A supramolecular polymer-collagen microparticle slurry for bone regeneration with minimal growth factor.

Recombinant bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive growth factor that can promote bone regeneration for challenging skeletal repair and even for ectopic bone formation in spinal fusion procedures. However, serious clinical side effects related to supraphysiological dosing highlight the need for advances in novel biomaterials that can significantly reduce the amount of this biologic. Novel biomaterials could not only reduce clinical side effects but also expand the indications for use of BMP-2, while at the same time lowering the cost of such procedures. To achieve this objective, we have developed a slurry containing a known supramolecular polymer that potentiates BMP-2 signaling and porous collagen microparticles. This slurry exhibits a paste-like consistency that stiffens into an elastic gel upon implantation making it ideal for minimally invasive procedures. We carried out in vivo evaluation of the novel biomaterial in the rabbit posterolateral spine fusion model, and discovered efficacy at unprecedented ultra-low BMP-2 doses (5 µg/implant). This dose reduces the growth factor requirement by more than 100-fold relative to current clinical products. This observation is significant given that spinal fusion involves ectopic bone formation and the rabbit model is known to be predictive of human efficacy. We expect the novel biomaterial can expand BMP-2 indications for difficult cases requiring large volumes of bone formation or involving patients with underlying conditions that compromise bone regeneration.

Distal Radius Fractures: Recognizing and Treating Complex Fracture Patterns.

SUMMARY: Volar fixed-angle plate fixation is a commonly used treatment modality for distal radius fractures. However, not all fracture patterns are amenable to this type of fixation strategy. In this article, we review pertinent anatomy and radiographic landmarks that together highlight key differences when considering treatment strategies for complex distal radius fractures.

Effect of Postoperative Analgesic Exposure to the Cannabinoid Receptor Agonist WIN55 on Osteogenic Differentiation and Spinal Fusion in Rats.

BACKGROUND: After spinal surgery and other orthopaedic procedures, most patients receive opioids for pain, leading to potential complications such as pseudarthrosis and opioid abuse associated with long-term use. As an alternative, the endocannabinoid system has been shown to have antinociceptive activity, while contributing to bone homeostasis via the CB1 and CB2 cannabinoid receptors. This study evaluates the impact of the cannabinoid receptor agonist WIN55,212-2 (WIN55) on osteogenic differentiation in vitro as well as bone regeneration and spinal fusion in a preclinical rat model. METHODS: Primary rat bone marrow stromal cells were cultured in standard or osteogenic media and exposed to vehicle alone or WIN55. Runx2 and Alkaline phosphatase (Alpl) were quantified via qPCR (quantitative real-time polymerase chain reaction), followed by assessment of ALP activity and matrix mineralization. For in vivo evaluation, 45 female Sprague Dawley rats (n = 15 per group) underwent L4-L5 posterolateral spinal fusion with bilateral placement of collagen scaffolds preloaded with low-dose rhBMP-2 (recombinant human bone morphogenetic protein-2; 0.5 µg/implant). Postoperatively, rats received the vehicle alone or 0.5 or 2.5 mg/kg WIN55 via daily intraperitoneal injections for 5 days. Bone regeneration and spinal fusion were assessed using radiography, manual palpation-based fusion scoring, microcomputed tomography imaging, and histology. RESULTS: mRNA expression levels of Runx2 and Alp were similar among cells treated with vehicle alone and WIN55. Likewise, exposure to WIN55 did not inhibit ALP activity or bone matrix mineralization. In this animal model, no significant differences were found among groups with regard to mean fusion score, fusion rate, or new bone volume. CONCLUSIONS: WIN55 showed no adverse impact on osteogenic differentiation, bone regeneration, and spinal fusion. This supports that cannabinoid receptor agonists should be further investigated as a potential alternative approach for postoperative analgesia following spinal fusion and other orthopaedic procedures requiring bone-healing. CLINICAL RELEVANCE: The identification of alternative treatments for postoperative pain following orthopaedic surgical procedures is crucial in combating the ongoing opioid abuse crisis. The endocannabinoid system may represent a viable alternative target for addressing orthopaedic postoperative pain.

Performance Outcomes and Return-to-Sport Rate of National Hockey League Athletes Vary After Common Orthopedic Surgical Procedures.

