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Objective The current study investigated the influence of the coronavirus (COVID-19) pandemic on patients with congenital craniofacial diagnoses.Methods Patients (n = 66) with craniofacial diagnoses aged between 8 and 17 were prospectively evaluated with longitudinal psychosocial assessments using the anger, anxiety, depressive symptoms, and peer relationships instruments within the pediatric Patient-Reported Outcomes Measurement Information System (PROMIS). The COVID-19 cohort (n = 33) included patients with assessments within 2 years prior to the pandemic (t0) and during the pandemic (t1; March 2020 to March 2021). An age-matched comparison cohort (n = 33) with similar demographics and diagnoses included patients assessed twice over 3 years prior to the pandemic.Results All PROMIS measures were in the average range clinically for both groups across time points. However, the COVID-19 group reported a significant increase in depressive symptoms during the pandemic (t1) compared to pre-pandemic (t0) scores (48.2 ± 10.1 vs 44.3 ± 9.4, P= .04, d= −0.37), while the comparison group did not demonstrate any differences in psychosocial functioning between t0 and t1. For the COVID-19 cohort, only the pandemic timeframe (r= 0.21, P= .03) was significantly associated with increased depressive symptom scores, and no other sociodemographic or medical variables were associated with depressive symptoms.Conclusions Self-reported depressive symptoms increased during the COVID-19 pandemic in patients with congenital craniofacial diagnoses. Longitudinal studies are needed to elucidate whether such changes will be persistent or compound known variables associated with psychosocial functioning.

Objective To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG).Design Retrospective review.Setting Tertiary level craniofacial clinic.Participants 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022.Interventions ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System.Main Outcome Measures Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG.Results Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (β=0.36, p = 0.01) and higher pain scores (β=0.39, p = 0.02), but not length of hospital stay.Conclusions We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

Objective To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMPDesign Retrospective case seriesSetting Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CAPatients/Participants Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included.Interventions BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask.Main Outcome Measures We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion.Results Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%).Conclusions This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

Cells are known to perceive their microenvironment through extracellular and intracellular mechanical signals. Upon sensing mechanical stimuli, cells can initiate various downstream signaling pathways that are vital to regulating proliferation, growth, and homeostasis. One such physiologic activity modulated by mechanical stimuli is osteogenic differentiation. The process of osteogenic mechanotransduction is regulated by numerous calcium ion channels—including channels coupled to cilia, mechanosensitive and voltage‐sensitive channels, and channels associated with the endoplasmic reticulum. Evidence suggests these channels are implicated in osteogenic pathways such as the YAP/TAZ and canonical Wnt pathways. This review aims to describe the involvement of calcium channels in regulating osteogenic differentiation in response to mechanical loading and characterize the fashion in which those channels directly or indirectly mediate this process. The mechanotransduction pathway is a promising target for the development of regenerative materials for clinical applications due to its independence from exogenous growth factor supplementation. As such, also described are examples of osteogenic biomaterial strategies that involve the discussed calcium ion channels, calcium‐dependent cellular structures, or calcium ion‐regulating cellular features. Understanding the distinct ways calcium channels and signaling regulate these processes may uncover potential targets for advancing biomaterials with regenerative osteogenic capabilities. This work summarizes notable calcium channels that regulate mechanotransduction signaling pathways and their relevance in skeletal biomaterial design. The various calcium channels, structures, and associated pathways that are relevant to osteogenic differentiation and regeneration are thus discussed in this review. Ultimately, the purpose of this work is to inform the next generation of biomaterial development through calcium centered strategies.

The temporospatial equilibrium of phosphate contributes to physiological bone development and fracture healing, yet optimal control of phosphate content has not been explored in skeletal regenerative materials. Nanoparticulate mineralized collagen glycosaminoglycan (MC‐GAG) is a synthetic, tunable material that promotes in vivo skull regeneration. In this work, the effects of MC‐GAG phosphate content on the surrounding microenvironment and osteoprogenitor differentiation are investigated. This study finds that MC‐GAG exhibits a temporal relationship with soluble phosphate with elution early in culture shifting to absorption with or without differentiating primary bone marrow‐derived human mesenchymal stem cells (hMSCs). The intrinsic phosphate content of MC‐GAG is sufficient to stimulate osteogenic differentiation of hMSCs in basal growth media without the addition of exogenous phosphate in a manner that can be severely reduced, but not eliminated, by knockdown of the sodium phosphate transporters PiT‐1 or PiT‐2. The contributions of PiT‐1 and PiT‐2 to MC‐GAG‐mediated osteogenesis are nonredundant but also nonadditive, suggestive that the heterodimeric form is essential to its activity. These findings indicate that the mineral content of MC‐GAG alters phosphate concentrations within a local microenvironment resulting in osteogenic differentiation of progenitor cells via both PiT‐1 and PiT‐2. Dynamic phosphate fluxes influence physiological bone development and healing; however, temporospatial phosphate control has not been explored in skeletal regenerative materials. This work describes the microenvironmental changes in phosphate equilibrium induced by a nanoparticulate mineralized collagen glycosaminoglycan material (MC‐GAG). The function of phosphate intrinsic to MC‐GAG in promoting osteoprogenitor differentiation via sodium phosphate cotransporters, PiT‐1 and PiT‐2, is characterized.

Custom synthesis of extracellular matrix (ECM)-inspired materials for condition-specific reconstruction has emerged as a potentially translatable regenerative strategy. In skull defect reconstruction, nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) have demonstrated osteogenic and anti-osteoclastogenic properties, culminating in the ability to partially heal in vivoskull defects without the addition of exogenous growth factors or progenitor cell loading. In an effort to reduce catabolism during early skull regeneration, we fabricated a composite material (MCGO) of MC-GAG and recombinant osteoprotegerin (OPG), an endogenous anti-osteoclastogenic decoy receptor. In the presence of differentiating osteoprogenitors, MCGO demonstrated an additive effect with endogenous OPG limited to the first 14 days of culture with total eluted and scaffold-bound OPG exceeding that of MC-GAG. Functionally, MCGO exhibited similar osteogenic properties as MC-GAG, however, MCGO significantly reduced maturation and resorptive activities of primary human osteoclasts. In a rabbit skull defect model, MCGO scaffold-reconstructed defects displayed higher mineralization as well as increased hardness and microfracture resistance compared to non-OPG functionalized MC-GAG scaffolds. The current work suggests that MCGO is a development in the goal of reaching a materials-based strategy for skull regeneration.