Bioresorbable technology has been in clinical use by surgeons for over 35 years.1 Physicians in several different specialties, including craniomaxillofacial surgery, neurosurgery, orthopedic surgery, and general surgery, have successfully used implants and products that eventually degrade in the body2 for a wide variety of reconstructive procedures. In orthopedic surgery, bioresorbable implants are today most frequently used in sports medicine, foot and ankle, shoulder, and spine surgery. Because of the many advantages of bioresorbable products compared with their traditional metallic counterparts, their use in spine surgery has expanded over the last several years (Figure 1).
Resorbable polymer implants, similar to nonresorbable polymer implants, have the advantage of being radiolucent, thus facilitating radiographic and imaging analysis of the status of the interbody fusion. Uniquely and perhaps more importantly, resorbable implants manufactured from polylactic acid slowly degrade into carbon dioxide and water over a 12- to 18-month period, allowing anterior column structural support to gradually shift from the implant to the maturing interbody fusion mass.3–6 While there have been published series that have demonstrated encouraging preliminary results of bioresorbable polymers in interbody fusion, to date there have been no clinical series to be published with a minimum follow-up of 2 or more years.7,8
This report documents clinical results of the use of a hollow cylindrical bioresorbable interbody spacer, (Hydrosorb Mesh, Medtronic Sofamor Danek, Inc.; Memphis, TN) and outlines the basic research, animal studies, and preliminary clinical trials using bioresorbable materials in spine surgery. The Hydrosorb material used in this series is a copolymer consisting of a 70:30 ratio of poly-L-lactide and D,L-lactide (PLDLA) and can be manufactured into a variety of shapes and sizes. This material as used in the unilateral transforaminal lumbar interbody arthrodesis procedure (TLIF) in this series is formed into hollow cylinders, comparable in geometry to the titanium mesh cages available by the same manufacturer (Figure 2).
The TLIF procedure is an interbody arthrodesis combined with a unilateral posterior (facet and/or interlaminar) arthrodesis with or without a bilateral posterolateral arthrodesis that is stabilized with pedicle screw instrumentation. This is a variation of the posterior lumbar interbody fusion (PLIF) technique first described by Cloward and popularized and modified by others as a surgical treatment option for lumbar disc disease.9–15 The details of this procedure as performed in this series have been described in detail elsewhere.7,8
From December 2001 until September 2002, 31 patients (22 males and 9 females) with a mean age of 45.5 years (range, 30–64 years) underwent the TLIF procedure at a total of 58 levels (mean, 1.9 levels per patient; range, 1–3 levels) for a variety of lumbar conditions using two 13-mm × 8- to 12-mm PLDLA bioresorbable spacers per interbody fusion level for anterior column support (116 total spacers implanted). Two additional patients underwent posterior fusion at one additional (transitional L5–S1) level without supplemental anterior column support. One patient with a Grade 1 isthmic spondylolisthesis at L5–S1 below previous anterior fusion from L2–L4 for an L3 burst fracture underwent the TLIF procedure at L4–L5 and L5–S1 with instrumentation and posterior fusion from L2 to S1. Nine patients in this series had previous decompressive lumbar surgery at one or more of the operated levels. One patient had a previous TLIF procedure with metallic cages at L3–L4 and L4–L5 3 years before her TLIF procedure at L5–S1 with Hydrosorb spacers. All of the patients in this series had low back pain as their predominant complaint, with varying degrees of radicular pain and neurologic complaints. All patients were operated by one of the authors (J.D.C.) at a single institution. All patients underwent at least 12 months of nonoperative care before coming to surgery. Twenty-one patients (67%) underwent treatment for work-related disorders of their lumbar spine. All patients in this series (100.0%) had some component of degenerative disc disease. A complete listing of the other diagnoses is shown in Table 1. The most cephalad operated level in this series was L2–L3. The distribution of levels fused is shown in Table 2. The mean estimated blood loss was 1,070 mL (range, 350–3,500 mL), and the mean postoperative length of stay was 5.1 day (range, 2–11 days).
Assessment of Results.
Anteroposterior, lateral, and Ferguson view lumbar radiographs were obtained at 2 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. Standing flexion-extension lateral films were obtained as well, beginning with the 6-month set. Fusion status was judged on the 12-month and the 24-month films using the criteria listed in Table 3. The clinical results of this study were analyzed using the method of Prolo et al.12 Twenty-seven of the 31 operated patients were available for 24 month follow-up. Additionally, in a subset of 16 patients, the SF-36 outcomes instrument was administered before surgery, 12 months after surgery in 19 patients and 24 months after surgery. The preoperative, 12-month and 24-month postoperative scores were compared and analyzed for the purposes of this study.
