Techniques in Orthopaedics® 22(1):43–54 © 2007 Lippincott Williams & Wilkins, Inc.

Biologics in Rotator Cuff Surgery: Management of Rotator Cuff Tears With an Extracellular Matrix Patch Matthew T. Provencher,

M.D.,*

Augustus Mazzocca,

M.D.,†

and Anthony A. Romeo,

M.D.*

Summary: Chronic large and massive rotator cuff tears remain a treatment challenge for the orthopaedic surgeon. The use of an extracellular matrix (ECM) biologic patch is an emerging field and offers potential for the treatment of patients with failed rotator cuff repairs or those with tears that are chronic and large in nature. There are several commercially available grafts that are derived from a variety of allogeneic (dermis) and xenogeneic (dermis and small intestinal submucosa) sources. An extensive amount of basic science and preclinical models have demonstrated that an ECM patch may offer improved healing rates with a biomechanical profile that nearly reproduces the characteristics of the native rotator cuff tendon. One should keep in mind the exact application of the ECM patch when interpreting studies, either as an augmentation (onlay) versus interpositional (intercalary) technique, which may significantly alter the overall efficacy of the ECM patch. Although there is an extensive amount of basic science and preclinical work to justify their use in animal models, the application of ECM patches in the human setting has not been as encouraging. The purposes of this paper are to review the basic science and preclinical data on the use of ECM patches, to describe current clinical indications, techniques, and to review the results in both animal and human studies. Key Words: Rotator cuff tear— Chronic—Failed rotator cuff repair—Massive—Extracellular matrix—Rotator cuff augmentation—Biologic augmentation—Graft substitute—Small intestinal submucosa— Human dermal matrix.

Chronic full thickness tears of the rotator cuff remain a treatment challenge for the orthopaedic surgeon. The overall healing capacity of a chronic rotator cuff tear is diminished because of poor tissue quality and compromised blood supply. In addition, the muscle-tendon units27,28 are frequently subjected to high amounts of stress that may preclude a reasonable tissue repair to the rotator cuff footprint of the humeral head. In addition, chronic rotator cuff tears are associated with muscle volume loss, fatty infiltrate, tendon retraction, scar tissue, delamination, and poor suture handling characteristics.24,27,58,65 These changes associated

with chronic large or massive rotator cuff tears have lead to a high rate of failure after primary surgical repair and a high rate of tendon rerupture.24 –28,30,50,51,58,65 Tissue augmentation has long been recognized for its potential ability to improve biomechanical stability and healing in a variety of tendon and ligament repairs.1,3,11,14,34 The technology and techniques of tissue engineering have improved to allow for application of tissue patches in the rotator cuff. There is considerable interest in tissue augmentation procedures, especially in chronic, retracted large, and massive tears in individuals who are not candidates for arthroplasty. Rotator cuff patches have the potential capacity to improve the healing environment, which is an attractive option given that an intact rotator cuff after repair has better functional outcomes.24 –26,30,65 In general, rotator cuff patches are composed of a collagenous matrix, which is derived from xenogeneic or allogeneic human tissues depending on manufacturer. The collagenous matrix is a scaffold that is comprised of several

From the *Department of Orthopaedic Surgery, Rush University, Division of Shoulder and Sports Surgery, Chicago, Illinois; †Department of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut. Address correspondence and reprint requests to Matthew T. Provencher, M.D., Department of Orthopaedic Surgery, Rush University, Division of Shoulder and Sports Surgery, 1725 West Harrison, Suite 1063, Chicago, IL 60612. E-mail: [email protected]

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types of purified collagen, primarily type I. The collagen may be cross-linked to improve strength18,22,33,35 and also reduce antigenicity.18 However, concerns with the use of processed collagen include the presence of donor DNA68 (animal or human), infection transmission, and inflammatory reactions. In addition, the longevity and breakdown characteristics of tissue patches in vivo vary widely and are not well studied. Although varieties of animal and biomechanical models have shown promise of rotator cuff patches, there remains a paucity of clinical evidence to support their routine use. However, some recent evidence may support their efficacy in very early follow-up studies. The benefits of an extracellular matrix (ECM) patch are compelling and include retention of the native 3-dimensional structure, with preservation of collagen, proteins, growth factors, and proteoglycans.1,4,8,9 –11,14,16,29,31,33,34,53,62,66,67 The purposes of this article are to review the currently available rotator cuff patches and describe the typical cellular responses and biomechanical data, as well as clinical results in both animal models and human use. In addition, current indications and techniques for surgical rotator cuff patch augmentation will be highlighted.

