Gentrix® Surgical Matrix (3-layer) is intended for implantation to reinforce soft tissue where weakness exists in patients requiring urological, gastroenterological, or plastic & reconstructive surgery. Reinforcement of soft tissue within urological, gastroenterological, and plastic & reconstructive surgery includes, but is not limited to, the following open or laparoscopic procedures: hernia and body wall repair, colon and rectal prolapse repair, and esophageal repair. The Gentrix® Surgical Matrix (3-layer) minimizes tissue attachment to the device in case of direct contact with viscera.

Gentrix® Surgical Matrix and Gentrix® Surgical Matrix Hiatal (6-layer and 8-Layer) are intended for implantation to reinforce soft tissue where weakness exists in patients requiring gastroenterological or plastic & reconstructive surgery. Reinforcement of soft tissue within gastroenterological and plastic & reconstructive surgery includes, but is not limited to, the following open or laparoscopic procedures: hernia (e.g.: hiatal/diaphragmatic) and body wall repair, colon and rectal prolapse repair, tissue repair, and esophageal repair. The Gentrix® Surgical Matrix and Gentrix® Surgical Matrix Hiatal (6-layer and 8-Layer) minimizes tissue attachment to the device in case of direct contact with viscera.

Device Description

Gentrix Surgical Matrix and Gentrix® Surgical Matrix Hiatal device configurations are composed of porcine-derived extracellular matrix scaffically known as urinary bladder matrix ("UBM"). The implantable biomaterial is a resorbable extracellular matrix scaffold that provides mechanical reinforcement of soft tissue and will incorporate (remodel) into the body through cellular infiltration, capillary growth, and integration by the surrounding host tissue (as demonstrated in porcine models of ventral and hiatal hernia), while minimizing tissue attachment to the device in case of direct contact with viscera (as demonstrated in a preclinical rabbit cecal abrasion model). The devices are supplied in multiple layered sheet configurations in sizes up to 10 cm x 15 cm, and are available in rectangular and u-shape variations. All device configurations are packaged in double peel-open sterile barrier system. The devices are terminally sterilized using electron beam irradiation. The devices are intended for one time use.

AI/ML Overview

The document describes the Gentrix Surgical Matrix and Gentrix Surgical Matrix Hiatal devices. The acceptance criteria and the study that proves the device meets the acceptance criteria are primarily focused on demonstrating substantial equivalence to a predicate device and supporting the expanded indications for use.

Here's an analysis of the provided information based on your requested points:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a quantitative, pre-defined manner typical for AI/ML device performance. Instead, it describes studies conducted to support the substantial equivalence and safety/effectiveness of the device for its intended use, particularly for new indications like laparoscopic use and specific hiatal/diaphragmatic hernia repair, and minimizing tissue attachment.

The closest to acceptance criteria and performance can be inferred from the animal studies on tissue attachment:

Acceptance Criteria (Inferred from goals)	Reported Device Performance
Minimize tissue attachment compared to collagen mesh control in case of direct contact with viscera.	Day 14: Gentrix Surgical Matrix (3, 6, 8-Layer): 0% animals with attachments, 0 average attachment severity score, 0 total attachments, 0 cm average estimated attachment diameter, 0% device covered with attachments. Collagen Mesh Control: 17% animals with attachments, 0.2 average attachment severity score, 1 total attachment, 1.0 cm average estimated attachment diameter, 0.83% device covered with attachments.
	Day 90: Gentrix Surgical Matrix (3-Layer): 17% animals with attachments, 0.3 average attachment severity score, 1 total attachment, 1 cm average estimated attachment diameter, 4.17% device covered with attachments. Gentrix Surgical Matrix (6-Layer): 33% animals with attachments, 0.7 average attachment severity score, 3 total attachments, 0.5 cm average estimated attachment diameter, 0.83% device covered with attachments. Gentrix Surgical Matrix (8-Layer): 0% animals with attachments, 0 average attachment severity score, 0 total attachments, 0 cm average estimated attachment diameter, 0% device covered with attachments. Collagen Mesh Control: 67% animals with attachments, 1.0 average attachment severity score, 5 total attachments, 1.6 cm average estimated attachment diameter, 14.16% device covered with attachments.
Acceptable tissue responses with no instances of herniation or esophageal erosion or trauma in hiatal hernia repair model.	Porcine Hiatal Hernia Model (U-Shape design): Demonstrated acceptable tissue responses, no herniation, no esophageal erosion or trauma.
No impact on product performance from pre-fabricated u-shape design.	Porcine Hiatal Hernia Model (U-Shape design): Concluded that the pre-fabricated u-shape did not impact product performance.
Remodeling through cellular infiltration, capillary growth, and integration by surrounding host tissue.	Histological analysis (porcine and rabbit models): Demonstrated that subject devices undergo remodeling through cellular infiltration, capillary growth, and integration.
Safety and performance for enclosed indications (including hiatal hernia repair based on clinical literature).	Clinical Literature Review: Six retrospective publications supported the safety and performance for hiatal hernia repair. Outcomes varied by study (e.g., radiographic recurrence rates from 22% down to 0%, post-operative complication rates). The conclusion was that the clinical data provides support for the indications.
Substantial equivalence to predicate device (Gentrix™ Surgical Matrix 2-Layer, 3-Layer, 6-Layer, 8-Layer (K162554)) in terms of intended use, technological characteristics, and safety/effectiveness for new labeled uses. This is the overarching "acceptance criterion" for a 510(k).	The studies (pre-clinical animal studies, clinical data from literature) were designed to demonstrate that the subject devices have the same intended use as the predicate and equivalent technological characteristics, supporting the safety and effectiveness for new labeled uses (like hiatal hernia repair). The FDA's clearance letter confirms this substantial equivalence was met.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Pre-clinical (Animal) Studies Data (Test Set):
- Porcine Hiatal Hernia Model (U-shape design): 10 pigs. Prospective. Provenance not specified but typically conducted in controlled laboratory settings.
- Porcine Hiatal Hernia Repair Model (laparoscopic and hiatal/diaphragmatic hernia indications): Number of animals not explicitly stated, but it conducted over a 60-day study duration. Prospective. Provenance not specified.
- New Zealand White Rabbit Cecal Abrasion Model (tissue attachment): 6 animals per group (Control, GSM 3-Layer, GSM 6-Layer, GSM 8-Layer, Collagen Mesh Control) for Day 14 and Day 90. Total of 30 animals for each time point evaluation (assuming distinct animals for each time point or repeat measurements on same). Prospective. Provenance not specified.
Clinical Data (Test Set - from literature review):
- Retrospective Study 1 (Zografakis et al.): 62 patients. Retrospective. Provenance implied by the authors' affiliation if provided (not in this excerpt), likely US or Europe.
- Retrospective Study 2 (Howell et al.): 121 patients (56 UBM group, 65 non-UBM group). Retrospective. Provenance implied by the authors' affiliation if provided.
- Retrospective Study 3 (Sasse et al.): 15 patients. Retrospective. Provenance implied by the authors' affiliation if provided.
- Retrospective Study 4 (Reznichenko): 1 single patient. Retrospective. Provenance implied by the authors' affiliation if provided.
- Retrospective Study 5 (Reznichenko): 11 patients (4 reinforced with GSM). Retrospective. Rural community hospital setting, likely US.
- Retrospective Study 6 (Wang, C.Q. et al.): 37 patients (22 reinforced with GSM, 15 non-reinforced). Retrospective. Poster presentation at a society meeting, likely US.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Pre-clinical Studies:
- Porcine Hiatal Hernia Model: An independent clinical pathologist evaluated tissue morphology/health, considered "not clinically significant" the mild narrowing. Specific number of pathologists and their qualifications not stated, but "independent" implies objectivity.
- Rabbit Cecal Abrasion Model & Porcine Hiatal Hernia Repair Model: The evaluation of attachments, herniation, erosion, trauma, and histological analysis would have been performed by trained personnel (e.g., veterinarians, pathologists). Specific numbers and qualifications are not detailed.
Clinical Data (from literature):
- The "ground truth" here is the clinical outcomes reported by the original study authors (surgeons, researchers).
- Study 1: Single surgeon performing LHR.
- Study 2: 3 surgeons performing PHH repair.
- Study 3: Single surgeon performing LHR.
- Study 4: Single retrospective case.
- Study 5: Single surgeon performing LHR.
- Study 6: Same surgeon performing PHH repair.
- Qualifications of these surgeons are not provided in this summary, but they are implicitly qualified clinicians performing surgical procedures and assessing outcomes.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Pre-clinical Studies: The document does not describe a formal multi-expert adjudication method (like 2+1 or 3+1). Decisions appear to be made by individual evaluators (e.g., "independent clinical pathologist").
Clinical Data (from literature): Since these are summaries of published clinical studies, specific adjudication methods for their outcomes (e.g., recurrence, complications) were part of the original study designs. The summaries provided here do not detail such methods. Decisions on complications and recurrences were likely made by the treating physicians or study investigators.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

