Accuracy and completeness of registry-reported unicompartmental knee arthroplasty revision.

INTRODUCTION: The key outcome of joint registries is revision events, which inform clinical practice and identify poor-performing implants. Registries record revision events and reasons, but accuracy may be limited by a lack of standardized definitions of revision. Our study aims to assess the accuracy and completeness of unicompartmental knee arthroplasty (UKA) revision and indications reported to the New Zealand Joint Registry (NZJR) with independent clinical review. METHODS: Case record review of 2272 patients undergoing primary UKA at four large tertiary hospitals between 2000 and 2017 was performed, identifying 158 patients who underwent revision. Detailed review of clinical findings, radiographs and operative data was performed to identify revision cases and the reasons for revision using a standardized protocol. These were compared to NZJR data using chi-squared and Fisher exact tests. RESULTS: The NZJR recorded 150 (95%) of all UKA revisions. Osteoarthritis progression was the most common reason on the systematic clinical review (35%), however, this was underreported to the registry (8%, P < 0.001). A larger proportion of revisions reported to the registry were for 'pain' (30% of cases vs. 5% on clinical review, P < 0.001). A reason for revision was not reported to the registry for 10% of cases. CONCLUSION: The NZJR had good capture of UKA revisions, but had significant differences in registry-reported revision reasons compared to our independent systematic clinical review. These included over-reporting of 'pain', under-reporting of osteoarthritis progression, and failing to identify a revision reason. Efforts to improve registry capture of revision reasons for UKA could be addressed through more standardized definitions of revision and tailored revision options for UKA on registry forms.

Clinical and functional outcomes of TKA after HTO or UKA: a New Zealand Joint Registry Study.

INTRODUCTION: Surgical options for patients with unicompartmental knee osteoarthritis include high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA). When managing younger patients with a higher chance of further surgery, the outcome of any subsequent conversion to total knee arthroplasty (TKA) also needs to be considered. The aim of this study was to compare implant survivorship and patient-reported outcomes for patients undergoing TKA after previous HTO or UKA, with comparisons for age, gender and comorbidities. METHODS: Revision risk and 6-month Oxford Knee Scores (OKS) from the New Zealand Joint Registry were compared for patients who underwent TKA after HTO (HTO-TKA; n = 1556) or UKA (UKA-TKA; n = 965) between 1999 and 2019, with a comparison group of primary TKA (n = 110,948). Mean follow-up was 8.2 years. RESULTS: Adjusted revision risk was similar for HTO-TKA and UKA-TKA groups (hazard ratio (HR) 1.04, p = 0.84); and risk for both groups were higher than primary TKA (HTO-TKA HR 1.45, p = 0.002; UKA-TKA HR 1.51, p = 0.01). Overall adjusted mean OKS at 6 months for HTO-TKA (36.2) was similar to primary TKA (36.8, p = 0.23); and both were higher than UKA-TKA (34.2, p < 0.001). For the youngest patient group (< 55 years), revision rates of UKA-TKA were two-fold higher than HTO-TKA (2.8 vs. 1.3 per 100 component yrs, p < 0.03). HTO-TKA had better OKS (37.5 vs. 34.1, p < 0.0001) for males. Mean OKS for UKA-TKA was lower than HTO-TKA for patients with ASA 1-2 (35.6 vs. 37.5, p < 0.01). CONCLUSION: The findings from this study suggest that revision rate following TKA after HTO and UKA are similar. However, TKA after HTO have superior functional outcomes compared with TKA after UKA and are comparable to functional outcomes post primary TKA. The results support the use of HTO for young, male and less co-morbid patients.

Stimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its poor survival and intense pain at the primary cancer site. Cancer pain is debilitating, contributes to diminished quality of life, and causes opioid tolerance. The stimulator of interferon genes (STING) agonism has been investigated as an anti-cancer strategy. We have developed STINGel, an extended-release formulation that prolongs the availability of STING agonists, which has demonstrated an enhanced anti-tumor effect in OSCC compared to STING agonist injection. This study investigates the impact of intra-tumoral STINGel on OSCC-induced pain using two separate OSCC models and nociceptive behavioral assays. Intra-tumoral STINGel significantly reduced mechanical allodynia in the orofacial cancer model and alleviated thermal and mechanical hyperalgesia in the hind paw model. To determine the cellular signaling cascade contributing to the antinociceptive effect, we performed an in-depth analysis of immune cell populations via single-cell RNA-seq. We demonstrated an increase in M1-like macrophages and N1-like neutrophils after STINGel treatment. The identified regulatory pathways controlled immune response activation, myeloid cell differentiation, and cytoplasmic translation. Functional pathway analysis demonstrated the suppression of translation at neuron synapses and the negative regulation of neuron projection development in M2-like macrophages after STINGel treatment. Importantly, STINGel treatment upregulated TGF-ß pathway signaling between various cell populations and peripheral nervous system (PNS) macrophages and enhanced TGF-ß signaling within the PNS itself. Overall, this study sheds light on the mechanisms underlying STINGel-mediated antinociception and anti-tumorigenic impact.