TYPES OF GRAFTS Rotator cuff patches are frequently referred to as ECM. An ECM is a complex structural entity that surrounds and supports mammalian cells and is the cell part of a tissue that is not part of any cell. The ECM is comprised of structural proteins (collagen), specialized proteins (fibrillin, fibronectin), and various proteoglycans. Rotator cuff ECM patches have been engineered to contain collagen as a scaffold from a variety of human and xenograft sources. Human sources include processed human dermal tissue, whereas animal sources include porcine small intestine submucosa (SIS), porcine dermis, and equine pericardium. Other graft sources have been described; however, the majority are derived from human dermis or porcine (Table 1). SIS ECM Patch SIS is available through several manufacturers, each with a proprietary processing and sterilization process. The CuffPatch Bioengineered Tissue Reinforcement manufactured by Organogenesis (Canton, MA), distributed by Arthrotek (Warsaw, IN) is acellular porcine SIS ob-

TABLE 1. Graft Sources Product Name

Manufacturer

Licensing/ Distributor

GraftJacket Regenerative Tissue Matrix

LifeCell (Branchburg, NJ)

Wright Medical Technology (Arlington, TX)

BioBlanket

Kensey Nash Corporation (Exton, PA) TEI Biosciences (Boston, MA) Tissue Science Laboratories (Aldershot, Hampshire, UK) Organogenesis (Canton, MA)

Not yet available

TissueMend

Zimmer Collagen Repair patch

CuffPatch Bioengineered Tissue Reinforcement Restore DePuy Orthobiologic Orthopaedics Implant (Warsaw, IN) OrthADAPT Pegasus Biologics (Irvine, CA)

Tissue Type

Source

Sizes

Thickness

Dermis

Human

5 ⫻ 5 cm; 5 ⫻ 10 cm, GraftJacket Extreme 4 ⫻ 7 cm

1.0 mm (Extreme 2.0 mm)

Cross-Linked/ Irradiated No/No

Other Information Hydration prior to use (10–15 min)

Yes/Gamma

Stryker (Mahwah, NJ)

Dermis

Bovine

5 ⫻ 6 cm

1.1 mm and No/No 1.2 mm

Hydrated less than 1 min

Zimmmer (Warsaw, IN)

Dermis

Porcine

5 ⫻ 10 cm

1.5 mm

Yes/Gamma (?)

Stored at room temperature; hydration not required

Arthrotek (Warsaw, IN)

SIS

Porcine

6.5 ⫻ 9 cm

0.6–1.0 mm

Yes/Gamma

Depuy Orthopaedics (Warsaw, IN) Pegasus Biologics

SIS

Porcine

63 mm diameter (circular)

1.0 mm

No/Electron beam

Packaged hydrated; hydration not required Hydration 5–10 min

3 ⫻ 3 cm up to 9 ⫻ 10 cm, strips also available

0.5 mm

Yes/No

SIS, small intestine submucosa. Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

Pericardium Equine

BIOLOGICS IN ROTATOR CUFF SURGERY tained by a nonenzymatic cleaning process. A total of 8 layers of collagen are cross-linked via lamination of the submucosal layers, and packaged in a hydrating solution. Another type of SIS patch called the Restore Orthobiologic Implant is manufactured by DePuy Orthopaedics (Warsaw, IN), which contains 10 layers of submucosa that are laminated together via a vacuum press. After chemical cleansing, each successive submucosal layer is oriented 20 degrees relative to the other, not cross-linked, and packaged dry. Porcine SIS has been one of the longest available xenografts for cuff tear augmentation. Dermal ECM Patches Xenograft dermal implants have received recent attention and several manufacturers have produced acellular sheets of animal derived collagen dermal tissue. TissueMend Soft Tissue Repair Matrix (TEI Biosciences, Boston, MA) distributed by Stryker Orthopaedics (Mahwah, NJ) is 1-layer of bovine dermis, which is packed dry after processing with lyophilization. The Zimmer Collagen Repair Patch (ZCR) (Tissue Science Laboratories, Aldershot, Hampshire, UK) is derived from porcine dermis, which is cross-linked after enzymatic cleansing. Human dermal tissue is the graft source for the GraftJacket Regenerative Tissue Matrix (LifeCell, Branchburg, NJ), distributed by Wright Medical Technology (Arlington, TN). Originally marketed for skin coverage in diabetic foot ulcers, the graft is processed with proprietary methods to remove epidermis and other dermal cells, leaving an acellular dermal layer through freeze-drying techniques, which claim to retain the proteins, collagenous structure, and vascular channels of the dermis. The manufacturer states that collagen types I, III, IV, and VII, as well as elastin, proteoglycans, and growth factors are retained because the product is not chemically cross-linked or terminally sterilized. The graft requires up to 15 minutes of hydration as it is packaged dry after a freeze-drying process. An equine pericardial patch, known as OrthADAPT (Pegasus Biologics, Irvine, CA) is currently available as an acellular collagenous matrix, which is cleansed, but not irradiated. CELLULAR RESPONSES OF BIOLOGIC ROTATOR CUFF PATCHES As with any implanted allograft or xenograft tissue, there is concern regarding the inflammatory reaction, tissue reorganization, safety, and host-tissue morphologic response. A large body of evidence has tested

