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P-15 is a 15-amino-acid-long biomimetic peptide widely demonstrated to enhance osteogenesis in vivo. Despite the prevalence of polyether-ether-ketone (PEEK) in interbody device manufacturing, a growing body of evidence suggests it may produce an unfavorable immune response. The purpose of this preliminary study was to characterize the immune response and new bone growth surrounding PEEK implants with and without a P-15 peptide-based osteobiologic. A bilateral femoral defect model was conducted using New Zealand white rabbits. A total of 17 test subjects received one implant in each distal femur, either with or without bone graft material. Animals were allowed to survive to 4 or 8 weeks, at which time the femurs were collected and subjected to micro-computer tomography (microCT) or cytokine analysis. MicroCT analysis included the quantification of bone growth and density surrounding each implant. The cytokine analysis of periprosthetic tissue homogenates included the quantification of interleukins (ILs) and TNF-α expression via ELISA kits. Improvements in bone volume were observed in the P-15 cohort for the regions of interest, 500–136 and 136–0 µm from the implant surface, at 8 weeks post-op. Concentrations of IL-1β, IL-4, and IL-6 cytokines were significantly higher in the P-15 cohort compared to the PEEK cohort at the 4-week timepoint. Significant reductions in the concentrations of IL-4 and IL-6 cytokines from the 4- to 8-week cohort were observed in the P-15 cohort only. The P-15 peptide has the potential to modulate the immune response to implanted materials. We observed improvements in bone growth and a more active micro-environment in the P-15 cohort relative to the PEEK control. This may indicate an earlier transition from the inflammatory to remodeling phase of healing.

Musculoskeletal (MSK) pathology encompasses an array of conditions that can cause anything from mild discomfort to permanent injury. Their prevalence and impact on disability have sparked interest in more effective treatments, particularly within orthopedics. As a result, the human placenta has come into focus within regenerative medicine as a perinatal derivative (PnD). These biologics are sourced from components of the placenta, each possessing a unique composition of collagens, proteins, and factors believed to aid in healing and regeneration. This review aims to explore the current literature on PnD biologics and their potential benefits for treating various MSK pathologies. We delve into different types of PnDs and their healing effects on muscles, tendons, bones, cartilage, ligaments, and nerves. Our discussions highlight the crucial role of immune modulation in the healing process for each condition. PnDs have been observed to influence the balance between anti- and pro-inflammatory factors and, in some cases, act as biologic scaffolds for tissue growth. Additionally, we assess the range of PnDs available, while also addressing gaps in our understanding, particularly regarding biologic processing methods. Although certain PnD biologics have varying levels of support in orthopedic literature, further clinical investigations are necessary to fully evaluate their impact on human patients.

Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes.

The rapid rise in deaths since 2012 due to opioid poisoning is correlated with the proliferation of potent synthetic opioid agonists such as fentanyl, acrylfentanyl, and carfentanil. The efficacy of frontline antidotes such as naloxone in reversing such poisoning events has been questioned, and the possibility of naloxone-resistant synthetic opioids has been raised. In this manuscript, we applied in vitro techniques to establish the median effective inhibitory concentrations for fentanyl, acrylfentanyl, and carfentanil and subsequently evaluate naloxone’s ability to reverse agonist–receptor interactions.

Background: Effective triage - directing patients with low back pain to appropriate treatment or correct referral - is fundamental to quality care. Without guidelines, a physician's initial decision may lead to unnecessary investigation, unneeded intervention or unwarranted consultation.Methods: To compare the functional outcomes of patients triaged by a classification based on clinical presentation with those of patients selected at the clinicians’ discretion, an insurance-owned hospital network employed forty-seven specially-trained physical therapists, working within participating primary care practices, to classify low back pain patients into specific Patterns of Pain. Between October 2017 and April 2019, the primary care physicians used this classification, derived entirely from the patient's history and physical examination, to direct subsequent treatment for 260 consecutive low back pain patients. Patients with systemic symptoms, recent substantial trauma or non-mechanical diagnoses indicative of spinal infections or possible malignancy were excluded. Functional outcome measures were spinal imaging, opioid use, length of treatment and number of visits, back-related unplanned care, frequency of spinal surgery and back-related episode cost. These were compared with a control group of 256 propensity-matched patients and, for assessing the financial impact, with a historic cohort of 111 previously treated, non-classified patients.Results: Spinal imaging: study group 24.5%; controls 42.2% (P< .001). Narcotic use: study group 4.6%; controls 13.3% (P< .001). Treatment length: study group 62.2 days; controls 74.5 days (P=.10). Treatment visits: study group 1528 visits; controls 2,046 visits (P=.003). Unplanned care: study group 1.9%; controls 12.8% (P< .001). Spine surgery: study group 15.4%; controls 26.2% (P=.005). Episode cost: study group $1453; controls $2334 (P=.005).Conclusions: A well-defined clinically-based triage system produced meaningful reductions in imaging, opioid use, treatment duration, unplanned interventions, surgery and cost of care.

Introduction. Pedicle based posterior dynamic stabilization systems aim to stabilize the pathologic spine while also allowing sufficient motion to mitigate adjacent level effects. Two flexible constructs that have been proposed to act in such a manner, the Dynesys Dynamic Stabilization System and PEEK rod, have yet to be directly compared in vitro to a rigid Titanium rod. Methods. Human lumbar specimens were tested in flexion extension, lateral bending, and axial torsion to evaluate the following conditions at L4-L5: Intact, Dynesys, PEEK rod, Titanium rod, and Destabilized. Intervertebral range of motion, interpedicular travel, and interpedicular displacement metrics were evaluated from 3rd-cycle data using an optoelectric tracking system. Results. Statistically significant decreases in ROM compared to Intact and Destabilized conditions were detected for the instrumented conditions during flexion extension and lateral bending. AT ROM was significantly less than Destabilized but not the Intact condition. Similar trends were found for interpedicular displacement in all modes of loading; however, interpedicular travel trends were less consistent. More importantly, no metrics under any mode of loading revealed significant differences between Dynesys, PEEK, and Titanium. Conclusion. The results of this study support previous findings that Dynesys and PEEK constructs behave similarly to a Titanium rod in vitro.