There is no mention of an AI/ML device in this document. Therefore, no MRMC comparative effectiveness study involving AI assistance for human readers was conducted or reported. This application is for a surgical mesh device, not an AI diagnostic tool.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Applicable to AI/ML devices only. As stated above, this is not an AI/ML device, so no standalone algorithm performance was assessed.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Pre-clinical (Animal) Studies:
- Pathology: Macroscopic and microscopic histological analysis of tissues to assess remodeling, inflammation, and integration.
- Direct Observation/Measurement: Assessment of herniation, esophageal erosion/trauma, and quantitative measurements of tissue attachments (percentage coverage, diameter, severity score), based on expert observation.
Clinical Data (from literature):
- Clinical Outcomes Data: Patient symptoms (shortness of breath, nausea, dysphagia, reflux), intraoperative/postoperative complications, reoperations, radiographic recurrence rates (contrast upper gastrointestinal series), endoscopic evaluations, BMI, HRQL scores, hospital length of stay, 30-day readmissions. These are derived from clinical practice and reported by the treating physicians/researchers.

8. The sample size for the training set

This is not an AI/ML device, so there is no concept of a "training set" in the context of machine learning model development. The document describes pre-clinical (animal) studies and a review of existing clinical data to support the safety and effectiveness of the device.

9. How the ground truth for the training set was established

Not applicable, as this is not an AI/ML device and there is no training set mentioned.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION".

February 7, 2019

ACell, Inc. Ms. Andrea Artman Sr. Regulatory Affairs Manager 6640 Eli Whitney Drive Suite 200 Columbia, Maryland 21046

Re: K182259

Trade/Device Name: Gentrix Surgical Matrix, Gentrix Surgical Matrix Hiatal Regulation Number: 21 CFR 878.3300 Regulation Name: Surgical Mesh Regulatory Class: Class II Product Code: FTM, OXH, OWV Dated: January 25, 2019 Received: January 28, 2019

Dear Ms. Artman:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and

Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Cynthia Chang -S

for

Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K182259

Device Name

Gentrix® Surgical Matrix (3-Layer, 6-Layer, and 8-Layer) Gentrix® Surgical Matrix Hiatal (6-Layer and 8-Layer)

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY Gentrix® Surgical Matrix Gentrix® Surgical Matrix Hiatal

Submitter:	ACell, Inc.
	6640 Eli Whitney Drive
	Columbia, MD 21046
Contact Person:	Andrea Pilon Artman
Contact Title:	Associate Director, Regulatory Affairs
Phone:	410-953-8549
Facsimile:	410-715-4511
Date Prepared:	January 15, 2019
Trade Name:	Gentrix® Surgical Matrix, Gentrix® Surgical Matrix Hiatal
Common Name:	Animal-Derived, Extracellular Matrix Surgical Product
Classification Name:	Mesh, Surgical, Collagen, Plastic and Reconstructive Surgery
Regulation Number:	21 C.F.R. § 878.3300
Regulatory Class:	Class II
FDA Product Code:	FTM, OXH, OWV

