Intervertebral disc (IVD) degeneration occurs with aging, leading to low back pain (LBP), which is one of the leading conditions of disability worldwide. With the lack of effective treatment, decellularized extracellular matrix (dECM) – based biomaterials have been proposed for IVD regeneration. However, the impact of donor ages on tissue repair had never been explored before in the disc field. Therefore, we aimed to address this question.

For that, a decellularization protocol for bovine nucleus pulposus (NP) of different aged donors (fetus, young and old) was optimized by testing several detergents (SDS and Triton). The process efficiency was evaluated in terms of DNA and cell removal, as well as ECM preservation. Afterwards, dECMs were repopulated with bovine NP cells and cultured ex vivo. At day 7, cell behavior, ECM de novo synthesis and remodeling were evaluated [1]. Moreover, dECMs’ inflammatory response was assessed after in vivo CAM assay. Finally, inflammatory and angiogenic cytokines were analyzed in the conditioned media-derived from dECMs by using a cytokine array.

As results, an optimal decellularization protocol (SDS 0.1%, 1h), efficient at removing cells and DNA from bovine NPs, while preserving ECM cues of native tissues, was developed. After repopulation, aggrecan increased in younger NPs, while collagen 2 decreased which may be indicative of matrix remodeling [1]. After in vivo CAM assay, fetal dECMs showed the highest inflammatory response. Finally, no statistically significant changes of cytokines were detected in the matrices, despite for a trend of higher IFN-α, IFN-γ and LIF in fetal dECMs, IL-1β in young dECMs and Decorin in old dECMs.

Overall, this work uncovered the importance of tissue donor ages for tissue regenerative purpose, opening new avenues for the development of appropriate therapeutic strategies for IVD degeneration.

Acknowledgments: FCT, EUROSPINE, ON Foundation.

Introduction The frequency of spine surgery in the elderly continues to increase in parallel with the overall aging of the population. The main goal of this study was to determine if age is a risk factor for major complications in spine surgery. In addition, other co-morbidities and the relationship with age and potential for major complications were explored.

Methods All adult patients undergoing spine surgery at our center over a four-year period were included in this study, for a total of 1937 patients (605 age 18 – 39; 1001 age 40–64, 331 age 65 and over). One independent observer abstracted baseline medical histories and co-morbidities as well as post-operative complications. Major risk factors explored included history of cardiac, cancer, smoking, diabetes, substance abuse, obesity, respiratory problems, previous infections and hypercholesterolemia. Details of surgical procedure, including type of surgery, duration of surgery and blood loss were also captured. Major complications were defined as death, CVA, embolism, pneumonia and deep wound infections.

Patients ranged in age from 18 years to 91 (average age 48 years) and 41% were males. Thirty percent of the population was deformity patients, 49% degenerative patients and the remaining 21% had various other spine problems. Thirty-five percent of the patients underwent a combined anterior posterior procedure, 13% anterior alone and 34% posterior alone.

Statistical analysis included descriptive summary, vicariate correlation to assess individual risk factors (university analysis) and multivariate regression.

Results The overall major complication rate was 2.1% (40 patients). There were no intra- or post-operative deaths. Major complications included 7 CVA (0.4%), 2 embolisms (0.1%), 3 deep wound infections (0.2%) and 28 pneumonia (1.4). For patients age 65 or older,

Overall, 61% of the patients had at least one of the major risk factors. The number of major risk factors increased with increased age. The percent of patients with any given risk factor also increased with age.

When no other factors were taken into account (such as co-morbidities), there was an increased occurrence of a major complication (any one), pneumonia and infection with increased age at time of surgery. In order to differentiate the effect due to age and due to co-morbidities (which increased with age), multivariate regression was utilized. For the occurrence of any major complication, the presence of respiratory problems and previous infection were both more influential than age. Furthermore, when the effects of these two risk factors were controlled for, there no longer was an effect due to age.

Discussion Older patients did not have an increased rate of major complications when compared to younger patients with similar respirator and infection history profiles.