Skin serves as the first-order protective barrier against the environment and any significant disruptions in skin integrity must be promptly restored. Despite significant advances in therapeutic strategies, effective management of large chronic skin wounds remains a clinical challenge. Dermal fibroblasts are the primary cell type responsible for remodeling the extracellular matrix (ECM) in wound healing.
View Article and Find Full Text PDFNuclear morphology, which modulates chromatin architecture, plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored, yet is especially crucial for cell-based therapies. In this study, we fabricated implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell paracrine signaling for osteogenesis and cranial bone regeneration.
View Article and Find Full Text PDFEffective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs).
View Article and Find Full Text PDFBeyond the surgeon's feedback on bone behavior in the operating room, there is a paucity of data present in the literature on the mechanical properties of pediatric calvarial bone. The present study tested the calvarial bone of four species (Adult Humans, Dog, Pig, and Monkey) to find the mechanical properties. Three types of tests were performed; flexural, compression, and torsion to mimic how bone is handled during the surgery and the results were further compared with the existing published data for human pediatric calvarium.
View Article and Find Full Text PDFBallistic facial trauma can cause complex fractures and overlying soft tissue damage, with a zone of injury that extends beyond the bullet tract. Early skeletal fixation is indicated, and previous large case series describe the use of debrided bone fragments as 'spare part' grafts. This series presents the indications and techniques for simultaneous coronoid bone grafting in 2 patients who sustained a gunshot wound to the right midface and required coronoidectomy.
View Article and Find Full Text PDFRecombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production.
View Article and Find Full Text PDFApproaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation.
View Article and Find Full Text PDFComposite cranial defects have individual functional and aesthetic ramifications, as well as societal burden, while posing significant challenges for reconstructive surgeons. Single-stage composite reconstruction of these deformities entail complex surgeries that bear many short- and long-term risks and complications. Current research on composite scalp-cranial defects is sparse and one-dimensional, often focusing solely on bone or skin.
View Article and Find Full Text PDFThe evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths.
View Article and Find Full Text PDFEffective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed cells for bone tissue engineering. As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat, MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.
View Article and Find Full Text PDFUnilateral condylar hyperplasia (UCH) results in facial asymmetry, malocclusion, and temporomandibular joint dysfunction. Treatment consists of both surgical and orthodontic intervention. A review was performed for 4 patients with UCH who underwent digital surgical planning (DSP)-assisted condylectomy.
View Article and Find Full Text PDFWnt signaling plays a major role in regulating cell proliferation and differentiation. The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either through β-catenin in the canonical pathway or through a series of other proteins in the noncanonical pathway. Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body, establishing the complex interplay between Wnt signaling and other signaling pathways.
View Article and Find Full Text PDFOvarian cancer (OC) is one of the most lethal malignancies of the female reproductive system. OC patients are usually diagnosed at advanced stages due to the lack of early diagnosis. The standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy, while several targeted therapies have recently been approved for maintenance treatment.
View Article and Find Full Text PDFCraniosynostosis is a condition with neurologic and aesthetic sequelae requiring invasive surgery. Understanding its pathobiology requires familiarity with the processes underlying physiologic suture closure. Animal studies have shown that cyclical strain from chewing and suckling influences the closure of cranial vault sutures, especially the metopic, an important locus of craniosynostosis.
View Article and Find Full Text PDFTopographical cues on cells can, through contact guidance, alter cellular plasticity and accelerate the regeneration of cultured tissue. Here we show how changes in the nuclear and cellular morphologies of human mesenchymal stromal cells induced by micropillar patterns via contact guidance influence the conformation of the cells' chromatin and their osteogenic differentiation in vitro and in vivo. The micropillars impacted nuclear architecture, lamin A/C multimerization and 3D chromatin conformation, and the ensuing transcriptional reprogramming enhanced the cells' responsiveness to osteogenic differentiation factors and decreased their plasticity and off-target differentiation.
View Article and Find Full Text PDFBackground: Genetic research in nonsyndromic craniosynostosis remains limited compared with syndromic craniosynostosis. This systematic review aimed to comprehensively summarize the genetic literature of nonsyndromic craniosynostosis and highlight key signaling pathways.
Methods: The authors performed a systematic literature search of PubMed, Ovid, and Google Scholar databases from inception until December of 2021 using search terms related to nonsyndromic craniosynostosis and genetics.