in terms of scar quality. DiscussionThe efficacy of Glyaderm® as a suitable dermal substitute for full thickness wounds is attested. Currently a procedure for simultaneous application of Glyaderm® and STSG is adopted, allowing for further widespread use of Glyaderm®.

Acellular dermal matrices and radiotherapy in breast reconstruction: a systematic review and meta-analysis of the literature.

The increasing use of commercially available acellular dermis matrices for postmastectomy breast reconstruction seems to have simplified the surgical procedure and enhanced the outcome. These materials, generally considered to be highly safe or with only minor contraindications due to the necessary manipulation in preparatory phases, allow an easier one-phase surgical procedure, in comparison with autologous flaps, offering a high patient satisfaction. Unfortunately, the claim for a higher rate of complications associated with irradiation at the implant site, especially when the radiation therapy was given before the reconstructive surgery, suggested a careful behaviour when this technique is preferred. However, this hypothesis was never submitted to a crucial test, and data supporting it are often discordant or incomplete. To provide a comprehensive analysis of the field, we searched and systematically reviewed papers published after year 2005 and registered clinical trials. On the basis of a meta-analysis of data, we conclude that the negative effect of the radiotherapy on the breast reconstruction seems to be evident even in the case of acellular dermis matrices aided surgery. However, more trials are needed to make solid conclusions and clarify the poor comprehension of all the factors negatively influencing outcome.

Comparison of Outcomes Using AlloDerm Versus FlexHD for Implant-Based Breast Reconstruction

Prosthetic reconstruction using human acellular dermis (ADM) is a common practice in breast reconstruction. AlloDerm and FlexHD are two different forms of ADM, each with unique characteristics. No studies have directly compared the postoperative complications of these 2 products. The outcomes of 547 consecutive implant-based breast reconstructions were reviewed. Reconstruction was performed in 382 consecutive women (547 total breasts), employing mostly immediate reconstruction (81%). Mean follow-up was 6.4 months. Among immediate reconstructions, 165 used AlloDerm and 97 used FlexHD. Complications were similar by univariate analysis. In multivariate analysis, smoking and higher initial implant fill were risk factors for delayed healing. The use of FlexHD, single-stage reconstruction, and smoking were independent risk factors for implant loss. There is no significant difference in the complication rates between AlloDerm and FlexHD in immediate breast reconstruction. Multivariate analysis suggests that FlexHD may be a risk factor for implant loss.

A Novel Use of Human Acellular Dermis for Conduit Salvage After Esophagectomy

Postesophagectomy anastomotic leaks cause significant morbidity and mortality. Esophageal diversion is often required when extensive tissue loss precludes primary repair. We describe a technique in which human acellular dermis (AlloDerm) is used to repair the conduit, and report a series of 3 patients with significant anastomotic dehiscence whose conduits were salvaged using this technique.

Lip and palatine cleft surgery outcome is improved by the adjunvant use of acellular swine dermis and umbilical cord blood stem cells (UCB SC)

Lip and palatine cleft surgery outcome is improved by the adjunvant use of acellular swine dermis and umbilical cord blood stem cells (UCB SC)

Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting

BackgroundThe use of human acellular dermis (hAD) to close open abdomen in the treatment process of severe peritonitis might be an alternative to standard care. This paper describes an investigation of the effects of fluids simulating an open abdomen environment on the biomechanical properties of Epiflex® a cell-free human dermis transplant.MethodshAD was incubated in Ringers solution, blood, urine, upper gastrointestinal (upper GI) secretion and a peritonitis-like bacterial solution in-vitro for 3 weeks. At day 0, 7, 14 and 21 breaking strength was measured, tensile strength was calculated and standard fluorescence microscopy was performed.ResultshAD incubated in all five of the five fluids showed a decrease in mean breaking strength at day 21 when compared to day 0. However, upper GI secretion was the only incubation fluid that significantly reduced the mechanical strength of Epiflex after 21days of incubation when compared to incubation in Ringer’s solution.ConclusionhAD may be a suitable material for closure of the open abdomen in the absence of upper GI leakage and pancreatic fistulae.

In vitro study of Biofilm Growth on Biologic Prosthetics

Biologic prosthetics are increasingly used for the repair of abdominal wall hernia defects but can become infected as a result of peri- or early post-operative bacterial contamination. Data evaluating biofilm formation on biologic prosthetics is lacking. The aim of this study was to investigate the influence of different biologic prosthetics on the growth behavior of two different bacterial species and their ability to form biofilms. Methicillin resistant Staphylococcus aureus (MRSA) or Pseudomrnonas aeruginosa were incubated on disks of two biologic prosthetics-human acellular dermis (ADM), and porcine small intestinal submucosa (SIS). The bacteria were allowed to attach to the prosthetics and propagate into mature biofilms for 24 hours at 370C. Images of biofilms were obtained using confocal microscopy and scanning electron microscopy (SEM). The number of viable cells and the biofilm biomass were quantified by colony forming units (CFUs) and crystal violet staining respectively. Analysis of variance was performed to compare the mean values for the different prosthetics. Each biologic matrix had a distinct surface characteristic. SEM visualized mature biofilms characterized by highly organized multi-cellular structures on surface of both biologic prosthetics. Quantification of bacterial growth over time showed that ADM had the lowest CFUs and biofilm biomass at 24 hours post-inoculation compared to SIS for both bacterial strains. MRSA and P. aeruginosa can form mature biofilms on biologic prosthetics but the relative abundance of the biofilm varies on different prosthetic constructs. Biologic material composition and manufacturing methods may influence bacterial adherence.

Autologous Dermal Grafts as Posterior Lamellar Spacers in the Management of Lower Eyelid Retraction

To determine the safety and efficacy of autologous postauricular dermal grafts as posterior lamellar spacing material in patients with lower eyelid retraction. At a tertiary care institution, 10 eyelids of 10 patients (7 men, 3 women; mean 56 years, range 24-78) who underwent repair of lower eyelid retraction using a postauricular dermal graft between July 2008 and December 2010 were retrospectively assessed. Data collected included patient demographics, etiology of retraction, and surgical history. Outcome measures included preoperative and postoperative eyelid position and surgery-related complications. Postoperative results were favorable: mean preoperative inferior scleral show was 3.3 ± 2.6 mm compared with 0.3 ± 1.2 mm postoperatively, p = 0.004 (paired t test). Mean follow up was 39.2 weeks (range 12-94). Complications included keratinization of the graft with vellus hair growth (n = 1) and ectropion (n = 1), both corrected with minor surgical interventions. One patient achieved overcorrection but declined further treatment. No donor site complications were encountered. These data suggest postauricular dermal grafts are effective posterior lamellar spacers in the correction of eyelid retraction. They have adequate rigidity whilst maintaining sufficient pliability to mold to the globe. Resorption, common to acellular dermis matrix allografts and xenografts, was not encountered. Donor site complications were not encountered. Complications shared with other material include overcorrection and ectropion. Complications unique to autologous dermis include keratinization and hair growth.

The Versatility of Acellular Fetal Bovine Dermal Matrix for Head and Neck Surgical Reconstruction in Children

Objectives: To describe the versatility of acellular fetal bovine dermal matrix as an alternative to human cadaveric allograft for head and neck reconstructive procedures in children. Study Design: Case series with chart review. Methods: A database of pediatric operative procedures was queried for the use of acellular fetal bovine dermal matrix over a 16-month period. Indications for reconstruction were assessed and initial parental and surgeon satisfaction with the product were noted. Results: During the time period of 3/2012 and 7/2013 a total of 8 reconstructive procedures were performed on pediatric patients using acellular fetal bovine dermal matrix. Indications for use varied and included open and transnasal endoscopic repair of encephaloceles and soft tissue reconstructions including lateral pharyngeal wall repair, cleft palate repair, and facial recontouring operations. Acellular fetal bovine dermal matrix had a subjectively increased ease of use as compared to the surgeon’s prior experience with human cadaveric acellular dermis. Every parent vocalized a greater comfort level with the use of a bovine product over the alternative of human cadaveric tissue. The cost of acellular fetal bovine dermal matrix is slightly lower than the cost of human cadaveric acellular dermis. Conclusions: Acellular fetal bovine dermal matrix appears to be an acceptable alternative to human cadaveric acellular dermis for various forms of head and neck soft tissue reconstruction in children. Further prospective studies are warranted to assess for any differences in the long-term efficacy of this product as compared to other forms of allograft reconstruction.

Research progress of tissue-engineered oral mucosa

Large area defect of intra-oral or extra-oral mucosa caused by mucosa lesions need suitable graft materials for repair.Tissue engineering methods can provide effective pathway to resolve this problem.Furthermore,full thickness mucosa equivalent constructed by tissue engineering methods also can be used as a model to evaluate dental materials,drug delivery system and oral carcinogenesis.Basic issues of tissue-engineered mucosa including sources of seed cells,scaffold materials such as de-epidermised acellular dermis,collagens,fibrin glue and biomacromolecule electrostatic spinning are discussed in this review,and the application researches of tissueengineered mucosa for mucosa reconstruction and mucosa model equivalents are expounded too. Key words: Oral mucosa; Tissue engineering; Transplantation; Model; Squamous cell carcinoma

Porcine Acellular Dermis–Assisted Breast Reconstruction

Background:Implant-based reconstruction is the most frequently performed breast reconstruction procedure. A persistent issue with this approach is optimizing outcomes in the setting of radiotherapy. Experimental evidence suggests that acellular dermal matrix use may provide a protective benefit, but clinical evidence is lacking. The purpose of this study was to assess postoperative complications and the effect of radiotherapy on complications and outcomes in women who underwent immediate, porcine acellular dermal matrix (PADM, Strattice)-assisted, implant-based breast reconstruction postmastectomy.Methods:Patients with at least 1 year of follow-up were included in this retrospective study. Patient charts were reviewed for demographic data, adjunctive therapy use, duration of follow-up, and type and incidence of complications during follow-up.Results:A total of 158 reconstructions were performed in 103 patients. Adjuvant therapy included chemotherapy in 51% of patients and radiotherapy in 25% of breasts. Mean follow-up was 36.2 months. Complications occurred in 17 breasts (10.8%): implant/expander loss (8.2%); infection (5.7%); dehiscence (3.8%); eschar (1.9%); and ischemia, hematoma, and seroma (0.6% each). Nine breasts with complications had been irradiated; all were irradiated prereconstruction. Rate of total complications, implant/expander loss, and dehiscence was significantly higher in irradiated breasts. Breasts irradiated postreconstruction had no complications.Conclusions:Addition of PADM to implant-based reconstruction is associated with acceptable complication rates comparable to those observed with standard submuscular reconstructions. Complications are increased in the setting of radiotherapy; but PADM use may protect against the adverse effects of postreconstruction radiotherapy.

Remodeling of the basement membrane during the healing process after intraoral grafting of tissue-engineered human oral mucosa in athymic mice

Background and objective: An ex vivo-produced oral mucosa equivalent (EVPOME) is composed of a stratified layer of human oral keratinocytes seeded onto a human acellular dermis, AlloDerm®. Our preliminary clinical study showed the EVPOME grafts had enhanced maturation of the underlying submucosal layer associated with rapid epithelial coverage. Results of our animal study suggested that grafting of the EVPOME onto an oral wound promotes re-epithlialization of oral mucosa in the healing process. The objective of the present study was to investigate the change in the basement membrane of EVPOME during the healing process after intraoral grafting in athymic mice.

Analysis of Clinically Significant Seroma Formation in Breast Reconstruction Using Acellular Dermal Grafts

With a rise in tissue expander-based breast reconstructions (TEBRs) using acellular dermal matrix (ADM), we have seen an increase in ADM-specific complications. In this study, we aimed to evaluate clinically significant seroma (CSS) formation-defined by the need for a drainage procedure-to determine if there was a difference in incidence between product types: AlloDerm (AL), DermaMatrix (DM), and FlexHD (FHD). This was a retrospective review of consecutive patients who underwent TEBR at a single institution. The total number of reconstructed breasts was separated into the following 4 groups according to the product type: AL, DM, FHD, or no ADM. We identified the total number of CSSs and compared these data between product types. A logistic regression was performed in an attempt to identify independent risk factors associated with seroma formation. In total, we identified 284 consecutive TEBRs. Overall, there were 17 (7.7%) seromas in 220 breast reconstructions in which ADM was used. When comparing the number of CSS between groups-AL (n = 2, 4.0%), DM (n = 6, 5.4%), FHD (n = 9, 14.75%), and no ADM (n = 1, 1.5%)-we found a significant difference in seroma incidence between product types (P = 0.016). Multivariate analysis identified a strong trend toward FHD as an independent predictor of seroma formation (P = 0.061). Our review suggests that there is strong trend in CSS formation with the use of FHD as compared to other product types and reconstructions in which no ADM was used.