A rhPDGF-BB/bovine type I collagen/ß-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

Finding the Goldilocks Zone of Mechanical Loading: A Comprehensive Review of Mechanical Loading in the Prevention and Treatment of Knee Osteoarthritis.

In this review, we discuss the interaction of mechanical factors influencing knee osteoarthritis (KOA) and post-traumatic osteoarthritis (PTOA) pathogenesis. Emphasizing the importance of mechanotransduction within inflammatory responses, we discuss its capacity for being utilized and harnessed within the context of prevention and rehabilitation of osteoarthritis (OA). Additionally, we introduce a discussion on the Goldilocks zone, which describes the necessity of maintaining a balance of adequate, but not excessive mechanical loading to maintain proper knee joint health. Expanding beyond these, we synthesize findings from current literature that explore the biomechanical loading of various rehabilitation exercises, in hopes of aiding future recommendations for physicians managing KOA and PTOA and athletic training staff strategically planning athlete loads to mitigate the risk of joint injury. The integration of these concepts provides a multifactorial analysis of the contributing factors of KOA and PTOA, in order to spur further research and illuminate the potential of utilizing the body's own physiological responses to mechanical stimuli in the management of OA.

3D Printing Applications for Craniomaxillofacial Reconstruction: A Sweeping Review.

The field of craniomaxillofacial (CMF) surgery is rich in pathological diversity and broad in the ages that it treats. Moreover, the CMF skeleton is a complex confluence of sensory organs and hard and soft tissue with load-bearing demands that can change within millimeters. Computer-aided design (CAD) and additive manufacturing (AM) create extraordinary opportunities to repair the infinite array of craniomaxillofacial defects that exist because of the aforementioned circumstances. 3D printed scaffolds have the potential to serve as a comparable if not superior alternative to the "gold standard" autologous graft. In vitro and in vivo studies continue to investigate the optimal 3D printed scaffold design and composition to foster bone regeneration that is suited to the unique biological and mechanical environment of each CMF defect. Furthermore, 3D printed fixation devices serve as a patient-specific alternative to those that are available off-the-shelf with an opportunity to reduce operative time and optimize fit. Similar benefits have been found to apply to 3D printed anatomical models and surgical guides for preoperative or intraoperative use. Creation and implementation of these devices requires extensive preclinical and clinical research, novel manufacturing capabilities, and strict regulatory oversight. Researchers, manufacturers, CMF surgeons, and the United States Food and Drug Administration (FDA) are working in tandem to further the development of such technology within their respective domains, all with a mutual goal to deliver safe, effective, cost-efficient, and patient-specific CMF care. This manuscript reviews FDA regulatory status, 3D printing techniques, biomaterials, and sterilization procedures suitable for 3D printed devices of the craniomaxillofacial skeleton. It also seeks to discuss recent clinical applications, economic feasibility, and future directions of this novel technology. By reviewing the current state of 3D printing in CMF surgery, we hope to gain a better understanding of its impact and in turn identify opportunities to further the development of patient-specific surgical care.

The Effects of Modified Game Schedules on Injury Rates in the National Hockey League (NHL).

Background Due to the COVID-19 pandemic, many professional sports leagues such as the National Hockey League (NHL) made significant changes to their schedules and operating procedures. Changes included a modified 2019-2020 playoff format, the removal of the 2020-2021 preseason, and condensed game schedules. Though these modifications were made in an effort to protect players from COVID-19, they resulted in decreased training time and preparation. The purpose of this study was to assess the impact of these changes on the rate of player injuries in the NHL both after the resumption of the midseason stoppage and during the subsequent seasons. Hypothesis/purpose Changes to the NHL schedule amid the COVID-19 pandemic resulted in a significant increase in player injury rates. Methods NHL injuries were obtained from an NHL injury database for the 2018-2019 through the 2021-2022 seasons. The date of injury, date of return, injury description, player age, and player position were recorded. Injury rates were calculated as the number of total athlete injuries per 1000 game exposures (GEs). The primary outcome was the injury proportion ratio (IPR) when comparing the injury rates of the post-COVID-19 season with baseline seasons. Secondary measures analyzed injuries based on age, anatomic location, month in the season, position, length of injury, season-ending injuries, and recurring injuries. Results A total of 4604 injuries were recorded between 2018 and 2022. The modified 2019-2020 playoffs had significantly higher rates of injury (IPR = 1.84, 95% confidence interval {CI} = 1.36-2.49) with more game exposures per week. The 2020-2021 season had significantly higher rates of overall player injury compared to baseline seasons (IPR = 1.19, 95% CI = 1.09-1.30) and also had a higher rate of season-ending injuries (IPR = 1.71, 95% CI = 1.38-2.11). Most injuries occurred in the first few months of the 2020-2021 season. There was no significant difference in injury rate based on age group and no significant difference in the average length of injury between seasons. Conclusion Increases in injury rates could be due to decreased offseason training between seasons, the elimination of preseason games, and increased game density. Decreasing typical training timelines and eliminating the preseason to rapidly return to normal competition after unexpected events (pandemics, lockdowns, etc.) may pose a risk to player safety in the NHL. These findings should be considered before future schedule changes in professional hockey.

Hippo Signaling Modulates the Inflammatory Response of Chondrocytes to Mechanical Compressive Loading.

Knee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1ß and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1ß and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA.