Ziyad Samir Haidar

The growing global demand for safe, effective, and sustainable bone regeneration materials is accelerating the search for innovative alternatives to conventional grafts. Trans-forming fishery by-products into high-performance biomaterials offers a unique opportunity to address both clinical needs and environmental sustainability. In two previous studies, we developed a nano-hydroxyapatite biomaterial (nanoS-HAp) from Chilean salmon (Salmo salar) backbone waste using a modified, simplified, and cost-effective alkaline hydrolysis–calcination method. This sustainable process produced a highly crystal-line, Ca/P-balanced, nano-structured material with excellent physico-chemico-mechanical properties and superior in vitro biocompatibility and osteoconductivity compared to widely used synthetic and xenogeneic hydroxyapatites. Building on these findings, the present study provides the first in vivo evaluation of our salmon-derived hydroxyapatite (SAHA). A critical-sized, non-vascularized calvarial defect model was established in 21 Sprague Dawley rats, with systemic safety and local de novo bone regeneration assessed at 15-, 30-, and 60-days post-implantation. Hematological and biochemical profiles showed no significant deviations from control values, while radiographic and histological anal-yses revealed enhanced bone callus formation and defect closure, with outcomes comparable to leading commercial bovine and human grafts. These results confirm the biocompatibility, osteogenic efficacy, and cost-friendly potential of SAHA in vivo. By transforming fishery waste into a high-performance and implantable HAp, this malleable material represents a promising and sustainable alternative for bone regeneration and repair.

The need for effective and safe approaches to promote tissue restoration, repair, replacement, and regeneration has spurred interest in biofunctional materials, including copper and microvesicles, giv...

Bone development and growth Bone development and growth, briefly, is governed by the process of osteogenesis and occur through two distinct mechanisms: intramembranous ossification and endochondral ossification [1]. Both pathways are essential for skeletal formation during embryonic development, postnatal growth, and bone repair throughout life, though they differ in their cellular pathways and developmental contexts [1, 2]. Intramembranous ossification involves the direct differentiation of mesenchymal stem cells into osteoblasts, bypassing a cartilage intermediate. This process is primarily responsible for forming flat bones, such as the skull, clavicle, and parts of the pelvis. Mesenchymal cells condense into membranous structures, differentiate into osteoblasts, and secrete the bone matrix, facilitating rapid mineralization essential for skeletal development. Endochondral ossification, in contrast, relies on a cartilage intermediate that is gradually replaced by bone. Responsible for forming most long bones, including the limbs, spine, and ribcage, this process begins with a cartilage model that undergoes hypertrophy, vascular invasion, and subsequent replacement by bone tissue. This mechanism enables bone growth and elongation during childhood and adolescence, remodeling cartilage into mature bone. Both ossification processes are regulated by intricate pathway signaling networks that coordinate the differentiation, proliferation, and activity of bone-forming and cartilage-forming cells [1]. Key pathways include the following:

Accurate diagnosis is fundamental to effective healthcare, guiding clinical and surgical decisions and ultimately influencing treatment outcomes and prognosis. Recent advancements in nanomaterials and...

The landscape of cancer therapeutics has undergone a transformative shift from broad approaches, such as radiation and chemotherapy, to more precise strategies, encompassing small molecule kinase inhibitors and monoclonal antibodies targeting immune checkpoint molecules. Oncolytic viruses (OVs) have recently emerged as a promising and viable option for cancer immunotherapy, particularly for “cold” tumors entrenched in an immunologically-suppressive tumor microenvironment. Genetic attenuation refines the characteristics of OVs, replacing specific genes to enhance conditional viral replication within tumor cells. Despite their potential, the therapeutic use of OVs faces challenges such as pre-mature elimination by the immune system of the host alongside the dense stromal barriers. In this review article, the strategic encapsulation of genetically-engineered OVs within intra-lesional/-tumoral carriers/ vehicles such as mesenchymal stem cells are explored. To further enhance vector delivery strategies and precise targeting, protecting/shielding OVs from host immune responses, via utilizing release-controlled nanoparticles and employing nanofilaments to optimize vector propagation, for example, are discussed. Such innovative approaches not only mitigate challenges related to pre-mature viral clearance and stromal barriers yet also facilitates a localized, controlled, and sustained release of OVs, thereby optimizing their therapeutic bio-safety and -impact. Ongoing clinical investigations are exploring the synergies between OVs and carriers/delivery systems, combined with various anti-cancer therapeutics as radiotherapy, chemotherapy, immune checkpoint inhibitors, and monoclonal antibodies. These studies hold promise for revolutionizing cancer treatment, ensuring both safety and efficacy, aiming to advance bio-pharmaceutical delivery systems from bench-top to bed-side for enhanced therapeutic results, improved patient survival, and enhanced quality of life or QoL.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods—alkaline hydrolysis, calcination, and NaOH hydrolysis—to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis–calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

Salmon aquaculture generates a substantial volume of waste material, offering potential for biomaterial production. This industry produces significant waste, which can be repurposed for various biological applications, particularly in biomaterial production for tissue engineering with pertinent applications in osteo-conduction, osteo-induction, and clinical/surgical bone regeneration and repair. The process involves a standardized pre-treatment stage aimed at minimizing biological waste content. Subsequently, the treatment stage, contingent on the chosen methodology, facilitates the removal of proteins, lipids, molecules, and other compounds, leaving the mineral phase as a valuable substrate. The selection of the optimal method, whether alkaline hydrolysis, calcination, or NaOH hydrolysis, for obtaining this substrate necessitates thorough examination through chemical, physical, and biological assessments, including Raman Spectroscopy and X-Ray Diffraction. This study aims to identify the most efficient laboratory process for biofunctional nano-sized hydroxyapatite mineral production derived from Chilean salmon fish backbone waste.

