Dural Regeneration Research Articles

Electrospun Nanofibers for Dura Mater Regeneration: A Mini Review on Current Progress.

Dural defects are a common problem in neurosurgical procedures and should be repaired to avoid complications such as cerebrospinal fluid leakage, brain swelling, epilepsy, intracranial infection, and so on. Various types of dural substitutes have been prepared and used for the treatment of dural defects. In recent years, electrospun nanofibers have been applied for various biomedical applications, including dural regeneration, due to their interesting properties such as a large surface area to volume ratio, porosity, superior mechanical properties, ease of surface modification, and, most importantly, similarity with the extracellular matrix (ECM). Despite continuous efforts, the development of suitable dura mater substrates has had limited success. This review summarizes the investigation and development of electrospun nanofibers with particular emphasis on dura mater regeneration. The objective of this mini-review article is to give readers a quick overview of the recent advances in electrospinning for dura mater repair.

In vivo evaluation of bilayer ORC/PCL composites in a rabbit model for using as a dural substitute

ABSTRACT Objective After a neurosurgical procedure, dural closure is commonly needed to prevent cerebrospinal fluids (CSF) leakage and to reduce the risk of complications, including infections and chronic inflammatory reactions. Although several dural substitutes have been developed, their manufacturing processes are complicated and costly and that many of them have been implicated in causing postoperative complications. This study aimed to assess the effectiveness and safety of new bilayer ORC/PCL composites in a rabbit model. Methods Two formulations of bilayer oxidized regenerated cellulose (ORC)/poly ε-caprolactone (PCL) knitted fabric-reinforced composites and an autologous graft (pericranium) were employed for dural closure in forty-five male rabbits. Systemic reaction and the local reaction of the samples were assessed and compared at one-, three- and six-months post-implantation by blood chemistry and gross, and microscopic assessment using hematoxylin-eosin and Masson’s trichrome stains. Results No signs of CSF leakage or systemic infection were seen for all samples. All samples demonstrated minimal adhesion to adjacent tissues. The degree of host fibrous connective tissue ingrowth into both composites was comparable to that of the autologous group, but bone formation and osteoclast activities were significantly greater. Both composites progressively degraded over times and the residual thickness of the nonporous layer was 50% of the initial thickness at six months post-implantation. Discussion Bilayer ORC/PCL composites were successfully employed for dural closure in the rabbit model. They were biocompatible and could support dural regeneration comparable to that of the autologous group, but induced greater osteogenesis.

Operative Management of Idiopathic Spinal Cord Herniation: Case Series and Novel Technique for Repair of Recurrent Herniation

Idiopathic spinal cord herniation (ISCH) is a rare pathology of the spine defined by herniation of the spinal cord through a dural defect. To highlight the operative management of ISCH and the surgical nuances of ISCH repairs conducted at our institution. This retrospective review examines consecutive patients with ISCH who were treated surgically between January 1, 2010, and July 31, 2017, at Barrow Neurological Institute, Phoenix, Arizona. Four patients with ISCH presented with thoracic myelopathy and lower extremity weakness during the study period. Treatment consisted of reduction of the herniated spinal cord and filling of the dural defect with a collagen-based dural regeneration matrix. In 3 patients the dural edges were covered with a collagen-matrix intradural sling, and in 1 patient they were repaired primarily with interrupted sutures. Three of the 4 patients experienced improvement in myelopathic symptoms; the fourth patient suffered neurological decline in the immediate postoperative period. ISCH is a complex pathological condition likely to result in progressive myelopathy. Surgery offers patients the possibility of stabilizing the progression of the spinal cord dysfunction and perhaps restoring neurological function. However, extreme care must be taken during surgery to minimize manipulation of the fragile herniated cord.