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various ECMs in animal models to ascertain reactions on a cellular level to provide insight into eventual incorporation and healing of the patch. The exact cellular response is dependent on not only tissue of origin, but also processing techniques (many of which are proprietary), and host tissue testing medium.61 The use of ECM is also not restricted to orthopaedics. In fact, much of what is known about ECM patches is derived from other applications, including skin,4,48,57,62 vascular grafts,47 periosteum,14 bladder wall,34 and dural tears.16 The majority of initial work has focused on SIS; however, allogeneic and xenogeneic dermal graft sources have become popular. Processing Techniques on the Cellular Response The amount of acceptable inflammation after ECM implantation is unknown. Although some level of inflammation is part of the healing response,6 inert materials may be desirable augments. For example, chemical cross-linking during the processing of ECM diminishes the surface recognition of epitopes6,8 that may prevent degradation of the graft by a cellular response. The cross-linked tissue is coated with host fibrous tissue and exhibits a decreased inflammatory response, however, this is debatable. In contrast, those tissues without chemical cross-linking undergo tissue remodeling that is more pronounced than tissues that are cross-linked. In addition, it has been shown that noncross-linked tissues may have a protective response to resist bacterial contamination.7,12 Certain chemical cross-linking treatments have also been associated with increased end-product tissue calcification33 and toxicity. In general, chemical cross-linking also allows the tissue to be somewhat immunoprivileged, preventing recognition of surface epitopes and subsequently preventing degradation by the host environment.6 In contrast, ECM scaffolds that have not been cross-linked are subject to more rapid tissue degradation secondary to a more robust immune response. This includes rapid vascular recruitment (neovascularization), mononuclear cell infiltration, and tissue remodeling comprised of differentiated cell populations.6,61 The degradation products of nonchemically cross-linked ECM patches act as chemoattractants that assist with scaffold degradation. Some of these marrow-derived cells may play an important role in the healing of a rotator cuff tear with ECM augmentation, enhanced beyond what is normally recruited by a native healing tendon.6 The main concern with xenografting continues to be disease transmission and graft rejection. The ability to remove viral and other cell burdens from xenograft tissue has been studied6,7; however, disease transmission remains a small, but significant concern. To our knowlTechniques in Orthopaedics®, Vol. 22, No. 1, 2007

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edge, there have been no xenograft-associated diseasetransmission issues for ECM; however, xenograft wholeorgan donation is a different story. Surface epitopes expressed on xenogeneic cell membranes may undergo antibody recognition when transplanted into humans. However, even though epitopes have been identified in processed xenograft tissue, their relatively small density precludes the mounting of a complement-activated immune response.5,6 Synoviocytes have been theorized to play a role in the remodeling and repair of ECM patches. Noncross-linked collagen scaffolds coated with fibroblast-like synoviocytes (FLS)21 demonstrated better spatial distribution of FLS and better collagen production versus cross-linked versions. Tenocytes isolated from rabbit tendon have also been seeded onto ECM patches in an animal model, which has demonstrated improved rotator cuff healing response rates.63 ECM grafts augmented with FLS are not commercially available; however, the addition of certain engineered exogenous collagen reparative cells shows promise. Endothelial cell conditioning has also been investigated for the applicability in ECM,64 primarily as an improvement with in vivo tissue organization and increased metabolic activity, with lower amounts of inflammatory prostaglandin (PGI-2). Although the concurrent treatment of an ECM patch with mesenchymal stem cells is attractive, this application has not been well studied. In addition, the effects of irradiation on ECM tissue implantation are not well known. SIS (Xenogeneic Small Intestine Submucosal) Cellular Responses SIS is derived from xenogeneic jejunum tissue after removing several layers of the intestine (tunica mucosa, serosa, and muscularis) and has a relatively long history in animal and human clinical studies as a scaffold for tissue repair and remodeling. The heterogeneic nature of SIS is due to the differing areas of intestinal graft harvest (even within the jejunum itself) and may limit the reproducibility of graft homogeneity. Raghavan49 and colleagues investigated the variations in different harvest sites of porcine SIS (distal and proximal sections) and found that not all SIS harvests were the same; biomechanical properties of the SIS graft differed among sampling sites. For example, distal samples were more elastic and less permeable. The overall host response to an ECM varies depending on tissue processing and is different for those matrices that are chemically cross-linked and those that are not. In general, xenograft ECM grafts are chemically crossTechniques in Orthopaedics®, Vol. 22, No. 1, 2007