Tooth loss can cause functional impairment, in terms of chewing/mastication ability and choice of foods/diet, leading to malnutrition, which might ultimately impact general health and well-being. No studies on homocysteine (Hcy), an inflammatory sulfur-containing amino acid biomarker, levels, and tooth loss (or number of remaining teeth), are present. This study opted to obtain data from the available National Health and Nutrition Examination Survey III (NHANES III) and perform statistical analysis to investigate the association between tooth loss and tHcy (plasma/serum levels), with a focus on the elderly population. Acquired data for 1568 individuals aged 65 years or older were then tabulated, to detail. Age, gender, cholesterol, income, education, exercise, creatinine, systolic blood pressure, body mass index, and dental state were each found to be independently associated with tHcy. In a multiple regression model, only age (ρ0.0001), education (ρ0.0001), creatinine (ρ0.0001), and dental state (ρ0.003) were significantly associated with tHcy, explaining 22% of the variation detected in log-[tHcy]. Plasma Hcy levels in patients are associated with dental status and can be notably affected with oro-dental health, socioeconomic status, and access to therapeutic interventions. Considering these findings, tHcy level monitoring (to diagnose vitamin B6, B9/folate/folic acid or B12 deficiency) as well as nutritional counseling and vitamin supplementation (rechecked post-8 weeks) should be considered and incorporated into the diagnostic and treatment plan for the edentate/edentulous elders, especially if other cardiovascular or inflammatory risk factors are present. In the context of osteogenesis and oral health, research exploring the relationship between elevated Hcy levels and alveolar bone, and tooth loss can provide valuable insights into the underlying mechanisms of bone metabolism and dental health. Understanding how Hcy levels impact bone density, bone remodeling processes, and periodontal health can potentially lead to the design, innovation, development, and translation of novel therapeutic approaches and preventive strategies for osteoporosis, periodontal disease, as well as tooth loss.

HHT/OWRS is a very rare, hereditary, genetic autosomal-dominant disorder characterized by local angiodysplasias on skin and mucosae, even more rarely reported in the oral and dental health-related literature. It affects blood vessel formation throughout the body and is often accompanied with recurrent and severe episodes of epistaxis and telangiectasia on the skin and mucous membranes, including oral mucosae; and henceforth, perhaps the first sign of OWRS/HHT that can be initially diagnosed is by us, dentists/odontologists, oral and cranio-maxillo-facial surgeons, and specialized oral, dental, head, face and neck health care providers. Such symptoms may be associated with an IgA deficiency and, rarely, with von Willebrand disease. Thus, we are in an optimal position to detect the OWRS/HHT symptoms early, even if symptoms of other conditions may or do mimic OWRS/HHT oral lesions. Herein, this chapter re-visits and reviews, for the interested clinician, surgeon, scientist, researcher, and Innovation in Osteogenesis Research reader, the current knowledge on a very rare yet complex disease. Hence, the aim herein is for it to serve as a reminder as well as a contemporary clinical and surgical guide aiding in detecting, diagnosing, understanding, and efficaciously managing (including Health Care Information Management) patients suffering from OWRS or HHT.

Introduction: Given the ensuing increase in bone and periodontal diseases and defects, de novo bone repair and/or regeneration strategies are constantly undergoing-development alongside advances in orthopedic, oro-dental and cranio-maxillo-facial technologies and improvements in bio−/nano-materials. Indeed, there is a remarkably growing need for new oro-dental functional biomaterials that can help recreate soft and hard tissues and restore function and aesthetics of teeth/ dentition and surrounding tissues. In bone tissue engineering, HydroxyApatite minerals (HAp), the most stable CaP/Calcium Phosphate bioceramic and a widely-used material as a bone graft substitute, have been extensively studied for regenerative medicine and dentistry applications, including clinical use. Yet, limitations and challenges owing principally to its bio-mechanical strength, exist and therefore, research and innovation efforts continue to pursue enhancing its bio-effects, particularly at the nano-scale.Methods: Herein, we report on the physico-chemical properties of a novel nanoHydroxyApatite material obtained from the backbone of Salmon fish (patent-pending); an abundant and promising yet under-explored alternative HAp source. Briefly, our nanoS-HAp obtained via a modified and innovative alkaline hydrolysis–calcination process was characterized by X-ray diffraction, electron microscopy, spectroscopy, and a cell viability assay.Results and Discussion: When compared to control HAp (synthetic, human, bovine or porcine), our nanoS-HAp demonstrated attractive characteristics, a promising biomaterial candidate for use in bone tissue engineering, and beyond.