Fibrous tissue ingrowth and attachment to porous tantalum

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1 Fibrous tissue ingrowth and attachment to porous tantalum S.A. Hacking, 1,2,4 J.D. Bobyn, 1-4 K.-K. Toh, 1 M. Tanzer, 1-3 J.J. Krygier 1 1 Jo Miller Orthopaedic Research Laboratory, LS1-409, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4 2 Division of Orthopaedics, McGill University, S 9.30, 687 Pine Avenue W, Montreal, Quebec, Canada H3A 1A1 3 Department of Surgery, McGill University, Montreal General Hospital, D6-136, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4 4 Department of Biomedical Engineering, McGill University, Lyman Duff Medical Sciences Building, 3775 University Street, Montreal, Quebec, Canada H3A 2B4 Received 26 August 1999; accepted accepted 25 February 2000 Abstract: This study determined the soft tissue attachment strength and extent of ingrowth to a porous tantalum biomaterial. Eight dorsal subcutaneous implants (in two dogs) were evaluated at 4, 8, and 16 weeks. Upon retrieval, all implants were surrounded completely by adherent soft tissue. Implants were harvested with a tissue flap on the cutaneous aspect and peel tested in a servo-hydraulic tensile test machine at a rate of 5 mm/min. Following testing, implants were dehydrated in a solution of basic fuschin, defatted, embedded in methylmethacrylate, and processed for thin-section histology. At 4, 8, and 16 weeks, the attachment strength to porous tantalum was 61, 71, and 89 g/mm respectively. Histologic analysis showed complete tissue ingrowth throughout the porous tantalum implant. Blood vessels were visible at the interface of and within the porous tantalum material. Tissue maturity and vascularity increased with time. The tissue attachment strength to porous tantalum was three- to six-fold greater than was reported in a similar study with porous beads. This study demonstrated that porous tantalum permits rapid ingrowth of vascularized soft tissue, and attains soft tissue attachment strengths greater than with porous beads John Wiley & Sons, Inc. J Biomed Mater Res, 52, , Key words: tantalum; porous; soft tissue; attachment; implant INTRODUCTION For over two decades a wide variety of porous polymeric and metallic implants have been used in reconstructive procedures as scaffolds for mechanical attachment by tissue ingrowth. 1 9 The most notable and common example is the use of porous biomaterials for the biologic fixation of prostheses in joint replacement surgery. 1,4,10-14 In these applications, the porous materials are designed for bone ingrowth to enhance implant fixation in order to withstand the mechanical demands of load bearing joints. Extensive information has been published on the effects of using parameters such as pore size, pore volume, pore depth on bone ingrowth, and the extent and rate of attachment strength in both experimental and clinical contexts. 15 Also studied, although to a lesser extent, is the use of porous biomaterials in procedures involving soft tissue ingrowth. Much of this research has involved Correspondence to: S.A. Hacking; ahacking@ yahoo.com Contract grant sponsor: The Medical Research Council of Canada 2000 John Wiley & Sons, Inc. studies of the anchorage of percutaneous devices made from materials such as Dacron velour, 8,9,16 titanium and stainless steel fiber mesh, and hydroxyapatite ceramics Other studies have focused on the use of polytetrafluorethylene-based porous implants for abdominal defect repairs or maxillofacial reconstruction. 6,25 27 Porous coated cobalt-chromium alloy implants have also been evaluated for soft tissue ingrowth and attachment strength in orthopedic applications, with the aim of ligament or tendon attachment or tumor replacement implants in which vascularized soft tissue ingrowth could provide both biomechanical and biological benefits These studies have generally shown that fibrous tissue readily heals within porous structures, less so if pores are smaller than about 50 m, and more so with greater vascularity and attachment strength as pore size, porosity, and implantation time increase. Recently, a porous tantalum biomaterial has been developed that possesses a high volumetric porosity dodecahedron and a highly interconnected network of consistent, shaped pores. Previous studies have indicated the suitability of this porous tantalum biomaterial for biologic fixation by bone ingrowth in both functional and nonfunctional animal implant mod-

