Faculty Bibliography

Little is known about patients' and families' lived experiences of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients' and caregivers' perceptions and experiences of social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to (1) provide an overview of existing literature, (2) identify gaps and areas for further research, and (3) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. Four themes emerged, including (1) weighing risks and benefits (2) timing of GT trial participation, (3) value of clear communication, and (4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT-their understanding of its safety, efficacy, and risks-rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations' efforts to develop educational materials tailored to patients' and families' expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.

BACKGROUND:Commercial payer-negotiated rates for cleft lip and palate surgery have not been evaluated on a national scale. The aim of this study was to characterize commercial rates for cleft care, both in terms of nationwide variation and in relation to Medicaid rates. METHODS:A cross-sectional analysis was performed of 2021 hospital pricing data from Turquoise Health, a data service platform that aggregates hospital price disclosures. The data were queried by CPT code to identify 20 cleft surgical services. Within- and across-hospital ratios were calculated per CPT code to quantify commercial rate variation. Generalized linear models were used to assess the relationship between median commercial rate and facility-level variables and between commercial and Medicaid rates. RESULTS:There were 80,710 unique commercial rates from 792 hospitals. Within-hospital ratios for commercial rates ranged from 2.0 to 2.9 and across-hospital ratios ranged from 5.4 to 13.7. Median commercial rates per facility were higher than Medicaid rates for primary cleft lip and palate repair ($5492.20 versus $1739.00), secondary cleft lip and palate repair ($5429.10 versus $1917.00), and cleft rhinoplasty ($6001.00 versus $1917.00; P < 0.001). Lower commercial rates were associated with hospitals that were smaller ( P < 0.001), safety-net ( P < 0.001), and nonprofit ( P < 0.001). Medicaid rate was positively associated with commercial rate ( P < 0.001). CONCLUSIONS:Commercial rates for cleft surgical care demonstrated marked variation within and across hospitals, and were lower for small, safety-net, or nonprofit hospitals. Lower Medicaid rates were not associated with higher commercial rates, suggesting that hospitals did not use cost-shifting to compensate for budget shortfalls resulting from poor Medicaid reimbursement.

Non-resorbable dental barrier membranes entail the risk of dehiscence due to their smooth and functionally inert surfaces. Non-thermal plasma (NTP) treatment has been shown to increase the hydrophilicity of a biomaterials and could thereby enhance cellular adhesion. This study aimed to elucidate the role of allyl alcohol NTP treatment of poly(tetrafluoroethylene) in its cellular adhesion. The materials (non-treated PTFE membranes (NTMem) and NTP-treated PTFE membranes (PTMem)) were subjected to characterization using scanning electron microscopy (SEM), contact angle measurements, X-ray photoelectron spectroscopy (XPS), and electron spectroscopy for chemical analysis (ESCA). Cells were seeded upon the different membranes, and cellular adhesion was analyzed qualitatively and quantitatively using fluorescence labeling and a hemocytometer, respectively. PTMem exhibited higher surface energies and the incorporation of reactive functional groups. NTP altered the surface topography and chemistry of PTFE membranes, as seen through SEM, XPS and ESCA, with partial defluorination and polymer chain breakage. Fluorescence labeling indicated significantly higher cell populations on PTMem relative to its untreated counterparts (NTMem). The results of this study support the potential applicability of allyl alcohol NTP treatment for polymeric biomaterials such as PTFE-to increase cellular adhesion for use as dental barrier membranes.

Bone tissue regeneration is a complex process that proceeds along the well-established wound healing pathway of hemostasis, inflammation, proliferation, and remodeling. Recently, tissue engineering efforts have focused on the application of biological and technological principles for the development of soft and hard tissue substitutes. Aim is directed towards boosting pathways of the healing process to restore form and function of tissue deficits. Continued development of synthetic scaffolds, cell therapies, and signaling biomolecules seeks to minimize the need for autografting. Despite being the current gold standard treatment, it is limited by donor sites' size and shape, as well as donor site morbidity. Since the advent of computer-aided design/computer-aided manufacturing (CAD/CAM) and additive manufacturing (AM) techniques (3D printing), bioengineering has expanded markedly while continuing to present innovative approaches to oral and craniofacial skeletal reconstruction. Prime examples include customizable, high-strength, load bearing, bioactive ceramic scaffolds. Porous macro- and micro-architecture along with the surface topography of 3D printed scaffolds favors osteoconduction and vascular in-growth, as well as the incorporation of stem and/or other osteoprogenitor cells and growth factors. This includes platelet concentrates (PCs), bone morphogenetic proteins (BMPs), and some pharmacological agents, such as dipyridamole (DIPY), an adenosine A 2A receptor indirect agonist that enhances osteogenic and osteoinductive capacity, thus improving bone formation. This two-part review commences by presenting current biological and engineering principles of bone regeneration utilized to produce 3D-printed ceramic scaffolds with the goal to create a viable alternative to autografts for craniofacial skeleton reconstruction. Part II comprehensively examines recent preclinical data to elucidate the potential clinical translation of such 3D-printed ceramic scaffolds.

Collagen, an abundant extracellular matrix protein, has shown hemostatic, chemotactic, and cell adhesive characteristics, making it an attractive choice for the fabrication of tissue engineering scaffolds. The aim of this study was to synthesize a fibrillar colloidal gel from Type 1 bovine collagen, as well as three dimensionally (3D) print scaffolds with engineered pore architectures. 3D-printed scaffolds were also subjected to post-processing through chemical crosslinking (in N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide) and lyophilization. The scaffolds were physicochemically characterized through Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis, Differential Scanning Calorimetry, and mechanical (tensile) testing. In vitro experiments using Presto Blue and Alkaline Phosphatase assays were conducted to assess cellular viability and the scaffolds' ability to promote cellular proliferation and differentiation. Rheological analysis indicated shear thinning capabilities in the collagen gels. Crosslinked and lyophilized 3D-printed scaffolds were thermally stable at 37 °C and did not show signs of denaturation, although crosslinking resulted in poor mechanical strength. PB and ALP assays showed no signs of cytotoxicity as a result of crosslinking. Fibrillar collagen was successfully formulated into a colloidal gel for extrusion through a direct inkjet writing printer. 3D-printed scaffolds promoted cellular attachment and proliferation, making them a promising material for customized, patient-specific tissue regenerative applications.

OBJECTIVE:Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA. METHODS:PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue. RESULTS:Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient. CONCLUSION/CONCLUSIONS:NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored.

BACKGROUND:Pressure injury (PI) development is multifactorial. In patients with dark skin tones, identifying impending PIs by visual skin assessment can be especially challenging. The need for improved skin assessment techniques, especially for persons with dark skin tones, continues to increase. Similarly, greater awareness of the need for inclusivity with regard to representation of diverse skin colors/tones in education materials is apparent. OBJECTIVE:To provide current perspectives from the literature surrounding skin assessment and PI development in patients with dark skin tones. METHODS:The following elements will be discussed through the lens of skin tone: (1) historical perspectives of PI staging from the National Pressure Injury Advisory Panel, (2) epidemiology of PI, (3) anatomy and physiology of the skin, (3) skin tone assessment and measurement, (4) augmented visual assessment modalities, (5) PI prevention, (6) PI healing, (7) social determinants of health, and (8) gaps in clinician education. CONCLUSIONS:This article highlights the gap in our clinical knowledge regarding PIs in patients with dark skin tones. Racial disparities with regard to PI development and healing are especially clear among patients with dark skin tones. Skin tone color assessment must be standardized and quantifiable in clinical education, practice, and research. This work is urgently needed, and support from private and governmental agencies is essential.