Mean follow-up for the 27 patients in this series with minimum follow-up of 24 months was 31.9 months (range, 28–37 months). Four postoperative complications were noted in 3 of 27 patients (11.1%) and are listed in Table 4. None of these complications was attributable to the use of the bioresorbable polymer. One patient (3.7%) was noted to have one cracked implant immediately after insertion. No subsidence or other evidence of further structural failure has been subsequently observed in this patient, and he was judged to be solidly fused at his most recent follow-up. No patient has experienced any evidence of allergic or inflammatory reactions to the polymer. Specifically, there have been no adverse events either directly or indirectly related to the use of the bioresorbable implants.
One patient (3.7%) developed a nonunion as determined by obvious motion on flexion-extension lateral radiographs obtained after increasing complaints of low back pain at 9 months postoperative and has undergone subsequent revision surgery. Another patient who was initially thought to be solidly fused became increasingly symptomatic over 2 years after surgery. He was noted to have a solid posterolateral fusion radiographically and on CT; his interbody fusion, however, had not united as noted on coronal and sagittal CT reconstructions (Figure 3). This patient is pending anterior revision. The remaining 25 patients (92.6%), however, have progressed to a solid fusion as illustrated in Figure 4.
Using the method of Prolo et al,12 22 of the 27 patients (81.5%) had good to excellent results, 5 patients (14.8%) had a fair result, and 1 patient (3.7%). One of the patients with nonunion had a poor result (as assessed before his revision surgery), and the other patient with interbody nonunion and solid posterolateral fusion had a fair result. SF-36 outcomes analysis in 16 demonstrated a statistically significant improvement in the 12- and 24-month mean pain scores and 24-month mean role physical scores compared with the preoperative scores on the same scales (Figure 5). Other SF-36 scores showed improvement, but only some reached statistical significance.
A variety of resorbable polymers has been used in clinical medicine, mostly (PLA) and polyglycolic acid (PGA) and derivatives, from the family of α-polyesters. These substances degrade in the body into glycolic acid and lactic acid, substances normally found in the body. In studies of these α-polyesters, PGA has been shown to degrade faster than PLA.3–6 As a result of its faster degradation time, PGA, when used alone, has demonstrated a greater incidence of sterile inflammatory reactions. Different combinations and variations in processing of bioresorbable substances can be used to alter their degradation time and physical properties. Isomeric forms (levo and dextro) of a polymer, i.e., PLA, when combined, can minimize the incidence of soft tissue reactions and inflammation in both animals and humans.
At the present time, there are two FDA cleared resorbable materials that are most commonly used in orthopedic and/or neurosurgical applications. The first is a copolymer of poly-L-lactic acid/poly-glycolic acid (PLA/PGA) that retains 70% of its strength for 6 to 9 weeks, with nearly complete strength loss at 12 weeks, and essentially complete resorption (mass loss) within 12 months. The other is a copolymer PLDLA, which retains approximately 100% strength at 3 months, 70% strength for 6 to 9 months, and 50% at 12 months and resorbs between 18 and 36 months.6 The PLDLA implant used in the series described in this report is made of the latter copolymer, which has what is thought to be the ideal spinal implant characteristics, including a slow degradation with retention of strength over a sufficiently long period to provide stability, while the interbody fusion mass matures, and progressively assumes anterior column loading over time (load sharing). Resorption of the PLDLA implants occurs by bulk hydrolysis into carbon dioxide and water; thus, there are no detrimental degradation products.5 The use of other bioresorbable polymers in clinical applications, including craniomaxillofacial surgery, hand surgery, infertility surgery and nerve regeneration surgery, has also been reported.16–21
A theoretical advantage of a bioresorbable implant is that it initially provides the biomechanical stability of a traditional metallic implant but with a modulus of elasticity much more similar to bone compared with its metallic counterpart. van Dijk et al22 compared the biomechanical properties of poly-L-lactide (PLLA) lumbar interbody cages with traditional metallic cages (titanium) in explanted lumbar spines from 21 Dutch goats. The compressive properties of the native spine segments were determined and used to design flexible or stiff bioresorbable PLLA cages by varying the cage wall thickness. In comparison with titanium cages, the bioresorbable cages were found to provide sufficient initial mechanical stability as an interbody fusion device. Overall, this study demonstrated the potential of using an appropriately designed resorbable cage as a lumbar interbody fusion and stabilization device.