Efficacy and safety of small intestinal submucosa in dural defect repair in a canine model

Dural defects are a common problem, and inadequate dural closure can lead to complications. Several types of dural substitute materials have recently been discarded or modified owing to poor biocompatibility or mechanical properties and adverse reactions. The small intestinal submucosa (SIS) is a promising material used in a variety of applications. Based on the limitations of previous studies, we conducted an animal study to evaluate the efficacy and safety of the SIS in preclinical trials. Twenty-four male beagle dogs were subjected to surgical resection to produce dural defects. SIS or autologous dural mater was patched on the dural defect. Gross and histological evaluations were carried out to evaluate the efficacy and safety of the therapy. Our findings demonstrated that the SIS, which stimulated connective and epithelial tissue responses for dural regeneration and functional recovery without immunological rejection, could provide prolonged defect repair and prevent complications. The mechanical properties of the SIS could be adjusted by application of multiple layers, and the biocompatibility of the material was appropriate. Thus, our data suggested that this material may represent an alternative option for clinical treatment of dural defects.

Comparative study of fibrin and chemical synthetic sealant on dural regeneration and brain damage

Object Several materials, such as polyethylene glycol (PEG) hydrogel and fibrin glue, have been used to seal dural incisions after brain and spinal surgeries. Although the use of PEG sealant is gaining popularity, it can be associated with postoperative cerebrospinal fluid leakage and infection. However, the reasons for this association are currently unknown. The present study aimed to investigate the effects of PEG sealant and fibrin glue on wound healing and brain damage in vivo. Methods Oval-shaped bone defects and dural defects were created bilaterally over the parietal lobes of 22 Japanese white rabbits. The dural defects were covered with 0.5 ml of fibrin glue on one side and 0.5 ml of PEG sealant on the other side. Dural regeneration and brain damage were investigated in each harvested brain and dura mater using light microscopy. Results Dural regeneration was more effective in the presence of fibrin glue than it was with PEG sealant (p = 0.014). Of the 22 rabbits, 11 showed thick (Grades ++ and +++) dural regeneration by 28 days postsurgery in the hemisphere where fibrin glue was used, whereas Grade +++ dural regeneration was not observed in the PEG hydrogel hemisphere, and only 4 rabbits showed Grade ++ regeneration. Abscess and granulation formation also tended to be more severe when PEG hydrogel sealant was used. No Grade ++ granulation/abscess formation was observed with fibrin glue, and Grade + was only observed in 13 of 22 rabbits. Conversely, with PEG hydrogel sealant, only 2 rabbits did not show granulation/abscess formation, and Grade +, ++, and +++ granulation/abscess formation was observed in 8, 7, and 5 rabbits, respectively. The extent of cortical damage was significantly greater in rabbits with abscesses and granulations, compared with rabbits without these lesions (p = 0.007). Conclusions Dural regeneration tended to occur more rapidly with fibrin glue, whereas granulation was more likely with PEG hydrogel sealant, which led to postoperative complications. Histological analysis indicated that PEG hydrogel sealant inhibited the normal tissue healing process and that outcomes were improved by the use of fibrin glue.

Use of a collagen biomatrix (TissuDura®) for dura repair: a long-term neuroradiological and neuropathological evaluation

The aim of this study was to evaluate the clinical, neuroradiological, and neuropathological outcomes of patients treated with equine collagen foil (TissuDura) as a dura mater substitute during cranial and spinal neurosurgical procedures. All patients treated at the Department of Neurosurgery of the Second University of Naples with TissuDura between 2005 and 2009 were included. Dural reconstruction was performed using TissuDura, overlaid 1 cm over the dural defect with additional fixation using fibrin glue. No surgical sutures were used. Patients underwent postoperative contrast-enhanced magnetic resonance scans at 1 week, 1 month, and 1 year after surgery to detect any cerebrospinal fluid (CSF) leaks, infections, inflammations, or CSF circulation in the surgical region. Dural reconstruction was performed in 74 patients, including 50 patients with tumors, two with C2 neurinoma, two with acoustic neurinoma, six with Chiari I malformation, two with severe head injury, and 12 requiring spinal surgery. Clinical and neuroradiological findings were normal and no signs of graft rejection or CSF leaks at postoperative follow-up were observed. In two cases of atypical meningioma, re-operation of the dural reconstruction was performed after 1 year. No adherences between brain and neodura were detected, and histopathological investigations demonstrated dural regeneration. Following dural reconstructions with TissuDura without surgical sutures, no local toxicity or complications were observed for up to 1 year. TissuDura demonstrated elasticity, non-reactivity, and good adaptability. The overlay technique using fibrin glue was simple and fast. Future studies and longer follow-up are needed to confirm the efficacy of TissuDura.