OBJECTIVE: Evaluate performance-based outcomes and return-to-sport rate in National Hockey League (NHL) athletes. DESIGN: Retrospective cohort study. SETTING: Public records. No direct patient care was provided. PARTICIPANTS: National Hockey League athletes who underwent different orthopedic procedures were identified using public records. Three hundred thirty-seven athletes met inclusion criteria. INDEPENDENT VARIABLES: Common orthopedic surgical procedures in NHL athletes. MAIN OUTCOME MEASURES: Return-to-play and preoperative and postoperative performance measures were collected to calculate a position-specific performance score. Short-term and medium-term outcomes were defined as 1 and 2 to 3 seasons after surgery, respectively. RESULTS: Three hundred seven athletes (92.6%) successfully returned to play. The number of games played during the first season after surgery compared with baseline was significantly decreased for hip arthroscopy (HA), noninstability shoulder arthroscopy (ie, shoulder arthroscopy procedure to address pathology other than shoulder instability), knee arthroscopy, and sports hernia repair (P = 0.002, 0.009, 0.03, and 0.01, respectively). The number of games played for seasons 2 and 3 after surgery was significantly decreased for both HA and noninstability shoulder arthroscopy (P = 0.01 and 0.001, respectively). Short-term postoperative performance scores were significantly decreased for HA, noninstability shoulder arthroscopy, and anterior cruciate ligament reconstruction (P = 0.00004, 0.02, and 0.02, respectively) while medium-term scores were significantly decreased for HA only (P = 0.009). CONCLUSIONS: National Hockey League athletes return to play at a high rate after common orthopedic surgeries. However, certain procedures portend poorer performance scores and game participation than others. In particular, HA and noninstability shoulder arthroscopy have the greatest negative effect on NHL careers after surgery.

Influence of Geometry and Architecture on the In Vivo Success of 3D-Printed Scaffolds for Spinal Fusion.

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model. Inks containing HA and DBM particles in a poly(lactide-co-glycolide) elastomer were 3D-printed into scaffolds with varying relative strut angles (90° vs. 45° advancing angle), macropore size (0 µm vs. 500 µm vs. 1000 µm), and strut alignment (aligned vs. offset). The following configurations were compared with scaffolds containing no macropores: 90°/500 µm/aligned, 45°/500 µm/aligned, 90°/1000 µm/aligned, 45°/1000 µm/aligned, 90°/1000 µm/offset, and 45°/1000 µm/offset. Eighty-four female Sprague-Dawley rats underwent spine fusion with bilateral placement of the various scaffold configurations (n = 12/configuration). Osteointegration and vascularization were assessed by using microComputed Tomography and histology, and spine fusion was assessed via blinded manual palpation. The 45°/1000 µm scaffolds with aligned struts achieved the highest average fusion score (1.61/2) as well as the highest osteointegration score. Both the 45°/1000 µm/aligned and 90°/1000 µm/aligned scaffolds elicited fusion rates of 100%, which was significantly greater than the 45°/500 µm/aligned iteration (p < 0.05). All porous scaffolds were fully vascularized, with blood vessels present in every macropore. Vessels were also observed extending from the native transverse process bone, through the protrusions of new bone, and into the macropores of the scaffolds. When viewed independently, scaffolds printed with relative strut angles of 45° and 90° each allowed for osteointegration sufficient to stabilize the spine at L4-L5. Within those parameters, a pore size of 500 µm or greater was generally sufficient to achieve unilateral fusion. However, our results suggest that scaffolds printed with the larger pore size and with aligned struts at an advancing angle of 45° may represent the optimal configuration to maximize osteointegration and fusion capacity. Overall, this work suggests that the HA/DBM composite scaffolds provide a conducive environment for bone regeneration as well as vascular infiltration. This technology, therefore, represents a novel, growth-factor-free biomaterial with significant potential as a bone graft substitute for use in spinal surgery. Impact statement We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed composite material comprising hydroxyapatite and demineralized bone matrix for bone regeneration. Here, we identify a range of 3D geometric and architectural parameters that support the preclinical success of the scaffold, including efficient vascularization, osteointegration, and, ultimately, spinal fusion. Our results suggest that this material holds great promise as a clinically translatable biomaterial for use as a bone graft substitute in orthopedic procedures requiring bone regeneration.

Effect of Statewide Social Distancing and Stay-At-Home Directives on Orthopaedic Trauma at a Southwestern Level 1 Trauma Center During the COVID-19 Pandemic.