The majority of animal studies to date have used sheep and goat models for test subjects. Several biomechanical features, in particular the response to axial loading, were found to be similar between the sheep and goat and the human spine in several trials.22–36 Toth et al33 investigated the use of stand-alone resorbable threaded interbody spine implants manufactured from PLDLA (the same 70:30 polymer used in this series) in a goat model, comparing autograft versus rhBMP-2. Their study demonstrated no significant inflammatory response related to the polymer and gradual replacement of the polymer spacer by precursors of osseous tissue and ultimately bone, indicating good biocompatibility in the 12-, 18-, and 24-month groups of sheep. In the 12-month group, two of four sheep (one autograft, one rhBMP-2) achieved fusion and two (one autograft and one rhBMP-2) did not achieve fusion ostensibly because of increased segmental mobility related to mechanical degradation of the resorbable polymer spacers. In the 18- and 24-month groups, however, all five sheep (three autograft and two rhBMP-2) went on to solid fusion determined both radiographically and histologically. Based on the findings of the study, the authors concluded that a PLDLA cage is a possible alternative to the use of a traditional metallic cage in interbody fusions.
Wuisman et al34 compared the efficacy of pure PLLA resorbable cages (flexible and stiff designs) to a metallic interbody spacer for single-level fusion in a goat model. Follow-up ranged from 3 to 30 months. Fusion success, which was assessed radiographically at 6 months, was noted in 80% of all the specimens. A decreased rate of bone formation was found with the metallic cages, a consequence of stress shielding according to the investigators. In this study, bone remodeling was complete at the 2-year assessment in the bioresorbable cage group. At the 3-year follow-up, almost all the PLLA cages were completely degraded. A mild inflammatory reaction was noted during the absorption process with the resorbable cages.
Concerns about the safety of bioresorbables have been addressed in several studies.6,33,37–40 Poly-lactic acid (PLA) biocompatibility has been demonstrated with both dural and neural tissues within the spinal cord by Lundgren et al.40 Gautier et al37 have shown the presence of PLA to have no effect on neuronal cells, non-neuronal cells, or axon growth in rat spinal cords. Similarly, de Medinaceli et al38 have demonstrated biocompatibility with peripheral nerves on both gross and histologic examination. Van der Elst et al39 have also demonstrated an absence of local tissue pH changes associated with the degradation of PLA implants placed in the femoral shafts of sheep.
Only preliminary and intermediate clinical results of the use of PLDLA spacers in the lumbar spine have been reported to date.7,15 Lowe and Coe7 reported the preliminary results in a combined (two-center) series of 60 patients who underwent the TLIF procedure with PLLA hollow cylindrical cages. Early clinical results were found to be encouraging in that study, but follow-up was short (mean, 4.7 months; longest follow-up, only 9 months). However, no complications attributable to the use of the resorbable implants were noted. Coe reported an 18- to 24-month follow-up in a subset of the above series (and a superset of the current series) with similar encouraging results.11 This latter report was the first published series in which the mean follow-up time (18.4 months) equaled or exceeded the life expectancy of the implant.11
Austin et al41 evaluated the use of a bioresorbable interbody spacer inserted posteriorly with adjunctive pedicular fixation in the treatment of symptomatic lumbar degenerative disc disease. At 1-year follow-up, all patients were noted to have a successful clinical outcome and radiographic evidence of fusion. The only complication noted was delayed wound healing in 1 patient.
Recently, Herceg et al42 reported the results of large diameter thin-walled (2 mm) PLDLA spacers with rhBMP-2 in a series of 22 patients treated anterior interbody fusion and posterior pedicle screw fixation at one or two levels (total of 40 levels fused). Although a high percentage of the levels fused (88%) went on to solid fusion, 60% of levels fused experienced significant subsidence (>7 mm). Two patients in this series underwent revision posterolateral fusion. The authors speculated that the small “footprint” of PLDLA spacer (in contrast to the FRA), without the additional interbody structural support of additional graft material (i.e., morsalized autograft or allograft) resulted in a “telescoping” effect of the implant subsiding into the vertebral bodies through the endplate. Furthermore, structural endplate integrity in this series was compromised by the use of a jig-guided cylindrical drill for endplate preparation in all of the patients in this series. The authors’ hypothesis is consistent with biomechanical data from Closkey et al43 that recommends a minimum 25% to 30% threshold for endplate coverage by interbody spacers.