Innovations in Molecular Biomarkers and Biomaterial-Based Immunotherapies for Head & Neck Cancer.

Purpose of Review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy. Recent Findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease but also have the potential to form immunological memory to prevent future recurrence. Localized controlled-release formulas have further served to reduce toxicity and allow the de-escalation of other treatment modalities. Summary: We review the latest advances in head and neck cancer diagnosis and treatment, including novel molecular biomarkers and immunotherapies.

Nanofibrous MultiDomain Peptide Hydrogels Provide T Cells a 3D, Cytocompatible Environment for Cell Expansion and Antigen-Specific Killing.

T cells have the ability to recognize and kill specific target cells, giving therapies based on their potential for treating infection, diabetes, cancer, and other diseases. However, the advancement of T cell-based treatments has been hindered by difficulties in their ex vivo activation and expansion, the number of cells required for sustained in vivo levels, and preferential localization following systemic delivery. Biomaterials may help to overcome many of these challenges by providing a combined means of proliferation, antigen presentation, and cell localization upon delivery. In this work, we studied self-assembling Multidomain Peptides (MDPs) as scaffolds for T cell culture, activation, and expansion. We evaluated the effect of different MDP chemistries on their biocompatibility with T cells and the maintenance of antigen specificity for T cells cultured in the hydrogels. We also examined the potential application of MDPs as scaffolds for T cell activation and expansion and the effect of MDP encapsulation on T cell phenotype. We found high cell viability when T cells were encapsulated in noncationic MDPs, O5 and D2, and superior retention of antigen specificity and tumor-reactivity were preserved in the anionic MDP, D2. Maintenance of antigen recognition by T cells in D2 hydrogels was confirmed by quantifying immune synapses of T Cells engaged with antigen-presenting cancer cells. When 3D cultured in anionic MDP D2 coloaded with anti-CD3, anti-CD28, IL2, IL7, and IL15, we observed successful T cell proliferation evidenced by upregulation of CD27 and CD107a. This study is the first to investigate the potential of self-assembling peptide-based hydrogels as 3D scaffolds for human T cell applications and demonstrates that MDP hydrogels are a viable platform for enabling T cell in vitro activation, expansion, and maintenance of antigen specificity and therefore a promising tool for future T cell-based therapies.

SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions.

Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiONx coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiONx surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiONx implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiONx implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiONx enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiONx coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiONx coatings to induce in vivo bone regeneration in a challenging oxidative stress environment.

Risk factors for reoperation for arthrofibrosis following primary anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study is to identify the rate and risk factors for a reoperation for arthrofibrosis following primary anterior cruciate ligament (ACL) reconstruction. METHODS: Prospective data recorded in the New Zealand ACL Registry were cross-referenced with data from the Accident Compensation Corporation (ACC). Primary ACL reconstructions performed between April 2014 and May 2021 were analysed. The ACC database was used to identify patients who underwent a reoperation for a diagnosis of arthrofibrosis. Multivariable survival analysis was performed to compute adjusted hazard ratios (aHR) and 95% confidence intervals. RESULTS: A total of 12,296 primary ACL reconstructions were analysed, of which 230 underwent a reoperation for arthrofibrosis (1.9%) at a mean follow-up of 3.6 years. A higher risk of arthrofibrosis was observed in females (aHR = 1.76, p = 0.001), patients with a history of previous knee surgery (aHR = 1.82, p = 0.04) and when a transtibial drilling technique was used (aHR = 1.53, p = 0.03). ACL reconstruction >6 months after injury had the lowest rate of arthrofibrosis (1.3%, aHR = 0.45, p = 0.01). There was no difference in risk between early surgery within 6 weeks versus delayed surgery between 6 weeks and 6 months after injury (2.9% versus 2.1%, aHR = 0.78, not significant). CONCLUSION: Female sex, previous knee surgery and a transtibial drilling technique increased the risk of reoperation for arthrofibrosis. Early surgery within 6 weeks of injury was not associated with an increased risk when compared with surgery between 6 weeks and 6 months after injury. LEVEL OF EVIDENCE: Level III.