OBJECTIVES: To compare orthopaedic trauma volume and mechanism of injury before and during statewide social distancing and stay-at-home directives. DESIGN: Retrospective. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: One thousand one hundred thirteen patients sustaining orthopaedic trauma injuries between March 17 and April 30 of years 2018, 2019, and 2020. INTERVENTION: Statewide social distancing and stay-at-home directives. MAIN OUTCOME MEASUREMENTS: Number of consults, mechanism of injury frequency, and type of injury frequency. RESULTS: During the COVID-19 pandemic, orthopaedic trauma consult number decreased. Injuries due to gunshot wounds increased and those due to automobile versus pedestrian accidents decreased. Time-to-presentation increased and length of stay decreased. Operative consults remained unchanged. CONCLUSIONS: Orthopaedic trauma injuries continued to occur during the COVID-19 pandemic at an overall decreased rate, however, with a different distribution in mechanism and type of injury. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

3D-Printed Ceramic-Demineralized Bone Matrix Hyperelastic Bone Composite Scaffolds for Spinal Fusion.

Although numerous spinal biologics are commercially available, a cost-effective and safe bone graft substitute material for spine fusion has yet to be proven. In this study, "3D-Paints" containing varying volumetric ratios of hydroxyapatite (HA) and human demineralized bone matrix (DBM) in a poly(lactide-co-glycolide) elastomer were three-dimensional (3D) printed into scaffolds to promote osteointegration in rats, with an end goal of spine fusion without the need for recombinant growth factor. Spine fusion was evaluated by manual palpation, and osteointegration and de novo bone formation within scaffold struts were evaluated by laboratory and synchrotron microcomputed tomography and histology. The 3:1 HA:DBM composite achieved the highest mean fusion score and fusion rate (92%), which was significantly greater than the 3D printed DBM-only scaffold (42%). New bone was identified extending from the host transverse processes into the scaffold macropores, and osteointegration scores correlated with successful fusion. Strikingly, the combination of HA and DBM resulted in the growth of bone-like spicules within the DBM particles inside scaffold struts. These spicules were not observed in DBM-only scaffolds, suggesting that de novo spicule formation requires both HA and DBM. Collectively, our work suggests that this recombinant growth factor-free composite shows promise to overcome the limitations of currently used bone graft substitutes for spine fusion. Impact Statement Currently, there exists a no safe, yet highly effective, bone graft substitute that is well accepted for use in spine fusion procedures. With this work, we show that a three-dimensional printed scaffold containing osteoconductive hydroxyapatite and osteoinductive demineralized bone matrix that promotes new bone spicule formation, osteointegration, and successful fusion (stabilization) when implemented in a preclinical model of spine fusion. Our study suggests that this material shows promise as a recombinant growth factor-free bone graft substitute that could safely promote high rates of successful fusion and improve patient care.

Prognosis Following Hip Arthroscopy Varies in Professional Athletes Based on Sport.

PURPOSE: To evaluate return to play (RTP) and performance-based outcomes in professional athletes across 4 major North American team sports following hip arthroscopy. METHODS: Professional athletes of the National Football League, Major League Baseball (MLB), National Basketball Association, and National Hockey League (NHL) who underwent hip arthroscopy were identified using an established protocol of public reports. Sport-specific statistics were collected before and after hip arthroscopy for each athlete, leading to a performance score. RTP was defined as the first regular or postseason game played following surgery. RESULTS: A total of 151 arthroscopic hip procedures were performed on 131 professional athletes. The overall RTP rate after arthroscopic hip surgery was found to be 88.7% (134 of 151 arthroscopic hip surgeries), with no significant difference between sports. The median number of seasons played after hip arthroscopy were 2.7, 2.3, 1.1, and 0.9 for the National Football League, National Basketball Association, MLB, and NHL cohorts, respectively, with no significant difference between sports. MLB and NHL cohorts experienced a decrease in games played in the first season following hip arthroscopy (P = .04, P = .01), whereas NHL players also experienced a decrease in games played in seasons 2 and 3 postoperatively (P = .001). Performance scores decreased in the NHL cohort for all seasons postoperatively (P < .001, P = .003). No other statistically significant differences were found when comparing players of different sports. CONCLUSIONS: Although professional athletes demonstrate a high rate of RTP following hip arthroscopy across the 4 major North American team sports, hockey players demonstrate the worst prognosis following hip arthroscopy, with sustained decreases in games played and performance in the first 3 seasons postoperatively. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Differential effects of buffer pH on Ca(2+)-induced ROS emission with inhibited mitochondrial complexes I and III.

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca(2+), a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca(2+) loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca(2+) and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III.