RESUMO
BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-ß (TGFß) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFß signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined. METHODS: Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFß-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing. RESULTS: Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery. CONCLUSION: We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue. LEVEL OF EVIDENCE: Level V.
Assuntos
Síndrome de Loeys-Dietz , Ligamento Patelar , Fator de Crescimento Transformador beta2 , Animais , Modelos Animais de Doenças , Síndrome de Loeys-Dietz/genética , Metaloproteinase 2 da Matriz , Camundongos , Ligamento Patelar/fisiopatologia , Ligamento Patelar/cirurgia , Tendões/fisiopatologia , Tendões/cirurgia , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta2/fisiologia , CicatrizaçãoRESUMO
Interbody fusion is a workhorse technique in lumbar spine surgery that facilities indirect decompression, sagittal plane realignment, and successful bony fusion. The 2 most commonly employed cage materials are titanium (Ti) alloy and polyetheretherketone (PEEK). While Ti alloy implants have superior osteoinductive properties they more poorly match the biomechanical properties of cancellous bones. Newly developed 3-dimensional (3D)-printed porous titanium (3D-pTi) address this disadvantage and are proposed as a new standard for lumbar interbody fusion (LIF) devices. In the present study, the literature directly comparing 3D-pTi and PEEK interbody devices is systematically reviewed with a focus on fusion outcomes and subsidence rates reported in the in vitro, animal, and human literature. A systematic review directly comparing outcomes of PEEK and 3D-pTi interbody spinal cages was performed. PubMed, Embase, and Cochrane Library databases were searched according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Mean Newcastle-Ottawa Scale score for cohort studies was 6.4. A total of 7 eligible studies were included, comprising a combination of clinical series, ovine animal data, and in vitro biomechanical studies. There was a total population of 299 human and 59 ovine subjects, with 134 human (44.8%) and 38 (64.4%) ovine models implanted with 3D-pTi cages. Of the 7 studies, 6 reported overall outcomes in favor of 3D-pTi compared to PEEK, including subsidence and osseointegration, while 1 study reported neutral outcomes for device related revision and reoperation rate. Though limited data are available, the current literature supports 3D-pTi interbodies as offering superior fusion outcomes relative to PEEK interbodies for LIF without increasing subsidence or reoperation risk. Histologic evidence suggests 3D-Ti to have superior osteoinductive properties that may underlie these superior outcomes, but additional clinical investigation is merited.