Decellularized small intestine submucosa device for temporomandibular joint meniscus repair: Acute timepoint safety study

Abstract

Temporomandibular joint (TMJ) Meniscus removal is an option for the patient to regain full range of motion if the disc is irreversibly damaged or unable to be reduced. However, this procedure leaves the joint vulnerable to condylar remodeling and degeneration. We have shown that extracellular matrix (ECM) scaffolds remodel into a tissue with near native TMJ meniscus in previous studies. The next step towards clinical translation is to manufacture the ECM scaffold as a device under good manufacturing practices (GMP) and test it in a pre-clinical animal study under good laboratory practices (GLP). The primary objective of this study was to evaluate the in-vivo histopathological response to a Prototype GMP manufactured device made of decellularized porcine small intestinal submucosa (SIS), by observing for signs of surrounding tissue reaction to the device that are indicative of an adverse host response in comparison to an empty control at 21 days post-surgical implantation in a canine TMJ meniscus removal and implant model in a GLP setting. The conclusive findings were that the ECM device is safe for placement in the TMJ. After 21 days post implantation, histology of tissue surrounding the device and draining lymph nodes showed that the Prototype GMP device had no negative effects compared to the empty site (as evaluated by the board-certified veterinary pathologist). Furthermore, there was a lack of negative findings for clinical pathology (hematology and clinical chemistry), mortality, and body weight/weight change. Future studies will go to one year after implantation to show that the remodel device remains as a viable tissue with near native mechanical properties.

Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies

“…Natural material derived scaffolds have the advantage of enabling cellular adhesion, growth factor encapsulation, enhanced cell proliferation and biochemical synthesis. The major natural scaffolding materials that have been used for meniscal tissue engineering are collagen and its composites [33,[216][217][218][219][220][221][222][223][224], hyaluronic acid (HA) [225][226][227][228][229][230][231], agarose [212,229,232,233], dECM from various tissues [57,61,122,[234][235][236][237][238][239][240][241][242][243][244], gelatin and its derivatives [208,212,[245][246][247][248][249][250] and silk fibroin [9,17,54,55,195,208,…”

The application of small intestinal submucosa in tissue regeneration

“…William L. Chung et al implanted the SIS stent in a model of the canine temporomandibular joint for medical removal and implantation. After 21 days, the histological tissue surrounding the device and draining lymph nodes displayed no adverse effects on the stent [ 125 ]. The SIS-derived ECM scaffold was utilized as a regenerative template for the TMJ disc in a pig model.…”

Enhancing cartilage regeneration and repair through bioactive and biomechanical modification of 3D acellular dermal matrix

“…Cell attachment and growth are critical for cartilage repair, and the support and bioactive factors provided by the submucosa promote favorable cell adhesion and growth on the scaffold. (iii) SIS exhibits good immunocompatibility and biocompatibility, thus minimizing the risk of immune rejection when implanted in the body [ 27 ]. Calcium sulfate hemihydrate (CSH) is commonly employed in cartilage tissue engineering to improve the biomechanical properties of scaffolds, owing to the following reasons: (i) the incorporation of CSH enhances the mechanical strength of the scaffold, preventing collapse or loss of shape of the cartilage tissue.…”