Novel Equine Collagen-only Dural Substitute

A watertight and meticulous dural closure is an essential step after intradural neurosurgical procedures. When such a task cannot be performed, dural replacement materials and other adjunctive measures can provide an effective barrier between the subarachnoid compartment and the extradural space. We present our experience with a novel collagen-derived dural substitute in a series of 114 patients undergoing a variety of neurosurgical procedures. The patients were clinically or neuroradiologically observed, for immediate and delayed local or systemic complications related to the implant. In three patients who underwent reoperation after decompressive duraplasty and craniectomy for bone flap repositioning, we performed biopsy of the dural implant for histopathological studies. None of the patients experienced local or systemic complications or toxicity related to the dural patch. None of the patients experienced a postoperative cerebrospinal fluid fistula, except one patient who underwent an endoscopic endonasal transsphenoidal marsupialization of a large intrasuprasellar arachnoid cyst; the fistula required reoperation for cerebrospinal fluid fistula repair and intravenous antibiotic therapy for bacterial meningitis. Postoperative magnetic resonance imaging scans showed signs of severe inflammatory response in only one patient who did not present any postoperative clinical symptom or neurological deficits. Three patients underwent reoperation for bone flap repositioning after decompressive craniectomy; in all patients, the dural substitute appeared to have promoted satisfactory dural regeneration, as confirmed by the histological studies. Furthermore, in such patients, no or minimal adherence with the other tissues and the brain cortex was observed. This study demonstrates that the new collagen-only biomatrix is a safe and effective dural substitute for routine neurosurgical procedures. The absence of local and systemic toxicity or complications and the scarce promotion of adherences and inflammation make this material appealing for its use as a dural substitute, even in cases in which the necessity of reoperation is foreseen.

Collagen-only biomatrix as a novel dural substitute: Examination of the efficacy, safety and outcome: Clinical experience on a series of 208 patients

Objectives Dural replacement materials and other measures can provide an effective barrier between the subarachnoid compartment and the extradural space when a watertight closure of the patient's own dura is not possible. Patients and methods We evaluated the efficacy and safety of a novel collagen-derived dural substitute on a series of 208 patients undergoing a variety of neurosurgical procedures. Results No patients experienced any local or systemic complications nor toxicity related to the dural patch. No patients experienced post-operative CSF fistula except for one. Post-operative MRIs showed signs of moderate inflammatory response in only one patient, who did not present any post-operative clinical symptom nor neurological deficits. Three patients underwent reoperation for bone flap repositioning after decompressive craniectomy: in these cases, the dural substitute appeared to have promoted a satisfactory dural regeneration, as confirmed by the histological studies. Furthermore, in such cases no or minimal adherences with the other tissues and the brain cortex was observed. Conclusions The new collagen-only biomatrix is a safe and effective dural substitute for routine neurosurgical procedures. The absence of local and systemic toxicity or complications, and the scarce promotion of adherences and inflammation, make this material appealing for its use as dural substitute even in cases when a needed re-operation is anticipated.

A new collagen biomatrix of equine origin versus a cadaveric dura graft for the repair of dural defects – a comparative animal experimental study