Predicate Device: Gentrix® Surgical Matrix 2-Layer, 6- Layer, 8-Layer (K162554) Reference Devices: The SURGISLS® Biodesign Tissue Graft (K073391, Cook Biotech Inc.) Biodesign® Diaphragmatic Hernia Graft (K133011, Cook Biotech Inc.)

Device Description

Intended Use/Indications for Use

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reconstructive surgery includes, but is not limited to, the following open or laparoscopic procedures: hernia and body wall repair, colon and rectal prolapse repair, tissue repair, and esophageal repair. The Gentrix® Surgical Matrix (3-layer) minimizes tissue attachment to the device in case of direct contact with viscera.

Summary of Technological Characteristics and Applicable Performance Data: The addition the Gentrix Surgical Matrix Hiatal device configuration, including the u-shape design, is supported by pre-clinical and clinical evidence. The u-shape design was studied in a pre-clinical porcine hiatal hernia model. A total of ten (10) pigs were used in this hiatal hernia model. Animals were randomly assigned to the reinforcement group or control group. The animals were survived for 60 days. Laparoscopic surgeries were successfully completed in all 10 animals. There was no noted damage or insult to the GSMH U-Shape device for any animal. All animals recovered from the surgery and there were no adverse events seen during the in-life portion of the study. Just prior to necropsy, endoscopic evaluation revealed mild narrowing at the distal end of the esophagus in all animals (non-reinforced control and reinforced). As all animals gained weight over the study with no evidence of GI complications, this narrowing was considered a result of the surgical procedure, rather than from the device, and was not considered clinically significant by the independent clinical pathologist.

The results demonstrated acceptable tissue responses with no instances of herniation or esophageal erosion or trauma, and concluded that the pre-fabricated u-shape did not impact product performance. In addition, data from clinical publications summarized below provided support for the addition of the new Gentrix® Surgical Matrix Hiatal configuration (u-shape) to the product line. No mechanical or biocompatibility testing were completed in support of this clearance as Gentrix Surgical Matrix is acting as its own predicate device. A table comparing the key features of the subject and predicate device is provided below.

Summary of Applicable Performance Data - Indications: Bench testing and pre-clinical animal testing was conducted to support the addition of laparoscopic use, minimized tissue attachment compared to the collagen mesh control, and specific hiatal / diaphragmatic hernia to the previously cleared indications for use statement. The laparoscopic and specific hiatal / diaphragmatic hernia indications were studied in a porcine hiatal hernia repair model; results demonstrated acceptable tissue responses with no instances of herniation or esophageal erosion or trauma over the 60- day study duration.

The formation of tissue attachments was evaluated in a New Zealand white rabbit cecal abrasion model; the results, presented in the tables below, demonstrated substantially equivalent tissue attachment to the device compared to the collagen mesh control in case of direct contact with viscera.

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	Day 14
Group	% Animals withAttachments(n = 6 animals / group)	AverageAttachmentSeverity Score *	Total #Attachments	Average EstimatedAttachmentDiameter	Average % DeviceCovered withAttachments
Control(No reinforcement)†	50% (3 of 6)	$1.0 \pm 1.1$	5	1.4 cm	N/A
Gentrix Surgical Matrix3-Layer	0% (0 of 6)	$0.0 \pm 0.0$	0	0 cm	0%
Gentrix Surgical Matrix6-Layer	0% (0 of 6)	$0.0 \pm 0.0$	0	0 cm	0%
Gentrix Surgical Matrix8-Layer	0% (0 of 6)	$0.0 \pm 0.0$	0	0 cm	0%
Collagen Mesh Control	17% (1 of 6)	$0.2 \pm 0.4$	1	1.0 cm	0.83%