linked (usually glutaraldehyde or peracetic acid) to allow transplantation to humans, reduce epitope and other cell burden, and reduce antigenicity.6 However, even aggressive cross-linking mechanisms do not remove all of the antigenicity, cells, growth factors (especially VEGF),31 and porcine DNA68 with continued epitope recognition.42 In an SIS patch, there is a well documented temporal course of cellular responses, which is affected by tissue processing.61 In the early period (2 to 3 weeks), a vigorous host cellular response is noted, with a proliferation of mononuclear cells in the first 72 hours. Some studies have demonstrated that up to 80% to 90% of the ECM patch is removed by 4 weeks and is replaced by host tissues, however, multilaminate forms of SIS ECM may take up to 4 months for full integration.8 Marrow derived cells populate this area and are associated with areas of angiogenesis and inflammation.67 Thus, an SIS ECM has been shown to have the ability to recruit marrow-derived cells to the remodeling area. In the absence of SIS, marrow-derived cells are not present,67 however, this finding is debatable. Animal models have routinely shown good incorporation of SIS grafts with minimal immune response. In a Mongrel dog model, an SIS patch was used as an infraspinatus interpositional graft.19 By 3 months, the SIS tissue was well integrated into the humerus (endochondral ossification) and demonstrated fibrous interdigitation between the regenerated tissue and adjacent rotator cuff muscle,19 without evidence of an inflammatory response. By 6 months, the graft showed marked remodeling with an abundant collagenous matrix oriented with the long axis of the infraspinatus tendon. Others have shown similar results in animal models with neovascularization, a collagenous matrix, and well-oriented fibroblasts along the lines of stress, much like a native tendon.38,66 In a sheep infraspinatus rotator cuff repair patch augmentation model, Nicholson and colleagues45 found that by 9 weeks, the majority of SIS patches were completely resorbed, and a combination of fibroblasts and macrophages had invaded the area. Dermis (Allogeneic and Xenogeneic Derived) Cellular Responses Similar to SIS tissue, dermal xenogeneic and allogeneic tissues demonstrate rapid infiltration of fibroblasts, vascular tissue, with minimal host inflammatory response.2,14 However, others61 have shown that a dermal allograft tissue (GraftJacket) demonstrated a persistent low-grade inflammatory response with fibrous connective tissue at nearly 4 months in a rat model. Degradation products of ECM have been shown to have the potential

BIOLOGICS IN ROTATOR CUFF SURGERY to act as chemoattractants for endothelial cells, marrowderived cells, and fibroblasts.37 Adams et al.2 studied an allograft dermis implant (GraftJacket) in a canine model for full-thickness infraspinatus tears. At 6 weeks, chronic inflammation was consistent with surgery and repair. By 6 months, the bone-tendon interface contained Sharpey’s fibers, although 2 of the grafts showed discontinuity of the graft-humerus interface (20% failure rate), and a higher rate of inflammation. A robust, remodeled tendon-like structure that contained elastin was present. Inflammatory cells were present in all specimens, but were found to surround the suture material and were thought to represent a foreign body reaction.