2 632 HACKING ET AL. els The material is characterized by quicker bone ingrowth rates and better interface strength development, as compared to conventional porous metals such as sintered beads and fiber metal. The geometry of the material, combined with its mechanical properties and ease with which it can be manufactured into complex shapes, are factors conducive to applications involving soft tissue as well as bone ingrowth. The purpose of this study was to characterize the fibrous tissue ingrowth and strength of attachment to porous tantalum in a canine implant model. MATERIALS AND METHODS Material fabrication and characterization Figure 2. Microtexture of porous tantalum struts. The fabrication process of the porous tantalum begins with the pyrolysis of a thermosetting polymer foam precursor in order to obtain a low-density carbonaceous foam skeleton possessing a repeating dodecahedron array of pores (cells) interconnected by smaller openings (portals). Using chemical vapour deposition/infiltration (CVD/CVI) techniques, commercially pure tantalum is deposited into and about the carbon skeleton to create a porous metal construct (Fig. 1). As the tantalum is progressively deposited onto the carbon struts, the structural integrity of the construct increases. Because of crystallographic growth and orientation of the tantalum during deposition, the process results in a surface with a distinct microtexture (Fig. 2). A typical tantalum coating thickness is approximately 40 to 60 m. By varying the characteristics of the polymer precursor and the thickness of the tantalum coating, the pore size of the material can be varied. For orthopaedic applications, the average pore size is typically in the range of 400 to 600 m. The volume porosity of the material ranges from 75 to 80%, depending on the tantalum coating thickness. The mechanical Figure 1. SEM of porous tantalum structure showing interconnected porosity. properties of the material also vary with tantalum coating thickness. The bulk porous structure possesses a compressive elastic modulus of 2.5 to 3.9 GPa, an ultimate compressive strength of 50 to 70 MPa, a static torsional strength of 40 to 60 MPa, and a 10 million cycle endurance limit in fourpoint bending of MPa. 32 Implants Rectangular implants 30 mm long, 20 mm wide, and 6 mm thick were fabricated from bulk porous tantalum (Fig. 3). All edges were slightly beveled to reduce stress concentration by tissue at the implant site. There was a 2 mm diameter hole at each corner of the implant to allow the passage of a suture for securing the implant at the time of surgery. Study protocol Following the protocol of a prior study on soft tissue attachment to sintered beaded porous surfaces, 24 implants were placed in the dorsal subcutaneous tissue of six mongrel dogs using standard aseptic surgical techniques. Approval for animal research was granted by the McGill institutional review board and performed in strict accordance to the guidelines of the Canadian Council on Animal Care. Along the same side of the spine, two 4 cm skin incisions, perpendicular to and 8 cm lateral of the spine were made in each dog. The first incision was made 4 cm caudal to the scapula, the second 15 cm posterior. On either side of each incision, a soft tissue pocket between the subcutaneous fat and the underlying fascia was created using sharp dissection. One implant was placed into each pocket and secured into position with two # 1 Vicryl (Ethicon, Sommerville, New Jersey) sutures at opposite corners. Prior to incision closure the implant sites were gently irrigated with saline. Following surgery the animals were administered analgesics for a period of 24 hours and allowed to recover without limitations to diet or activity. Two animals (eight implants) were studied

3 FIBROUS TISSUE INGROWTH AND TANTALUM 633 Figure 3. Porous tantalum implant. at each time period of 4, 8, and 16 weeks. Animals were sacrificed by barbiturate overdose. Mechanical testing The implants were dissected from the surrounding tissues with a 4 cm flap of overlying subcutaneous tissue attached to it. The specimens were kept moist in isotonic saline solution and prepared for immediate testing. Careful removal of all tissue along the sides of the implant subjected only tissue on the cutaneous aspect of the implant to the peel test. The implant was clamped along its sides in a horizontal position in the lower jaw of a servo-hydraulic Instron (Canton, Massachusetts) tensile test machine. The attached flap of tissue was clamped in the upper jaw and adjustments were made to start each mechanical test with the tissue flap perpendicu- Figure 4. Soft tissue peel test. Tissue flap attached to jaws of servo-hydraulic tensile test machine. Vascularity of tissue is evident.