	Day 90
Group	% Animals withAttachments(n = 6 animals / group)	AverageAttachmentSeverity Score *	Total #Attachments	Average EstimatedAttachmentDiameter	Average % DeviceCovered withAttachments
Control(No reinforcement)†	33% (2 of 6)	$0.7 \pm 1.0$	3	2.75 cm	N/A
Gentrix Surgical Matrix3-Layer	17% (1 of 6)	$0.3 \pm 0.8$	1	1 cm	4.17%
Gentrix Surgical Matrix6-Layer	33% (2 of 6)	$0.7 \pm 1.0$	3	0.5 cm	0.83%
Gentrix Surgical Matrix8-Layer	0% (0 of 6)	$0.0 \pm 0.0$	0	0 cm	0%
Collagen Mesh Control	67% (4 of 6)	$1.0 \pm 1.1$	5	1.6 cm	14.16%

The attachment severity scoring is a method that assesses the tenacity with which tissues are adhered. The highest average reported score in this model was a score of 1, which describes an easily detachable tissues can be safely separated from the study site with minimal use of blunt surgical tools.

7 The control (no reinforcement) group is a cohort of animals that underwent the same surgical procedure, but no device was placed at the site of the abrasion.

Histological analysis completed in the porcine and rabbit models demonstrated that the subject devices undergo remodeling through cellular infiltration, capillary growth, and integration by the surrounding host tissue. In addition, data from various published clinical and pre-clinical animal studies provided further support for the addition of the laparoscopic use, minimal tissue attachment, and specific hiatal / diaphragmatic hernia indications.

Summary of Clinical Data: There were no premarket clinical trials conducted to support the substantial equivalence of the subject devices. However, six (6) separate retrospective publications from the clinical setting were included in this submission, demonstrating the safety and performance of the subject devices for the enclosed indications.

Six (6) publications were identified for the hiatal hernia indication based on specific search criteria that was limited to English language publications with data was the same as the labeled indications for the Gentrix Surgical Matrix. The search was unlimited as to the type of clinical research (e.g. randomized trials, treatment studies, case reports included). Four of the six submitted clinical references (2, 4-6) utilized an anatomic classification system for defining the etiology of hiatal hernias (Types I-IV), as defined by the Society of American Gastrointestinal and Endoscopic Surgeons. The remaining two publications

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described the defect sizes of the hiatus. All surgeons evaluated patient symptoms when assessing the severity of a hiatal hernia and the need for surgical intervention, such as shortness of breath, nausea, dysphagia, and severe reflux. A detailed summary of the published clinical data is provided below.

1. Retrospective single-surgeon study of 62 patients who underwent Laparoscopic Hiatal Hernia Repair with diaphragmatic reinforcement using GSM 6-Layer'. All patients had a defect size of greater than 4 cm. The severity of the defects was not defined. A primary hiatal hernia repair with either a fundoplication or concomitant bariatric procedure (Rouxen-Y gastric bypass, laparoscopic sleeve gastrectomy, or gastrojejunostomy anastomosis revision) was performed for all patients.

Patient Demographics
Sample Size	Mean Age	Age Range	Mean BMI
Total 62F: 53 / M: 9	62 years	32–83 years	$32.7 kg/m^2$

No intraoperative complications were noted. The follow up was conducted for all patients at a minimum of 3 months at which time patients underwent a contrast upper gastrointestinal series. Postoperatively, successful endoscopic balloon dilation for dysphagia was conducted on 3 patients with no re-operative intervention. A radiographic recurrence rate of 22% (9/41) was identified during 3 month follow up; one (2.4%) became symptomatic and required operative revision 22 months after initial operative intervention.