Progressive submaximal effort hamstring muscle endurance is reduced after reconstruction of the anterior cruciate ligament.

BACKGROUND: Endurance capability in the muscles controlling the knee is poorly understood post anterior cruciate ligament (ACL) reconstruction, despite many sporting activities requiring notable muscle endurance. The hamstring muscles, when active, provide important anatomical support to protect the reconstructed graft. In the absence of good hamstring endurance, fatigue may predispose individuals to re-injury. OBJECTIVE: To assess whether ACL reconstruction (ACLR) with a hamstring graft leads to reduced hamstring endurance 9-13 months post-surgery. STUDY DESIGN: A cross-sectional inter-limb comparison study was undertaken with participants 9-13 months after an ACLR with a hamstring graft, and a group of age, sex, and activity-matched controls. There were 22 participants in each group. METHOD: Submaximal hamstring endurance was measured using a progressive fatigue test on an isokinetic dynamometer at a joint angular velocity of 120°/second. The dependant variable was the maximum number of repetitions performed. Statistical comparisons were made across injured, uninjured and control group limbs. RESULTS: There was a significant (p < 0.05) deficit in hamstring endurance observed between the injured leg (mean: 111 repetitions, SD 49) and uninjured leg (mean: 136 repetitions, SD 67) of the ACL group, but not between the uninjured and control group legs (mean: 124 repetitions, SD 50). CONCLUSION: The 18% deficit in submaximal hamstring endurance across the ACL-reconstructed individual's limbs is indicative of a notable loss in muscle performance at 9-13 months post-surgery. These results provide initial evidence for supporting further research examining the inclusion of hamstring endurance training in ACL rehabilitation programmes post-surgery.

Human Minor Salivary Glands: A Readily Available Source of Salivary Stem/Progenitor Cells for Regenerative Applications.

Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were developed previously to isolate human stem/progenitor cells (hS/PCs) from major salivary glands (parotid/submandibular). Abundant minor salivary glands located in readily accessible locations in the oral cavity and lip could provide an additional valuable therapeutic resource. An advantage of this cell resource is that these minor glands about the size of grape seeds can be harvested from healthy donors using minimally invasive surgical procedures. The disadvantage of using minor glands is that they contain many fewer cells than do major glands, and thus harvested cells need to be expanded in the lab to create a therapeutic resource. While earlier work has described isolation of proliferative cell populations from minor salivary glands that could be used in regenerative medicine, most of these expanded cells possess properties of mesenchymal cells rather than the epithelial population that secretes salivary products.Here, we describe in detail our recently established methods to isolate and expand hS/PCs isolated from human labial minor salivary glands. Expanded hS/PC populations are epithelial assessed by their expression of epithelial progenitor markers K5 and K14. Like expandable cell populations previously isolated from the major salivary glands, these cells also express nuclear p63, consistent with their ability to be expanded after explant culture. When hS/PCs with these properties are encapsulated into a customized 3D biomimetic hyaluronic acid-based hydrogel, they will assemble into microstructures that retain some progenitor markers while also beginning to differentiate. The increased expression of secreted mucin MUC-7 was used to demonstrate differentiation and secretory potential in assembled hS/PC microstructures. Compared to hS/PCs from major glands, those from minor salivary glands tend to be more heterogeneous in early passage; thus, use of K5/K14/p63 as an early quality assessment tool is highly recommended. Additionally, hS/PCs from minor glands are sensitive to stress and if mishandled will demonstrate a stress response that leads to their transitioning to a flat, squamous cell-like appearance that is of limited utility in regenerative medicine applications. We conclude that properly handled hS/PCs from minor salivary glands represent a powerful new source of therapeutic cells for applications including treating patients with chronic xerostomia.

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.

Implant Survival in Tissue-Engineered Mandibular Reconstruction-Early Experiences.

Study Design: This article is to evaluate the early outcomes of dental implants placed in bone generated with tissueengineering techniques, specifically recombinant human bone morphogenic protein-2 (rhBMP-2), allogeneicbone particulate, and bone marrow aspirate concentrate (BMAC) in patients with resection of benignpathology. Objective: To evaluate the long-term prognosis of dental implants placed in tissue engineered mandibular reconstruction. Methods: We retrospectively evaluated 12 patient records, all of whom underwent segmental mandibular resection of benign pathology and reconstruction with a combination of BMAC, rhBMP-2, and allogeneic bone. Collecteddata points included the patient's age, gender, medical and social histories, implant site and placement date, resection/reconstruction date, final prosthesis, pathology resected, and follow-up dates (average 25 monthsof follow-up). Implant success was defined as clinical osseointegration (immobility), absence of peri-implantradiolucency, and absence of infection. Results: Twelve patients met inclusion criteria with a total of 46 implants. The overall implant survival rate was 91.3%. There were 4 implant failures occurring in two patients: 1 failure in Patient 3 and 3 failures in Patient 8. Neitherpatient had any existing medical comorbidities or social history known to increase the risk for implant failure. The average implant placement occurred 11.6 months after mandibular reconstruction. Conclusions: Preliminary findings of implant placement in bone generated with tissue engineering techniques have shown to be another predictable alternative for orofacial rehabilitation. Practical Implications: Dental rehabilitationusing dental implants is a predictable treatment option for patients that have required reconstruction of largebony defects status post resection of benign pathology using novel tissue engineering techniques.