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Comparison of SIS to Dermal Patches Commercially available ECMs demonstrate differences in the cellular response. The exact response is unique to each ECM, which is because of the inherent graft material, source, and processing techniques.61 Valentin et al.61 demonstrated differing remodeling patterns at nearly 4 months in a rat rotator cuff tear model. They found that controls showed typical scar formation, whereas the GraftJacket (allograft dermis) showed replacement with dense fibrous tissue, but a low-grade chronic inflammation (Fig. 1). The SIS (CuffPatch and Restore) was replaced with a mixture of cells including dense fibrous tissue, but a persistent foreign body re-

FIG. 1. ECM patch augmentation with allogeneic dermal tissue (GraftJacket) in an abdominal rat model demonstrates (A) at 7 days a dense mononuclear cell infiltrate limited to the edge of the device (arrows). (B) By 112 days, there was partial degradation of the GraftJacket device with replacement by moderately organized dense collagenous tissue (asterisk ⫽ original device; arrow ⫽ newly deposited collagen, Masson Trichrome). This compares to (C) a xenogeneic SIS (Restore) patch at 112 days after surgery which demonstrated that the device had been replaced by a vascularized connective tissue, with skeletal muscle randomly scattered within the tissue (arrows) and (D) a xenogeneic SIS (CuffPatch) at 112 days that showed moderate inflammatory response including a giant cell (arrow), with remnants of the implanted device (Asterisks) present. (Reproduced with permission from Valentin JE, et al. Extracellular matrix bioscaffolds for orthopaedic applications. J Bone Joint Surg 2006;88-A:2673–2686.) Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

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sponse in the CuffPatch device preferentially over the Restore implant. Xenogeneic dermis (TissueMend and Zimmer Collagen Repair Patch) demonstrated a lowgrade chronic inflammation, minimal scaffold degradation, and fibrous encapsulation, typical for a nonresorbable foreign material response.61 In addition, they demonstrated that the host vascular response was most notable in the SIS (Restore and CuffPatch) and allograft dermis (GraftJacket) implants. An in vitro study20 compared the effect of tenocytes on SIS and dermal grafts and demonstrated that the dermal graft (GraftJacket) was able to support ECM synthesis better by maintaining higher levels of growth factors (TGF-B1), matrix proliferation, and lower inflammatory cell counts compared with SIS, although both supported ECM integration. Nicholson and colleagues demonstrated in a comparison study of dermis to SIS, that by 9 weeks, macrophages were present on the dermal (Zimmer Collagen Repair Patch) grafts, which disappeared by 24 weeks. Vascular and fibroblastic integration was observed, without a foreign-body response. In the SIS group (Restore), most of the graft was resorbed by 9 weeks, and diverse tissue types were apparent. Others62 have shown that the SIS exhibited more prominent thinning of the graft material at 3 months versus the dermal allograft (GraftJacket) implant; the dermal allograft showed fibroblastic incorporation and better in-growth than the SIS. Although there remain significant differences in the cellular response of implanted grafts, it has not been clearly shown whether an early inflammatory response (as in the SIS patches) is more beneficial versus the generally more benign early responses of dermal grafts. Additional preclinical and human clinical work in this area is needed to determine which type of material is most amenable for rotator cuff augmentation. BIOMECHANICS OF BIOLOGIC ROTATOR CUFF PATCHES ECM Patch Augmentation Versus Intercalary Placement One of the critical concepts in the management of rotator cuff tears with ECM patches is the placement of the device. The ECM patch can be used in either an onlay augmentation (reinforcement) fashion— onlay of the device over a repaired tendon; versus ECM patch intercalary (interpositional) placement—the device between bone and retracted tendon). Although both techniques of ECM graft application have been described, the direct comparison and clinical application of each has yet to be fully elucidated. This is because of the complexity of the Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

characteristics of chronic, retracted rotator cuff tears, which demonstrate altered mechanics,26,27,52 muscle ultrastructure changes,27 and poorer tendon mechanics.17,26,27,52 In an intercalary biomechanical model2,19,44,66 the placement of an ECM graft has been shown to redirect force transmission and regenerate strength close to or surpassing that of native, intact cuff tendon. Augmentation (reinforcement) grafts have been shown to increase stiffness,53 with strength approaching that of native tendon (Table 2).39,45 When reading studies regarding the biomechanical and histologic evaluation of ECM patches, one should keep in mind the important distinction of graft application; augmentation versus intercalary, and interpret results accordingly. Biomechanical Testing of ECM Patches There is an extensive body of literature on the biomechanical testing of ECM patches for rotator cuff augmentation. One of the biomechanical principles of ECM implantation is that different collagen types present in SIS and dermis are different from that of the rotator cuff,57 preventing optimal biomechanical construct function. However, various techniques are currently available to engineer a graft with similar material properties of the native rotator cuff tendon.22,23,29,59,63 In an in vitro biomechanical testing model, Barber et 13 al. demonstrated that the GraftJacket (157 N-thin; 229 N-extreme) had a significantly higher load to failure than CuffPatch (32 N), Restore (38 N), Zimmer Collagen Repair Patch (128 N), and TissueMend (70 –76 N). The failure occurred by suture pullout. Overall, allograft human skin was the strongest (GraftJacket) followed by porcine (Zimmer), bovine skin (TissueMend), and SIS patches (Restore and CuffPatch). In animal models, augmentation of a rotator cuff tear with a 10 ⫻ 20 mm SIS patch demonstrated superior stiffness, but no increase in load-to-failure;53 however, the early healing characteristics of the construct were improved. Most SIS implants demonstrate the weakest strength from 1 to 2 weeks postimplantation in a preclinical model5,19,53,66 that rapidly increases over the next 3 to 12 months. By 3 months, most studies have demonstrated that the ultimate strength of the SIS implant is similar to a reimplanted tendon.19,66 In dermal interpositional grafts, the load to failure has been shown to be equivalent to control specimens by 12 weeks,2 and remained about the same from 3 months to 6 months (increased from 539 N at 3 months to 552 N at 6 months). Other mechanical properties such as ultimate stress, were equivalent to control groups at 6 months.