1. A retrospective review of 121 patients who underwent isolated paraesophageal hiatal hernia (PHH) repair by 3 surgeons was performed . Fifty-six (56, 46.3%) were reinforced with Urinary Bladder Matrix (UBM) and sixty-five (65, 53.7%) were not reinforced. The decision of whether to use UBM was left to the surgeon. Patients in the UBM group had large defects or crural fibers attenuated. The size or severity of each defect was not defined. Fundoplication and cruroplasty reinforced with the use of Gentrix Surgical Matrix were compared to fundoplication and suture cruroplasty alone. Cases were performed robotically or laparoscopically with no conversions to open.
  There were 17 postoperative complications that occurred within 30 days of the procedure: 11 in the UBM group and 6 in the non-UBM group. The postoperative complications were graded according to Clavien-Dindo classification in the UBM versus non-UBM groups. Grade I complications included postoperative hypoxemia requiring new home oxygen, narcotic-induced lethargy, delayed gastric emptying that resolved with bowel rest, 2 selflimiting small pneumothoraces, and 3 failed trial of urinary voiding requiring Foley catheter reinsertion. Grade II complications included 1 new-onset atrial fibrillation and 1 deep vein thrombosis, both requiring anticoagulation. Grade IIIa complications included 1 case of bilateral pleural effusion requiring thoracentesis and 4 cases of dysphagia requiring esophagogastroduodenoscopy (EGD). The authors believe that only 2 of the complications

1 Zografakis et al. "Urinary Bladder Matrix Reinforcement for Laparoscopic Hiatal Hernia Repair". JSLS: Journal of the Society of Laparoendoscopic Surgeons. 22.2 (2018) 1-4.

2 Howell et al. "Paraesophageal Hiatal Hernia Repair With Urinary Bladder Matrix Graft". JSLS: Journal of the Society of Laparoendoscopic Surgeons. 22.2 (2018) 1-6.

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in the UBM group (dysphagia requiring EGD and dilation) could be deemed as meshrelated. There were no reports of reoperation. The results of the study demonstrate that there is no significant difference in post-operative complications, hospital length of stay, or 30-day readmissions between reinforced and non-reinforced patients.

Patient Demographics
	Sample Size	Mean Age	Age Range	Mean BMI	BMI Range
Total	56 (GSM)65(non-GSM)
Female	40(GSM)42 (non-GSM)	63.9 (GSM)54.3(non-GSM)	29–91 (GSM)20-88 (non-GSM)	29.6 (GSM)28.5 (non-GSM)	19–42 (GSM)17.7-45 (non-GSM)
Male	16 (GSM)23 (non-GSM)

1. A retrospective clinical review includes 15 laparoscopic cases of hiatal hernia repair with primary crural repair with GSM 3-Layer reinforcement and fundoplication'. The defects were an average of 6 cm in diameter. The severity of each defect was not defined. There was an average follow up period of 3 years where follow up was conducted via upper gastrointestinal (GI) series, endoscopy, and assessments of subjective symptoms of gastroesophageal reflux disease (GERD).

Patient Demographics
Sample Size	Mean Age	Age Range	Mean BMI	BMI Range
Total 15F: 9 / M: 6	53	27 - 72	34	22 - 59

Each repair was successfully completed laparoscopically, through a 12 mm trocar without noted damage. One patient underwent endoscopic balloon dilation for post-operative dysphagia that resolved without further intervention. No other complications occurred. The GERD-health-related quality of life (HRQL) scores averaged 6 (range, 0-12, of a possible 50), indicating little reflux symptomatology. Nine of the fifteen cases completed a follow-up upper GI series; all 9 showed intact repairs. An upper endoscopy was performed in 8 patients and showed no recurrences. There were no recurrences or long- term complications, such as erosion, strictures, or infections.

Retrospective case results of a single fifty three years old female patient that underwent 4. laparoscopic repair of a Type IV. 6 cm hiatal hernia defect with diaphragmatic crura reinforcement using GSM 6-Layer . There were no intra operative and peri operative complications. An upper gastrointestinal (UGI) series was conducted at 6 months and there was additional follow up at 24months. The study reported a normal Upper gastrointestinal (UGI) series at a 6 month follow-up visit. In addition, the patient did not have clinical recurrence of the hernia during the 24 months follow-up period.
Sasse, et al. "Hiatal Hernia Repair with Novel Biological Graft Reinforcement." JSLS: Journal of the Society of Laparoendoscopic Surgeons 20.2 (2016).