Identification of preclinical dementia according to ATN classification for stratified trial recruitment: A machine learning approach.

INTRODUCTION: The Amyloid/Tau/Neurodegeneration (ATN) framework was proposed to identify the preclinical biological state of Alzheimer's disease (AD). We investigated whether ATN phenotype can be predicted using routinely collected research cohort data. METHODS: 927 EPAD LCS cohort participants free of dementia or Mild Cognitive Impairment were separated into 5 ATN categories. We used machine learning (ML) methods to identify a set of significant features separating each neurodegeneration-related group from controls (A-T-(N)-). Random Forest and linear-kernel SVM with stratified 5-fold cross validations were used to optimize model whose performance was then tested in the ADNI database. RESULTS: Our optimal results outperformed ATN cross-validated logistic regression models by between 2.2% and 8.3%. The optimal feature sets were not consistent across the 4 models with the AD pathologic change vs controls set differing the most from the rest. Because of that we have identified a subset of 10 features that yield results very close or identical to the optimal. DISCUSSION: Our study demonstrates the gains offered by ML in generating ATN risk prediction over logistic regression models among pre-dementia individuals.

Intraosseous regional prophylaxis in total knee arthroplasty.

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date.

Comparison of Knee Pain and Difficulty With Kneeling Between Patellar Tendon and Hamstring Tendon Autografts After Anterior Cruciate Ligament Reconstruction: A Study From the New Zealand ACL Registry.

BACKGROUND: The bone-patellar tendon-bone (BTB) autograft is associated with difficulty with kneeling after anterior cruciate ligament (ACL) reconstruction; however, it is unclear whether it results in a more painful or symptomatic knee compared with the hamstring tendon autograft. PURPOSE: To identify the rate and risk factors for knee pain and difficulty with kneeling after ACL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Primary ACL reconstruction procedures prospectively recorded in the New Zealand ACL Registry from April 2014 to May 2021 were analyzed. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to identify patients reporting consequential knee pain (CKP), defined as a KOOS Pain subscore of ≤72 points, and severe kneeling difficulty (SKD), defined as a self-report of "severe" or "extreme" difficulty with kneeling. Absolute values of the KOOS Pain and Symptoms subscales were also compared. RESULTS: A total of 10,999 patients were analyzed. At 2-year follow-up, 9.3% (420/4492) reported CKP, and 12.0% (537/4471) reported SKD. The most important predictor of CKP at 2-year follow-up was having significant pain before surgery (adjusted odds ratio, 4.10; P < .001). The most important predictor of SKD at 2-year follow-up was the use of a BTB autograft rather than a hamstring tendon autograft (21.3% vs 9.4%, respectively; adjusted odds ratio, 3.12; P < .001). There was no difference between the BTB and hamstring tendon grafts in terms of CKP (9.9% vs 9.2%, respectively; P = .494) or in absolute values of the KOOS Pain (mean, 88.7 vs 89.0, respectively; P = .37) and KOOS Symptoms (mean, 82.5 vs 82.1, respectively; P = .49) subscales. CONCLUSION: At 2-year follow-up after primary ACL reconstruction, 9.3% of patients reported CKP, and 12.0% reported SKD. The BTB autograft was associated with difficulty with kneeling, but it did not result in a more painful or symptomatic knee compared with the hamstring tendon autograft.

Does Immediate Long-Span Nerve Allograft Reconstruction Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection for Benign and Malignant Disease.