In general, surgical techniques that include both posterolateral and interbody fusion have demonstrated high fusion rates and good clinical results.10,12,14,44,45 These procedures have distinct advantages including anterior column load sharing, large surface areas for fusions, restoration of a normal sagittal profile, and the achievement passive foraminal decompression.10,12,14,44,45 The posterior unilateral transforaminal approach allows the surgeon to concurrently address all of these issues through one approach without the need for a second anterior incision and its associated morbidity and complications (particularly vascular complications in all patients and retrograde ejaculation in male patients). As compared with the PLIF, the TLIF has the advantage of requiring exposure and manipulation of the neural elements (for the purposes of achieving interbody fusion) on only one side per level, and even that only minimally.
This is the first series to report the clinical results of interbody fusion using spacers manufactured with the poly-L-lactide-co-D,L-lactide copolymer, with follow-up period that significantly exceeds the biologic “life expectancy” of the material (12–18 months). All of the procedures were performed by a single surgeon at a single institution with 87.1% follow-up. Clinical results are equivalent to those published in comparable series that use nonresorbable spacers for interbody structural support, particularly noteworthy given the fact that over two thirds of the patients in this series were from a traditionally difficult patient population (workers’ compensation).10,12,14,44,45
Limitations of this study include a relatively small series size (27 patients), lack of a control group in which nonresorbable implants were used, and incomplete SF-36 data on all patients. Nevertheless, this series represents the largest series of the clinical use of bioresorbable polymer interbody implants yet published, with a mean follow-up exceeding 31 months.
Bone morphogenetic protein (rhBMP-2) appears to be well suited for use in combination with resorbable polymer interbody implants.36 One of the authors began to use rhBMP-2 in conjunction with morselized allograft with PLDLA spacers in the TLIF procedure since the fall of 2002. The preliminary results have been encouraging in the 46 cases performed to date with less blood loss, shorter length of stay, and, most significantly, earlier than achievement of fusion compared with the cases reported in this series.46 These patients will be formally reported when 2-year follow-up has been achieved in most of these patients.
At this time, favorable clinical results have been demonstrated in interbody fusion, anterior spinal plate applications, and as protective barriers. The lack of imaging artifact and gradual transfer of local stresses to the surrounding spinal units makes resorbable technology extremely attractive in spinal reconstructive procedures. The future of bioresorbable technology in spinal surgery appears to be quite exciting and will see the use of these polymers not only for structural support and graft containment but also for pharmacologic and growth factor administration.
This study evaluated the clinical and radiographic results in 27 patients from one center who underwent instrumented transforaminal lumbar interbody fusion using cylindrical bioresorbable polymer spacers manufactured with a 70:30 copolymer of poly-L-lactide and D,L-lactide (PLDLA) and iliac crest autograft bone for primarily degenerative indications. At a mean of 31.9 months follow-up, 25 patients (92.6%) were judged to have solid fusions, and 22 patients (81.5%) had good to excellent results. Three patients (11.1%) experienced complications, none of which were directly or indirectly attributable to the use of the bioresorbable polymer implant. Only one implant in 1 patient (3.7%) demonstrated mechanical failure on insertion without clinical sequelae. This is the first clinical series to be published with a minimum follow-up of 2 years, significantly exceeding the biologic “life expectancy” of this material (12–18 months). Both the clinical and radiographic results of this study support the use of interbody devices manufactured from biodegradable polymers for structural interbody support in the transforaminal lumbar interbody fusion procedure.
- Bioresorbable implants possess advantages in both imaging (less artifact) and biomechanics (less stress shielding over time) compared with comparable metallic implants.
- Two-year follow-up in a series of 27 patients undergoing the TLIF procedure using resorbable PLDLA cages for interbody support demonstrate a satisfactory fusion and clinical success rate without evidence of significant complications directly attributable to the use of the resorbable material.
- Follow-up in this series (mean, 31.9 months) exceeds the biologic “life expectancy” of the bioresorbable material (12–18 months).
- Bioresorbable as interbody spacers are suitable for use in lumbar spine fusion with the TLFI technique.
The authors thank the Sarmad Pirzada, MD, MPH, for his assistance in the preparation of the SF-36 data reported in this paper.
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