Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc.

An model that appropriately recapitulates the degenerative disc disease (DDD) microenvironment is needed to explore clinically relevant cell-based therapeutic strategies for early-stage degenerative disc disease. We developed an advanced 3D nucleus pulposus (NP) microtissues (µT) model generated with cells isolated from human degenerating NP tissue (Pfirrmann grade: 2-3), which were exposed to hypoxia, low glucose, acidity and low-grade inflammation. This model was then used to test the performance of nasal chondrocytes (NC) suspension or spheroids (NCS) after pre-conditioning with drugs known to exert anti-inflammatory or anabolic activities.

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease.

Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform.

Posterior stabilization with polyetheretherketone (PEEK) rods and transforaminal lumbar interbody fusion (TLIF) with titanium rods for single-level lumbar spine degenerative disease in patients above 70 years of age.

Background: Given the lack of guidelines regarding the operative management of elderly patients needing lumbar spine fusion for degenerative disease, it is often difficult to balance between invasiveness respecting the fragile spine and geriatric comorbidities.

Aim: To compare reoperation rates and clinical outcome in patients above 70 years of age undergoing Transforaminal Lumbar Interbody Fusion (TLIF) with titanium rods or posterior stabilization with Polyetheretherketone (PEEK) rods for the treatment of one-level lumbar spine degenerative disease.

Methods: Retrospective review of baseline characteristics, reoperation rates as well as the clinical and radiological outcomes of patients, older than 70 years, undergoing posterolateral fusion with PEEK rods (n = 76, PEEK group) or TLIF with titanium rods (n = 67, TLIF group) for a single-level lumbar degenerative disease from 2014 to 2020.

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc.

Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. Although regenerative cell-based strategies have shown promise in clinical trials, none have been widely adopted clinically. Recent developments demonstrated that spheroid-based approaches might help overcome challenges associated with cell-based IVD therapies.

Computed tomography osteoabsorptiometry for imaging of degenerative disc disease.

Background: Lower back pain is a common condition with significant morbidity and economic impact. The pathophysiology is poorly understood but is in part attributable to degenerative disc disease (DDD). The healthy intervertebral disc ensures spine functionality by transferring the perceived load to the caudally adjacent vertebrae.

Intervertebral Disc-on-a-Chip as Advanced Model for Mechanobiology Research and Drug Testing: A Review and Perspective.

Discogenic back pain is one of the most diffused musculoskeletal pathologies and a hurdle to a good quality of life for millions of people. Existing therapeutic options are exclusively directed at reducing symptoms, not at targeting the underlying, still poorly understood, degenerative processes. Common intervertebral disc (IVD) disease models still do not fully replicate the course of degenerative IVD disease.

Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation.

Cell-based strategies for nucleus pulposus (NP) regeneration that adequately support the engraftment and functionality of therapeutic cells are still lacking. This study explores a scaffold-free approach for NP repair, which is based on spheroids derived from human nasal chondrocytes (NC), a resilient cell type with robust cartilage-regenerative capacity. We generated NC spheroids (NCS) in two types of medium (growth or chondrogenic) and analyzed their applicability for NP repair with regard to injectability, biomechanical and biochemical attributes, and integration potential in conditions simulating degenerative disc disease (DDD).

Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc.

Nasal chondrocytes (NCs) have gained increased recognition for cartilage tissue regeneration. To assess NCs as a source for cell therapy treatment of intervertebral disc (IVD) degeneration, tissue-forming properties of NCs under physiological conditions mimicking the degenerated IVD were compared to those of mesenchymal stromal cells (MSCs) and articular chondrocytes (ACs), two cell sources presently used in clinical trials. Cells were cultured in a combination of low glucose, hypoxia, acidity and inflammation for 28 d.

Challenges Toward the Identification of Predictive Markers for Human Mesenchymal Stromal Cells Chondrogenic Potential.

Human bone marrow derived mesenchymal stromal cells (BMSCs) represent a putative cell source candidate for tissue engineering-based strategies to repair cartilage and bone. However, traditional isolation of BMSCs by adhesion to plastic leads to very heterogeneous cell populations, accounting for high variability of chondrogenic differentiation outcome, both across donors and across clonally derived strains. Identification of putative surface markers able to select BMSC subpopulations with higher chondrogenic capacity (CC) and reduced variance in chondrogenic differentiation could aid the development of BMSC-based cartilage and bone regeneration approaches.

An In Vitro Bone Model to Investigate the Role of Triggering Receptor Expressed on Myeloid Cells-2 in Bone Homeostasis.

Triggering receptor expressed on myeloid cells-2 (TREM-2), a transmembrane receptor expressed by macrophages, microglia, and osteoclasts (OCs), plays a protective role in late-onset Alzheimer Disease (AD). To validate TREM-2 as a therapeutic target in AD, its potential secondary parallel effect on bone homeostasis should be clarified. However, animal models and monolayer cultures of human cells were shown poorly predictive of TREM-2 function in human.