4 Reznichenko "Extracellular Matrix Scaffold in Diaphragmatic Crura Reinforcement During Lapair of Large Hiatal Hernia." Journal of Surgery and Transplantation Science 4(1) (2016): 1018.

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1. A Retrospective clinical review includes 11 patients who underwent laparoscopic repair of large hiatal hernias in a rural community hospital by a single surgeon . All hernias were primary, there were no revisional surgeries. Fundoplication performed in ten out of eleven patients, using anterior Dor technique in eight patients, Nissen in one patient, and Toupet in one patient. Four of the eleven patients were reinforced with GSM. Of the 11 hernias there was one (1) type II hernia defect (non-GSM), eight (8) type III hernia defects (3 GSM, 5 non-GSM), and two (2) Type IV hernia defects (1 GSM: 1 non-GSM). All hernia defects were greater than 6cm with at least 40% of the stomach in the chest. A standard laparoscopic hiatal hernia repair was performed using different biologically-derived grafts for crural reinforcement.

Patient Demographics
Sample Size	Mean Age	Age Range	Mean BMI	BMI Range	Avg. Defect Size
Total 11F: 6 / M: 5	$55.4 \pm 8.7$	42 - 68	$32.5 \pm 7.5$	22 - 46	All: 7.7 cm x 6.4 cmUBM: 8 cm x 6.75 cm

Follow-up was conducted at 6-24 months. During follow-up, 7 patients (64%) underwent radiological evaluation 2 patients (18%) underwent esophagogastroscopy. Of the four patients that were reinforced GSM, one patient had shortness of breath that was resolved. There were no other early or late complications experienced with the four cases reinforced with GSM.

1. A Retrospective clinical review of 37 patients who underwent paraesophageal hiatal hernia repair by the same surgeon . Of the 37 patients, 22 patients were reinforced with GSM 6-Layer over the crural repair and 15 patients did not receive reinforcement of the repair. Although Type I defects were excluded from this retrospective review, the size and severity of the defects were not defined. Patients returned for a one time follow up visit at a minimum of 12 months to assess for hernia recurrence both based on symptoms and radiographic evidence.

Patient Demographics
	Sample Size	Mean Age	Age Range
Total	Female14(GSM)11 (non-GSM)	$69.8 \pm 8.5$ (GSM)	50-87 (GSM)
	Male8 (GSM)4 (non-GSM)	$68.7 \pm 9.9$ (non-GSM)	48-83 (non-GSM)
	22 (GSM)15 (non-GSM)

Recurrence occurred in 31.8% of patients in the GSM group and 46.7% non-reinforced group. Two GSM reinforced patients underwent re-operation due to recurrence. Secondary outcome measures were assessed including post-operative complications and quality of life. The percentage of patients that demonstrated radiographic evidence of recurrence was less in the GSM reinforced group when compared to the non-reinforced group, though this and other measures were not statistically significant. There were no differences in complications between the GSM reinforced group and the non-reinforced group.

3 Reznichenko "Different Biologic Grafts for Diaphragmatic Crura Reinforcement During Laparoscopic Repair of Large Hiatal Hernia: A Six - Year Single Surgeon Experience." Journal of Current Surgery 6.1 (2016): 6-13.

" Wang, C.Q. et al. "Symptomatic, Radiographic, and Quality of Life Outcomes After Paraesophageal Hernia Repair with MatriStem Surgical Matrix" The Society for Surgery of the Alimentary Tract 58th Annual Meeting Poster Presentation. Chicago, IL.