4 634 HACKING ET AL. Following mechanical testing, the soft tissues around and within each implant were stained for collagen by immersion in a 0.4% solution of basic fuschin in ethanol for 6 days. 34 In preparation for thin section histology the specimens were fixed in formalin, dried in ascending solutions of alcohol, and defatted in ether/acetone prior to embedding in polymethylmethacrylate. Sections 1 mm thick were cut transversely through the center of each implant with a low-speed diamond saw, mounted to Plexiglass slides with cyanoacrylate glue, and progressively thinned to a thickness between 50 and 100 m using petrographic grinding techniques. The thinned sections were protected with a coverslip and viewed with transmitted light microscopy. The stained sections were primarily used to confirm the presence and extent of soft tissue ingrowth within the implant and the presence of vascularity within the newly formed tissue. The density of the fibrous tissue was qualitatively assessed as a function of implantation time to provide an impression of collagen content and maturity. RESULTS Intraoperative and postoperative observations Figure 5. Schematic representation of typical loaddisplacement curve recorded during a mechanical test. Calculation of average maximal peel force (g/mm) from line of best fit. lar to the implant surface (Fig. 4). A distraction force was applied to the tissue flap at a rate of 5 mm/minute; this resulted in progressive peeling of the tissue off the implant surface. The attachment force was measured by a 25 N load cell. Testing was periodically interrupted to reposition the implant in the lower jaw so as to maintain the tissue flap within 10 of perpendicularity of the implant surface. During testing, care was taken to ensure adequate tissue hydration with isotonic saline. Testing progressed until the tissue flap had been peeled from about half of the implant length. The maximum attachment force was obtained by calculating the average of the maximal readings of the load cell over the length of the test (Fig. 5), divided by the width of the implant (20 mm) in order to obtain the peel attachment strength in g/mm. Histologic analysis In all cases, manipulation of the implants into the soft tissue pockets required extreme care because of the strong tendency for soft tissue adherence to the rough texture of the tantalum porous network. In one case, swelling and fluid developed around the implant within the first week of surgery; it resolved without intervention or complications. There were no postoperative infections. At the time of harvest all implants were surrounded with soft fibrous tissue that was firmly attached to the implant surface. No bursa formed around any of the implants. Mechanical testing During mechanical testing, small blood vessels were clearly visible at the implant surface as tissue was peeled away, suggestive of neovascularization within the porous tantalum (Fig. 4). The tissue adherence to the porous tantalum appeared uniform across the implant width at all time periods. It appeared that failure of the tissue/implant interface resulted from soft tissue rupture outside the implant, as opposed to mechanical pullout from within the implant pores. It was often observed that tissue would tear within the attached flap instead of at the implant surface, indicating that the tissue-implant interface was at least as strong as the surrounding tissue itself. In order to ensure continuous peeling away of tissue at or near the implant surface, it was often necessary to use a scalpel TABLE I Results of Mechanical Peel Tests (g/mm) for Each Implant at 4, 8, and 16 Weeks Test # Mean ± SD 4 weeks ± weeks ± weeks ± 43.1

5 FIBROUS TISSUE INGROWTH AND TANTALUM 635 Figure 6. Histologic section at 4 weeks showing complete ingrowth of fibrous tissue through the implant (basic fuschin). to re-establish the preferred failure plane. The mean tissue attachment strength was 60.7 ± 37.4 g/mm at 4 weeks, 70.9 ± 37.5 g/mm at 8 weeks, and 89.4 ± 43.1 g/mm at 16 weeks (Table 1). Data were normally distributed. The differences in attachment strength between time periods were not statistically significant (t test, ANOVA). Histologic analysis At the time of explantation all implants were enveloped by soft tissue that was firmly attached to the implant surface. Gross histologic analysis showed that the adherent soft tissue was present throughout the entirety of all implants for all three study periods (Fig. 6). The ingrown tissue appeared as densely ordered bundles, high in collagen content and vascularity (Fig. 7). At all study periods the ingrown tissue formed intimate contact with the porous tantalum struts with few intervening spaces. The organization and density of the ingrown tissue was greatest within a 2 mm region at the implant periphery. As implantation time progressed, from 4 to 16 weeks, the density, organization, and vascularity of ingrown tissue increased. The histologic findings supported observations made during mechanical testing. Examination of the location and amount of tissue at the edges of the implant crosssections confirmed that tissue failure occurred at or beyond the implant surface, with no noticeable pulling out of tissue from within the implant pores. The thickness of the sections precluded a quantified histomorphometric analysis of cell types within the fibrous tissue, although erythrocytes within nutrient vessels were clearly identifiable (Fig. 7). DISCUSSION This study demonstrated the potential of the porous tantalum material to allow rapid ingrowth of vascu- Figure 7. Vascularized fibrous tissue ingrowth at 16 weeks. Erythrocytes are present in nutrient vessel (basic fuschin).