Minimum ten-year follow-up of spinal stenosis with degenerative spondylolisthesis treated with decompression and dynamic stabilization.

Background: The Dynesys system remains the most widely implanted posterior non-fusion pedicle screw system. Various study designs used in investigations with good to excellent short- and mid-term results have been reported in the current literature. However, there is a lack of information concerning long-term outcomes following treatment for spinal stenosis with degenerative spondylolisthesis.

Spatially confined induction of endochondral ossification by functionalized hydrogels for ectopic engineering of osteochondral tissues.

Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized that the embedding of cells inducible to endochondral ossification (i.e.

Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood.

Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs.

Notochordal cell-derived conditioned medium protects human nucleus pulposus cells from stress-induced apoptosis.

Background Context: Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society.

Purpose: Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells.

Study Design/setting: This is an "in vitro" fundamental or basic science study.

Notochordal cell conditioned medium (NCCM) regenerates end-stage human osteoarthritic articular chondrocytes and promotes a healthy phenotype.

Background: Notochordal cell conditioned medium (NCCM) derived from non-chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators.

Preoperative and Postoperative Factors and Laboratory Values Predicting Outcome in Patients Undergoing Lumbar Fusion Surgery.

Objective: To determine whether complications in lumbar fusion surgery could be estimated from patient factors and perioperative laboratory values. In addition, risk scores for detection of patients prone to complications were defined.

Methods: We retrospectively collected data of patients undergoing lumbar fusion surgery between 2013 and 2015.

Effectiveness of the addition of Lidocaine to a hemostatic, bioresorbable putty in the treatment of iliac crest donor site pain.

Background: The harvest of iliac crest bone grafts (ICBG) is associated with relevant donor site pain, but may be lowered by the application of lidocaine loaded on biodegradable, hemostatic putty for sustained local analgesic release. The goal of this double-blind controlled trial was to assess the efficacy of adding lidocaine to a hemostatic putty (Orthostat ™) to treat donor site pain following harvest of ICBG in foot and ankle procedures.

Methods: After ICBG harvest during a foot and ankle procedure, the resulting bone defect was either filled with Orthostat™ (n = 7) or with the same hemostatic putty loaded with lidocaine (Orthostat-L™, n = 7).

Tension Pneumothorax as a Complication of Inadvertent Pleural Tears During Posterior Spinal Surgery.

Objective: To review and expose the occurrences of tension pneumothorax as a result of pleural tear during posterior spinal surgery.

Methods: Intraoperative reports were retrospectively reviewed for 2 patients who underwent posterior spinal fusion and experienced pleural tear and subsequent tension pneumothorax. Surgical decisions for recognition and treatment were also reviewed.

Non-adherent mesenchymal progenitors from adipose tissue stromal vascular fraction.

In primary human bone marrow cultures, the initial adherent cell fraction has been shown to provide a microenvironment for self-renewal of primitive non-adherent mesenchymal progenitors (non-adherent progenitors of bone marrow stroma [BM-NAMP]), with increased differentiation potential compared to adherent colony-forming units-fibroblast (CFU-f). The present study investigates whether NAMP exist also in cultures of stromal vascular fraction (SVF) cells derived from human adipose tissue. Adipose-tissue NAMP (AT-NAMP) were shown to be stably non-adherent and their number correlated with the number of the initial adhering CFU-f.

Substitutes of structural and non-structural autologous bone grafts in hindfoot arthrodeses and osteotomies: a systematic review.

Background: Structural and non-structural substitutes of autologous bone grafts are frequently used in hindfoot arthrodeses and osteotomies. However, their efficacy is unclear.The primary goal of this systematic review was to compare autologous bone grafts with structural and non-structural substitutes regarding the odds of union in hindfoot arthrodeses and osteotomies.

Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2.

Engineered osteogenic constructs for bone repair typically involve complex and costly processes for cell expansion. Adipose tissue includes mesenchymal precursors in large amounts, in principle allowing for an intraoperative production of osteogenic grafts and their immediate implantation. However, stromal vascular fraction (SVF) cells from adipose tissue were reported to require a molecular trigger to differentiate into functional osteoblasts.

Tissue engineering approaches to degenerative disc disease--a meta-analysis of controlled animal trials.

Objective: The objective of this systematic review was to assess cell/biomaterial treatments of degenerative disc disease in controlled animal trails. The primary endpoints were restoration of disc height and T2 signal intensity.

Method: PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) were searched for studies reporting on the use of tissue engineering treatments (cells/biomaterials/cells and biomaterials) for degenerative disc disease treatments in a controlled trial.

Fibroblast growth factor-2 maintains a niche-dependent population of self-renewing highly potent non-adherent mesenchymal progenitors through FGFR2c.

Bone marrow (BM) mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here, we show that primary human BM cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering colony-forming units-fibroblast (CFU-f).