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	ACell, Inc.Gentrix® Surgical MatrixGentrix® Surgical Matrix Hiatal	ACell, Inc.Gentrix™ Surgical Matrix 2-Layer,3- Layer, 6-Layer, 8-Layer
510(k) No.	TBD	K162554
Device Class	Class II	Class II
Product Code	FTM, OXH, OWV	FTM, OXH
Classification	ECM, Surgical Mesh	ECM, Surgical Mesh
Intended Use /Indications forUse	Gentrix® Surgical Matrix (3-layer) is intended forimplantation to reinforce soft tissue where weaknessexists in patients requiring urological,gastroenterological, or plastic & reconstructive surgery.Reinforcement of soft tissue within urological,gastroenterological, and plastic & reconstructive surgeryincludes, but is not limited to, the following open orlaparoscopic procedures: hernia and body wall repair,colon and rectal prolapse repair, tissue repair, andesophageal repair. The Gentrix® Surgical Matrix (3-layer) minimizes tissue attachment to the device in caseof direct contact with viscera.Gentrix® Surgical Matrix and Gentrix® Surgical MatrixHiatal (6-layer and 8-Layer) are intended forimplantation to reinforce soft tissue where weaknessexists in patients requiring gastroenterological or plastic& reconstructive surgery. Reinforcement of soft tissuewithin gastroenterological and plastic & reconstructivesurgery includes, but is not limited to, the following openor laparoscopic procedures: hernia (e.g.:hiatal/diaphragmatic) and body wall repair, colon andrectal prolapse repair, tissue repair, and esophagealrepair. The Gentrix® Surgical Matrix and Gentrix®Surgical Matrix Hiatal (6-layer and 8- Layer) minimizestissue attachment to the device in case of direct contactwith viscera.	Gentrix™ Surgical Matrix 2-layer and3- Layer are intended for implantation toreinforce soft tissue where weaknessexists in patients requiring urological,gastroenterological, or plastic &reconstructive surgery. Reinforcement ofsoft tissue within urological,gastroenterological, and plastic &reconstructive surgery includes, but isnot limited to, the following procedures:hernia and body wall repair, colon andrectal prolapse repair, tissue repair, andesophageal repair.Gentrix™ Surgical Matrix 6-layer and 8-Layer are intended for implantation toreinforce soft tissue where weaknessexists in patients requiringgastroenterological or plastic &reconstructive surgery. Reinforcement ofsoft tissue within gastroenterological andplastic & reconstructive surgery includes,but is not limited to, the followingprocedures: hernia and body wall repair,colon and rectal prolapse repair, tissuerepair, and esophageal repair.
Material Source	Porcine Urinary Bladder	Porcine Urinary Bladder
Material Type	Collagen, Extracellular Matrix	Collagen, Extracellular Matrix
Resorbable	Yes	Yes
Shape	Rectangular and U-Shape	Rectangular
Nominal Sizes	Up to 10 cm x 15 cm	Up to 10 cm x 15 cm
Reusable	Single Use Device	Single Use Device
Packaging	Dual Foil:PET Pouch System	Dual Foil:PET Pouch System
Sterilization	electron beam irradiation	electron beam irradiation

Conclusions

The Gentrix® Surgical Matrix and Gentrix® Surgical Matrix Hiatal device configurations have the same intended use as the predicate device, as demonstrated by the preclinical animal studies and clinical data from literature used to support the safety and effectiveness for the new labeled use of hiatal hernia repair. In addition, the subject device has the equivalent technological characteristics as the predicate device. Therefore, the Gentrix® Surgical Matrix and Gentrix® Surgical Matrix Hiatal device configurations are substantially equivalent to the cleared predicate devices.

Regulation Number and Section

§ 878.3300 Surgical mesh.

(a)
Identification. Surgical mesh is a metallic or polymeric screen intended to be implanted to reinforce soft tissue or bone where weakness exists. Examples of surgical mesh are metallic and polymeric mesh for hernia repair, and acetabular and cement restrictor mesh used during orthopedic surgery.(b)
Classification. Class II.