6 636 HACKING ET AL. larized soft tissue with attachment strength that is essentially equivalent to that of surrounding tissue. Within 4 weeks of surgery, the histologic sections showed ingrowth across the full-implant depth (6 mm). Mechanical testing at 4 weeks indicated that substantial attachment strength had been attained. At the 8- and 16-week time periods, the ingrown tissue appeared denser and more vascular, as would be expected in the case of normal tissue healing. Although statistical differences in attachment strength were not detected beyond 4 weeks, there was a trend toward stronger attachment with increasing tissue maturity. A larger sample size might well have indicated statistical increases in attachment strength with time. The measured attachment strengths were in the range of the inherent tensile breaking load per unit width of various animal soft tissues, corroborating the visual and histologic observations of tissue failure within the adjacent tissue flap during mechanical testing. 16,35 37 The implant model used in this study has previously been reported upon for the initial evaluation of biomaterials for soft tissue ingrowth. 28 The peel test was originally adapted from standard methods for assessing the attachment strength of adhesive tapes, and was described in previous studies that measured the peel strength of soft tissue growth into porous coatings made of sintered cobalt-chrome beads. 28,30 Compared with the study of Bobyn et al. in which the peel strength was measured as a function of three different pore sizes, the strengths of attachment measured in the present study were several fold greater. With sintered beaded porous coatings possessing an average pore size of about 90 m, Bobyn et al. measured maximum strengths of 12 g/mm, 18 g/mm, and 28 g/mm at 4, 8, and 16 weeks, respectively. In the present study with the porous tantalum material, the average tissue attachment strength was sixfold, fivefold, and threefold greater at 4, 8, and 16 weeks, respectively. Furthermore, in the present study there were no samples in any test period where the attachment strength did not exceed the average attachment strength for the porous samples of Bobyn et al. 28 Factors that would contribute to additional strength of the porous tantalum implants relate to the geometry and high frictional coefficient of porous tantalum which were observed at surgery to be very effective for immediate soft tissue adhesion. 38 The larger pore size of the tantalum material may also contribute to increased attachment strength; other studies have shown larger pores to be conducive to well-vascularized and well-organized tissue ingrowth. 17,18,28 30,39 41 The increased strength might be most strongly related to the higher inherent porosity of porous tantalum, which is at least twofold higher than sintered porous coatings, and thus allows more tissue to develop at the interface and contribute to strength development. It has also been suggested that a high porosity is a requisite for the sustenance and development of fibrous tissue with a porous material. Compared to osseous tissue, fibrous tissue is more cellular and would be expected to possess greater metabolic demands. As a result, the large porosity of the tantalum material would present a greater volume for both new tissue and new vascular formation. Although the histologic method precluded identification and quantification of inflammatory cells around the porous tantalum material, there is a long history of use of commercially pure tantalum in surgical implant applications and it has been shown to possess excellent biocompatibility Tantalum is a strong, ductile metal with very high oxidation and corrosion resistance. 9,33 Beginning about five decades ago it has been used for pacemaker electrodes, 46 cranioplasty plates, 47 ligation clips, 48 femoral endoprostheses, wire, foil, and mesh for nerve repair, 49 and radiopaque markers for following bone growth and implant migration. 44,50 Osseointegration has previously been demonstrated with nonporous tantalum implants in dental and orthopaedic applications for periods as long as 8 to 12 years. 51,52 Recent animal studies have documented the suitability for bone ingrowth of the porous tantalum structure used in the present soft tissue study. 31 Overall, the properties of tantalum have led to its standardization as a surgical implant material. 35,43,50 In certain orthopaedic reconstructive procedures, it would be beneficial to have a porous biomaterial that enables attachment to both bone and soft tissue structures. This includes tendon and ligament reattachment in both upper and lower extremities. It could also include tissue attachment for custom devices used for salvaging joint reconstructions or tumor replacement prostheses. The mechanical and physical properties of porous tantalum, together with its tissue ingrowth characteristics, represent a useful combination for such applications. The results of this study support further development of the porous tantalum biomaterial for clinical use. The authors are grateful to the Implex Corporation for providing the implants. References 1. Cameron HU, Macnab I, Pilliar RM. A porous metal system for joint replacement surgery. Int J Artif Organs 1978;1: MacGregor DC, Wilson GJ, Lixfeld W, Pilliar RM, Bobyn JD, Silver MD, Smardon, S, Miller SL. The porous-surfaced electrode: a new concept in pacemaker lead design. J Thorac Cardiovasc Surg 1979;78: Picha GJ, Drake RF. 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