Numerous types of materials have been evaluated over the past decades in the quest for the ideal dural replacement, but no product fully meets all the applicable criteria. This paper presents the long-term results of an animal trial of a collagen biomatrix (TISSUDURA, Baxter AG, Vienna/Austria) for the repair and regeneration of dural defects. This product provides a matrix with a special layer structure and consists of pure naturally cross-linked collagen of equine origin. The comparable material is Tutoplast Dura, a human cadaveric-derived dural graft preserved in a multiple stage chemical process. Bihemispheric parietotoccipital dural defects of a defined size were induced in 25 sheep and subsequently closed with the collagen graft or Tutoplast Dura, respectively. Postoperative neurological abnormalities did not occur in any animal. There were no signs of graft rejection or formation of cerebrospinal fluid fistulae. The collagen graft site displayed histological signs as early as 2 weeks postoperatively consistent with a moderate Iymphocytic inflammatory response and infiltration with fibroblasts and macrophages. The graft subsequently developed a neodura-like connective tissue architecture. The Tutoplast Dura showed only minimal cellular infiltration, and again the surrounding structures displayed a mild inflammatory response. 24 weeks postoperatively, the dura and neomembrane were barely distinguishable at the collagen biomatrix site, but the Tutoplast Dura displayed inadequate fusion with the dural border and was encapsulated in a connective tissue layer. The outcomes demonstrate that the collagen graft can be used for dura reconstruction as a temporary dural replacement and at the same time as a biomatrix for dural regeneration.

The scalp flap only onlay: a method for managing large dural defects.

The standard approach to loss of substantial amounts of calvarium and dura is replacement of the dura with pathches, usually of biologic material such as fascia. We question the need for such patches and offer experimental and clinical evidence to support a different approach. Treatment of large calvarium and dural defects in 20 rats divided in two groups showed no difference in dural regeneration between animals repaired with patches and those repaired with the scalp flap only onlay on the brain. An illustrative clinical case confirms the observations. The scalp flap only onlay repair of cranial defects involving the dura provides a reasonable means for reconstruction. (1) In experimental animals there appeared to be no histologic difference between dura repaired by autogenous patch and that repaired by the scalp flap only onlay. (2) Clinically, well-nourished galea effects an ideal onlay repair of the dura. Secondary reconstruction of the bony calvarium can be performed utilizing a modified crane technique. (3) The procedure is simple in design, requires no donor sites, and certainly has application in cases other than trauma.

Dural replacement with resorbable collagen.

DEFECTS in the dura mater can result from craniocerebral trauma, neoplastic or inflammatory destruction, surgical removal, and congenital absence. The experimental work of Trotter, 1 Sayad and Harvey, 2 Cone, 3 Penfield, 4 and Keener, 5 indicates that if these dural defects are adjacent to soft tissue, adequate dural regeneration can occur in several weeks. Fibroblasts derived from surrounding mesenchymal tissue move into the defect restoring the continuity of the dura. However, if the defect is adjacent to bone, poor dural regeneration results, since the mesenchymal source for fibroblasts is not readily available. The advantages of closing such a dural defect are multiple. Closure prevents cerebral herniation with subsequent cerebritis, cerebrospinal fluid fistula with ensuing meningitis, and corticomeningeal adhesions with a resultant seizure focus. Materials used for the closure of dural defects have been reviewed by Pudenz, 6 Keener, 7 Teng, 8 and Rosomoff. 9 Replacement materials which have appeared

Chronic implantation of multiple macroelectrodes. A technique for mapping auditory neocortex in unanesthetized cats

A method is described for chronic implantation of electrodes which insures the contact between electrode tips and cortical surface during and after the period of dural regeneration. Results are presented that show similar tonotopic localization of the positive component of the evoked response in anesthetized and non-anesthetized cats.

The use of a sterile rubber glove as a covering for the dural defect resulting from the removal of a spinal cord tumor: Case report

1. 1. An operation is described during the course of which a large area of dura had to be sacrificed to facilitate the removal of a large, double dumb-bell type of spinal cord tumor. This dura was replaced with rubber from the back of a sterile rubber glove and the patient had an uneventful convalescence with no evidence of inflammatory reaction. 2. 2. The method of repair of dural defects described was suggested by the original work of Giangrasso, 1 who covered dural defects in animals with rubber from discarded gloves and who found that dural regeneration was rapid and that restoration of dural continuity was achieved without the formation of adhesions. 3. 3. This method may be of particular value in the armed forces where Cargile membrane or other animal membranes are difficult to obtain.