BACKGROUND: Peripheral nerve injury can lead to chronic postsurgical pain (CPSP) and neuropathic pain following major surgery. PURPOSE: Determine in patients undergoing ablative mandibular operations with transection of the trigeminal nerve: do those who undergo immediate repair, when compared to those whose nerves are not repaired, have a decreased or increased risk for CPSP or post-traumatic trigeminal neuropathic pain (PTTNp)? STUDY DESIGN, SETTING, SAMPLE: A multisite, retrospective cohort of patients who underwent resection of the mandible for benign or malignant disease with either no repair or immediate repair of the intentionally transected trigeminal nerve with a long-span nerve allograft were analyzed for the presence or absence of CPSP and PTTNp at 6 months. PREDICTOR VARIABLE: The primary predictor was the immediate repair or no repair of the trigeminal nerve. MAIN OUTCOME VARIABLE: The primary outcome was the presence or absence of CPSP and PTTNp at 6 months postsurgery. COVARIATES: There were 13 covariate variables, including age, sex, ethnicity, nerve injury, type of PTTNp, malignant or benign pathology and subtypes of each, use of radiation or chemotherapy, treatment of transected nerve end, longest follow-up time, pain scale, and onset of pain. ANALYSES: Two-tailed Student's t test and Welch's t test were performed on mean scores and post hoc logistics and linear regression modeling were performed when indicated. The confidence level for statistical significance was P value <.05. RESULTS: There were 103 and 94 subjects in the immediate and no-repair groups, respectively. The incidence of CPSP in the no-repair group was 22.3% and PTTNp was 2.12%, while there was 3.8% CPSP and 0% PTTNp in the repair group, which was statistically significant (P = <.001). Logistic regression modeling showed a statistically significant inverse relationship between the immediate repair and the incidence of CPSP/PTTNp with an odds ratio of 0.43, 95% confidence interval 0.18 to 1.01, P = .05. Greater age, malignant pathology, and chemo/radiation treatments were covariates found more frequently in the no repair group. CONCLUSION AND RELEVANCE: Immediate repair of an intentionally transected trigeminal nerve with a long-span nerve allograft during resection of the mandible for both benign and malignant disease appears to reduce CPSP and possibly eliminate the development of PTTNp.

Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects.

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

Better post-operative outcomes at 1-year follow-up are associated with lower levels of pre-operative synovitis and higher levels of IL-6 and VEGFA in unicompartmental knee arthroplasty patients.

PURPOSE: Osteoarthritis (OA) is associated with inflammation, and residual inflammation may influence outcomes following knee arthroplasty. This may be more relevant for patients undergoing unicompartmental knee arthroplasty (UKA) due to larger remaining areas of native tissue. This study aimed to: (1) characterise inflammatory profiles for medial UKA patients and (2) investigate whether inflammation markers are associated with post-operative outcomes. METHODS: This prospective, observational study has national ethics approval. Bloods, synovial fluid, tibial plateaus and synovium were collected from medial UKA patients in between 1 January 2021 and 31 December 2021. Cytokine and chemokine concentrations in serum and synovial fluid (SF) were measured with multiplexed assays. Disease severity of cartilage and synovium was assessed using validated histological scores. Post-operative outcomes were measured with Oxford Knee Score (OKS), Forgotten Joint Score (FJS-12) and pain scores. RESULTS: The study included 35 patients. SF VEGFA was negatively correlated with pre-operative pain at rest (r - 0.5, p = 0.007), and FJS-12 at six-week (r 0.44, p = 0.02), six-month (r 0.61, p < 0.01) and one-year follow-up (r 0.63, p = 0.03). Serum and SF IL-6 were positively correlated with OKS at early follow-up (serum 6 weeks, r 0.39, p = 0.03; 6 months, r 0.48, p < 0.01; SF 6 weeks, r 0.35, p = 0.04). At six weeks, increased synovitis was negatively correlated with improvements in pain at rest (r - 0.41, p = 0.03) and with mobilisation (r - 0.37, p = 0.047). CONCLUSION: Lower levels of synovitis and higher levels of IL-6 and VEGFA were associated with better post-operative outcomes after UKA, which could be helpful for identifying UKA patients in clinical practice. LEVEL OF EVIDENCE: Level IV case series.

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing for Craniomaxillofacial Bone Regeneration.

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as ß-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific structures. More importantly, it has enabled the production of biomimetic scaffolds with porous structures that mimic the natural extracellular matrix while allowing for cell growth-a critical factor in determining the overall success of the BTR modality. While the concept of 3DP bioceramic bone tissue scaffolds for human applications is nascent, numerous studies have highlighted its potential in restoring both form and function of critically sized defects in a wide variety of translational models. In this review, we summarize these recent advancements and present a review of the engineering principles and methodologies that are vital for using 3DP technology for craniomaxillofacial reconstructive applications. Moreover, we highlight future advances in the field of dynamic 3D printed constructs via shape-memory effect, and comment on pharmacological manipulation and bioactive molecules required to treat a wider range of boney defects.