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TABLE 2. ECM Graft Application; Patch Onlay Augmentation (Reinforcement) Versus Intercalary (Interpositional) Reconstruction Model Augmentation (reinforcement) studies Iannotti et al.32 Human clinical Schlegel et al.53

Sheep

Intercalary (interpositional) studies Adams et al.2 Dog (adult mongrel)

Graft SIS

Histological Data Chronic inflammation 4 of 15 healed in augmentation group, 9 of 15 in controls No differences between SIS and untreated groups; both groups had gap formation, remnants of SIS patch were seen without evidence of foreign body reaction

N/A

Allogeneic dermal (GraftJacket)

6 w—inflammation consistent in both surgery and repair; 6 mo—control and experimental specimens mimicked normal tendons

Maximum force and ultimate stress not statistically different from control groups (except at 6 w, dermal patch statistically less) Less strength than that of native IS tendons, similar to reimplanted tendons at 3 and 6 mo Stiffness and yield strength 78% of normal at 16 w, but ultimate failure approached that of normal tendon

SIS

Dejardin et al.19

Dog (adult mongrel)

SIS

No foreign body or immune-mediated reactions

Zalavras et al.66

Rat

SIS

Fibroblastic in-growth, neovascularization, and collagenous ECM similar to native tendon

Xenogeneic dermis (Zimmer Collagen repair patch) vs. SIS (restore patch)

More inflammatory cells noted in SIS group; 9 w all SIS resorbed

SIS

10 of 11 failed by MRI with recurrence of large, retracted tears

Either augmentation or intercalary (in same study) Nicholson et al.45 Ewe

Sclamberg et al.55

Human

Biomechanical Data

No difference in SIS and control groups in load to failure; augmented SIS group had better stiffness

At 9 w: mean failure less in SIS repairs versus dermis; best in native tendons; at 24 w—failure loads identical N/A

Differences between augmentation (onlay) and intercalary (interpositional) ECM rotator cuff patch studies. SIS, small intestine submucosa; N/A, not applicable.

SURGICAL INDICATIONS AND TECHNIQUES Because of the relative avascular nature and low cell density of the rotator cuff tendons, healing of a rotator cuff tear is a slow process, and even in optimal conditions, the repair is comprised of a mechanically inferior tissue.15,27,54,60 Chronic, retracted tears of the rotator cuff present additional challenges in that the healing environment is not optimal, rotator cuff mechanics are altered, and tissue quality is further compromised.17,24,26,27,52 The treatment of patients with chronic, retracted tears of the rotator cuff, or those who present after a failed surgical repair remain a difficult subset of patients to achieve reliable postsurgical cuff healing.24 Surgical Indications The clinical indications for either ECM patch augmentation or interposition remain poorly defined. This is because of the relatively sparse clinical data as most of the literature is in the preclinical phase. However, several

studies have investigated the clinical application of ECM patches and defined their clinical indications for ECM use. Sclamberg et al.55 investigated 11 patients, all with atrophic, retracted 2-tendon rotator cuff tears of the supraspinatus and infraspinatus. They performed SIS grafting; 7 interpositional repairs (could not be repaired primarily) and 4 by reinforcement augmentation. Iannotti et al.32 randomized 32 patients with chronic (greater than 3 months) large or massive tears of the supraspinatus and infraspinatus, with a fully repairable tear without prior surgical intervention. They further classified large (4 –5 cm tears, retracted to the midpart of the humeral head) and massive (⬎5 cm, retraction medial to the midpart of the humeral head and moderate to severe muscle atrophy). All tendons were able to be repaired and were augmented with an SIS ECM onlay patch. Other studies with short follow up have used ECM patch augmentation43,48 in patients with cuff tears between 4 and 5 cm. Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

