Evolution of synthetic graft materials and dural sealants for cerebrospinal fluid leak repair

Introduction

Numerous methods have been developed over the years to assist in providing optimal outcomes and minimize postoperative cerebrospinal fluid leak (CSF) rates after skull base surgery. Especially inherent to the endoscopic approach is incision or resection of dura, which can vary from being only limited to the sella to involving more extensive dural surfaces (e.g., cribriform plate, planum sphenoidale, clivus). Although dependent on surgeon preference and skill, as well as the type of defect and extent of flow, repairs are commonly achieved with a combination of underlay (subdural, epidural, or both) and an overlay graft or flap, with intervening absorbable hemostatic agents (e.g., cellulose, gelatin foam) and, in certain cases, an absorbable glue or sealant as adjuncts. ^, The goal is to simulate a reliable dural substitute that can achieve a watertight closure to prevent egress of CSF, minimize intracranial infection, and provide a surface along which the wound can form neodura. Ultimately, most modern repairs consist of some combination of free autografts, vascularized flaps, synthetic dural replacement grafts, and synthetic absorbable sealants and glues.

Autologous versus synthetic grafts

Among the various graft materials available, autologous grafts have remained a popular choice because of their high biocompatibility (no risk of rejection), pliability, low economic cost, and low risk of infections to the patient. However, procuring autologous tissue for grafting often requires creating a second surgical site, which increases the risk for secondary morbidities associated with another wound site (e.g., hematoma, seroma, infection). Graft harvesting also incurs additional preoperative planning as well as operative and anesthetic time. Moreover, hypoxia of the autologous graft can induce inflammatory reactions that can lead to the formation of adhesions. Additionally, autologous grafts, often necessitate being 25% larger than the defect because of their tendency to shrink in size by as much as 20%, depending on tissue type. ^, Many autologous grafts, such as abdominal fat or fascia lata, are harvested in a sterile manner, but others, such as nasal mucosa, are harvested directly from the nasal cavity, which is a clean-contaminated space.

On the other hand, synthetic materials have the advantage of being sterile and therefore free from human pathogens. Moreover, no surgical procedure is required to procure them, thereby avoiding donor site morbidity, and they can be readily manufactured in virtually unlimited quantities and in multitudes of shapes and sizes. Additionally, recent advancements in materials engineering have introduced new classes of synthetic graft materials, including acellular human dermis and engineered collagen matrix, that alleviate previous concerns of biocompatibility associated with xenografts and older generations of synthetic grafts (e.g., silicone, polytetrafluoroethylene [PTFE]). The lack of class II antigens enables these new synthetic grafts to circumvent previous issues with host rejection and graft failure. Additionally, their microstructure designs enable faster healing time by promoting fibroblast proliferation and blood vessel ingrowth and rapid incorporation into surrounding tissues. Nevertheless, acellular dermis remodeling by host fibroblasts and angiogenic factors have still been reported to be slower than that observed in autografts. Therefore, use of some synthetic materials may come at the cost of longer periods of postoperative crusting and an extended healing period. Moreover, although autologous tissue procurement incurs additional preoperative planning and additional operative and anesthetic time, synthetic materials can sometimes be more costly.

In light of these differences, both material types have shown promise in successful skull base reconstruction, with frequent use of combinations of both tissue types. A meta-analysis by Abiri et al. found that there was no significant difference in postoperative CSF leak outcomes between exclusive use of autologous versus synthetic grafts, which lends support to the idea that meticulous closure technique and enforcing postoperative precautions and protocols, as opposed to material type, is likely more important for successful skull base reconstruction.

Acellular human dermis

Over the past decade, acellular human dermis has gained in popularity in many areas of skull base surgery and has become increasingly more common in the reconstruction of skull base defects. In contrast to classical allografts and xenografts, acellular dermis is a cell-free biomaterial that possesses the molecular and structural features of dermal tissue. During its synthetic processing, all major histocompatibility complex antigens are removed to render the material immunologically inert. Additionally, the graft is terminally sterilized to ensure that it is clear of infectious bacteria and viruses. Acellular dermis grafts, such as AlloDerm (BioHorizons), are derived from the tissue of donated cadavers and therefore do not incur additional operative time for graft harvest as would be required for autologous grafts. However, a reconstitution process, typically involving about 10 minutes of soaking in lactated Ringer’s or normal saline solution, is required before in vivo use. This material benefits from its low tendency to shrink and its softness, pliability, and elasticity that facilitate graft maneuvering and placement. After it has been placed, the graft is able to retain its structural integrity as it gradually becomes repopulated and revascularized with the patient’s fibroblasts and endothelial and epithelial cells during neodura generation. Moreover, its acellular ultrastructure consisting of basement membrane components, including type IV and VIII collagen and laminin, has been theorized to facilitate epithelial adherence and reduce adhesion formation. ^, However, remodeling by host fibroblasts and angiogenic factors also carries the burden of significantly longer periods of postoperative crusting compared with mucosal grafts. Postoperative crusting in the nose can hinder mucosalization, obstruct the nasal airway and create significant sinonasal symptoms, and impede proper surveillance of the operative site. Therefore, use of acellular dermis grafts may entail regular in-office debridement of crusts during the postoperative recovery period to ensure adequate healing of the underlying tissue. Overall, recent studies have demonstrated acellular dermal matrices to perform as well as, if not better than, autologous grafts in skull base surgeries. In Gaynor et al.’s cohort of 160 patients with intraoperative CSF leaks during transsphenoidal pituitary surgery reconstruction, only 8.4% in the acellular dermis group versus 15.2% in the fat graft group experienced postoperative CSF leaks. Additionally, despite its higher cost, acellular dermal grafts may ultimately be less expensive than autologous materials because of the time saved in the operating room and postoperatively, with comparable outcomes.