The primary goal of surgical management of perianal fistula (PF) is to eradicate any existing infection and promote definitive closure of the fistula tract without compromising the function of the sphincter complex. With current surgical management techniques, successful treatment of PFs remains a challenge due to high recurrence rates and the potential for injury to the sphincter complex, which can result in incontinence [1, 2]. This problem is compounded due to the number of PFs associated with inflammatory bowel disease, including Crohn's disease [3] and ulcerative colitis [4], which can result in complex fistulas that often require a multidisciplinary approach [5]. These challenges will continue to grow due to the chronic nature of these disease states and their increasing global prevalence [6]. However, perianal abscess remains the overwhelming contributing factor in the pathogenesis of PFs. Importantly, the incidence of the disease states may be underreported due to social stigma associated with the condition. This combination of factors presents a need for surgical advances in the management of PFs.
Currently, invasive surgical procedures such as ligation of inter-sphincteric fistula tract (LIFT) and mucosal advancement flaps, offer high clinical efficacy, but still carry a risk of post-operative complications, including infection, bleeding, or anal sphincter damage [7, 8]. Less invasive techniques, such as fibrin glue injection and traditional fistula plugs, minimize these complications but often result in poor closure rates and a high recurrence rate [9, 10]. More recently, surgical management advances have included techniques that incorporate video-assisted procedures in an attempt to limit incontinence associated with injury to the sphincter complex [11]. Similarly, ablative techniques have demonstrated success in mitigating sphincter damage but carry a high recurrence rate with moderate clinical efficacy [12, 13]. Stem cell therapies have also shown value, particularly with respect to fistulas related to Crohn’s disease, but future studies evaluating PFs of other etiologies are needed [14, 15].
Therefore, a need still exists for a minimally invasive, clinically effective, simple, and cost-effective alternative to traditional surgical interventions for PF. This has led many surgeons to explore regenerative biomaterials as a treatment option, such as biologic anal fistula plugs [16, 17]. Biological implant materials, in both allograft and xenograft form, have seen adoption in PF management [18, 19]. However, the goal of many fistula plugs is to provide a method of occluding the fistula alone without a specific focus on augmenting tissue regeneration. For this reason, biologic fistula plugs have demonstrated success in limiting incontinence and surgical complications but exhibit varying degrees of clinical efficacy. More recently, a biologic implant derived from ovine forestomach matrix (OFM) has been studied as a novel alternative to the traditional plugs with promising early success [20]. OFM is a decellularized extracellular matrix (dECM) that preserves inherent tissue architecture and retains biomolecules crucial to the tissue regeneration process [21]. In this study by Hsu et al, 14 patients received OFM as a perianal fistula implant (PAFI) and were followed for a median 37.6 ± 20.1 weeks. Of the 78.6% (n = 11/14) of patients that healed during the study, median time to complete closure was 3.6 weeks. Only two patients in the study required an additional OFM PFAI procedure and no adverse events or post-operative infections were reported.
In addition to its preliminary success as a PAFI, OFM may serve as an ideal implant device due to its ability to function in an inflammatory and contaminated environment. OFM devices have been show to modulate wound proteases in preclinical [22] and clinical studies [23] and may be particularly effective in the inflammatory environment present in PFs. Additionally, OFM has demonstrated the ability to recruit mesenchymal stromal cells [24], stimulate cell proliferation and angiogenesis [25], all of which are key components of tissue regeneration. OFM has been further employed in the regeneration of multiple types of contaminated soft tissue defects, in addition to the recent use as a PAFI [20, 26–29]. The combination of initial clinical efficacy in PFs and in other contaminated, inflammatory tissues has led the authors to perform a larger single-center, retrospective case series to validate the previously published PAFI pilot study in a new, larger patient population. OFM was evaluated as a PAFI to facilitate closure, minimize post-operative complications, and negate the need for more invasive surgical interventions.