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Surgical Outcomes With only one randomized trial to date, the use of ECM patches has not been proven to be universally acceptable. Although most literature has described the use of ECM patches in chronic, large, and massive tear patterns, the clear indications remain poorly defined. Arguably, the most scientifically rigorous study to investigate the efficacy of an SIS ECM patch was performed by Iannotti32 and colleagues who randomized 30 shoulders to rotator cuff repair with and without SIS augmentation. Using postoperative magnetic resonance imaging (MRI) and intra-articular gadolinium, the rotator cuff healed in 4 of 15 shoulder augmented with SIS, versus 9 of 15 in the control group; outcomes scores were better in the control group. With adjustment for the effect of tear size, repairs without augmentation were 7% more likely to heal than those augmented with SIS. Three of the 15 shoulders treated with SIS developed a sterile inflammatory reaction, with a trend for the augmentation group to have a less favorable outcome. In conclusion, they did not recommend SIS augmentation for patients with the surgical indications and procedures they outlined. In addition, the study was stopped prematurely due to the inflammatory component in the SIS group as the authors felt that the augmentation was not improving the clinical result. Sclamberg et al.55 investigated 11 patients with 2-tendon tears; 7 patients had interpositional grafts and 4 were augmented. In short follow up, they found that the SIS scaffold did not allow for successful reconstruction of large to massive cuff tears, especially in the setting of muscle atrophy (10 of 11 failed by MRI). The authors felt that the SIS may not work for large and massive tears because 1) the ECM patch is only 1-mm thick (versus 5–10 mm normal cuff tendon); 2) the normal anatomy of the cuff is not recreated; 3) muscle pull may not be able to allow successful remodeling with fatty infiltration; and 4) inflammatory or immune rejection may play a small role. Malcarney et al.40 performed 25 SIS ECM patch procedures over a 6-month period and reported that 4 patients experienced an inflammatory reaction at a mean of 13 days postoperatively treated with open irrigation and debridement. The SIS patch was not present with risidual defects in the rotator cuff repair area. However, other reports41,43,48 have shown some degree of efficacy of dermal and SIS grafts in short-term follow up. Surgical Technique Both open and arthroscopic techniques have been described to perform ECM patch onlay augmentation or interposition. In the open technique, the rotator cuff tear is repaired with standard techniques using either bone tunnels, suture anchors, or a combination of both. If suture anchors Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

are used, the cuff can be secured to the bony anchor point; however, the ends of the sutures may be preserved to facilitate ECM augmentation repair. The retained suture limbs can be used to anchor the ECM patch in place. First, if applicable, the ECM patch needs to be fully hydrated. In the ECM augmentation technique, the ECM patch is trimmed to an appropriate size and placed in an onlay fashion onto the repaired rotator cuff tendons. Usually, the patch extends approximately 2 to 3 cm medial to the most lateral edge of the rotator cuff repair. If anchors are used for a medial row, the suture limbs after the cuff knots are tied may be used as initial anchor points. Once anchored medially, additional #2 braided polyester suture is placed approximately 5 mm apart to secure the medial attachment of the patch. At this point, the patch is gently stretched to take out any additional slack and potential sites of acromial impingement. The patch is then sewn with additional #2 braided polyester suture and sutured directly to the tendon. The most lateral aspect of the patch may be placed through bone tunnels, additional small anchors (3.5 mm), or sutured to intact rotator cuff tendon. The intercalary technique is similar, except the patch is sewn to the debrided edges of cuff tendon and anchored to the tuberosity in a tensionfree configuration. We have used a combination of arthroscopic and open techniques to accomplish ECM patch augmentation. A double-row transosseous equivalent technique, if performed, is followed by mini-open ECM patch augmentation. This provides medial row fixation, approximately 15 to 20 mm medial to the lateral edge of cuff attachment (Fig. 2). Utilizing 2 to 3 medial anchors, the rotator cuff medial row is tied and the sutures pulled out through the anterior portal (not cut). One limb from each of the anchor sites is used for a suture-bridge technique46 and secured with up to 3 PushLock (Arthrex, Naples, FL) devices in the lateral aspect of the tuberosity. Once tied, the suture limbs from the anchors and the PushLock’s can be used to achieve initial fixation of the ECM patch, with #2 braided polyester to fill the gaps at about 5 mm intervals. During transfer of the patch, the suture limbs from the anchors can be placed with the patch still outside the shoulder with a free needle and the patch shuttled down the anchor suture limbs. The patch is trimmed to obtain optimal coverage (2–3 cm medial to the lateral edge, and approximately 1 cm lateral to the lateral tendon edge, with anterior-posterior coverage over the tear). The final shape of the patch is generally ovoid. The ECM patch is palpated and the shoulder brought through a range of motion to ensure no prominences or acromial impingement areas. The mini open incision is closed with standard techniques. This procedure can be modified to perform an intercalary (inter-

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FIG. 2. A 47-year-old male with failed chronic, massive rotator cuff tear 8 months after initial repair attempt (A, B) demonstrates intact anchors and suture knots from initial surgery (suggesting biologic failure) but a large amount of cuff retraction in a massive tear configuration. The humeral head is prepared (C) for a double-row transosseous equivalent repair with a SutureBridge technique (D). The cuff repair is augmented with an allogeneic dermal ECM patch (GraftJacket) with a mini-open technique (E) and sutured into place using remaining suture limbs from 2 medial anchors and 3 lateral PushLocks (Arthrex, Naples, FL). Additional #2 polyester braided suture is placed in simple vertical fashion to ensure no prominences and smooth tracking under the acromion.

positional) repair; however, we recommend that the majority of the interpositional repair be performed via open techniques. All-arthroscopic augmentation techniques have been described36,56 and are similar to the above technique, except that the ECM patch is brought through a cannula. Suture management is critical to the success of arthroscopic procedures, and accessory portals are used when necessary (anterolateral, posteromedial) to

“park” sutures and avoid tangling and twists. Mulberry knots have been advocated56 placed in the 4 corners of the repair to facilitate graft passage down the lateral cannula with a trocar. Additional suture may be placed to completely secure the graft in place with a variety of available suture passers. Alternatively, anchors may be used to accomplish a 4-quadrant repair. Each limb is retrieved through the central-lateral cannula to appropriately tension and secure the graft. Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

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The majority of ECM patch complications in the clinical setting have centered around the relatively low healing rate of cuff repairs augmented with ECM patches. The overall rate of preserved cuff integrity after repair and augmentation with SIS patch is between 5% to 30%.32,55 Only 1 of 11 large and massive rotator cuff repairs augmented with SIS patch evaluated with an MRI at 6 months demonstrated continuity of repair.55 In another study, Iannotti32 demonstrated that only 4 of 15 had an intact cuff tendon. An acute inflammatory response has been described with the clinical use of SIS patches,32,40,55 although dermal allograft and xenograft inflammatory reactions are also present in an animal model.2 The inflammatory response in 2 reports32,40 was severe enough to warrant additional surgical intervention for irrigation and debridement in the acute healing period (mean 2 weeks). Range of motion did not appreciably increase,55 and there is some evidence of early stiffness associated with the procedure; however, this may be because of a more protective postoperative range of motion protocol in the setting of a massive rotator cuff tear repair.24,26

CONCLUSIONS The use of ECM biologic patches for the treatment of chronic, large, and massive rotator cuff tears is an emerging field. An extensive amount of basic science and preclinical models have demonstrated that an ECM patch may offer improved healing rates with a biomechanical profile that nearly reproduces the characteristics of the native rotator cuff tendon. Unfortunately, the small amount of available clinical evidence has not been as encouraging, which underscores the difficulties in extrapolating animal rotator cuff studies to human application. In addition, one should keep in mind the exact use of the ECM patch when interpreting studies— either as an augmentation (onlay) versus interpositional (intercalary) technique, which may significantly alter the overall efficacy of the ECM patch. In regards to specific patches, the SIS (porcine derived) has shown a higher inflammatory response in the early stages, with resorption of the graft material; however, dermal grafts (both allogeneic and xenogeneic sources) also demonstrate some degree of inflammatory response, but less resorption of the graft. It remains difficult to say whether the degree of early inflammatory response is beneficial to the overall healing process. The use of ECM patches for either Techniques in Orthopaedics®, Vol. 22, No. 1, 2007

augmentation or intercalary repair of chronic large and massive rotator cuff tears continues to evolve; however, predictable clinical results have yet to be demonstrated.

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