Biomedical Applications of the Biopolymer Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): Drug Encapsulation and Scaffold Fabrication.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biodegradable and biocompatible biopolymer that has gained popularity in the field of biomedicine. This review provides an overview of recent advances and potential applications of PHBV, with special emphasis on drug encapsulation and scaffold construction. PHBV has shown to be a versatile platform for drug delivery, offering controlled release, enhanced therapeutic efficacy, and reduced side effects. The encapsulation of various drugs, such as anticancer agents, antibiotics, and anti-inflammatory drugs, in PHBV nanoparticles or microspheres has been extensively investigated, demonstrating enhanced drug stability, prolonged release kinetics, and increased bioavailability. Additionally, PHBV has been used as a scaffold material for tissue engineering applications, such as bone, cartilage, and skin regeneration. The incorporation of PHBV into scaffolds has been shown to improve mechanical properties, biocompatibility, and cellular interactions, making them suitable for tissue engineering constructs. This review highlights the potential of PHBV in drug encapsulation and scaffold fabrication, showing its promising role in advancing biomedical applications.

Mesenchymal Stem Cell Therapy in Traumatic Spinal Cord Injury: A Systematic Review.

Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.

Global DNA Methylation in Dental Implant Failure Due to Peri-Implantitis: An Exploratory Clinical Pilot Study.

BACKGROUND: Peri-implantitis (PIT) is highly prevalent in patients with dental implants and is a challenging condition to treat due to the limited outcomes reported for non-surgical and surgical therapies. Therefore, epigenetic therapeutics might be of key importance to treat PIT. However, developing epigenetic therapeutics is based on understanding the relationship between epigenetics and disease. To date, there is still scarce knowledge about the relationship between epigenetic modifications and PIT, which warrants further investigations. AIM: The purpose of this study was to evaluate the level of global DNA methylation associated with implant failure (IF) due to PIT compared to periodontally healthy (PH) patients. MATERIAL AND METHODS: A total of 20 participants were initially enrolled in this pilot, exploratory, single-blinded, cross-sectional clinical human study in two groups: 10 in the PH group and 10 in the IF group. In the participants who have completed the study, gingival tissue and bone samples were harvested from each participant and were used to perform global DNA methylation analysis. The percentage of global DNA methylation (5-mC%) was compared (1) between groups (PH and IF); (2) between the subgroups of gingival tissue and bone separately; (3) in the whole sample, comparing gingival tissue and bone; (4) within groups, comparing gingival tissue and bone. Demographic, periodontal, and peri-implant measurements as well as periodontal staging, were also recorded. All statistical comparisons were made at the 0.05 significance level. RESULTS: Out of the initially enrolled 20 patients, only 19 completed the study and, thus, were included in the final analysis; 10 patients in the PH group and 9 patients in the IF group, contributing to a total of 38 samples. One patient from the IF group was excluded from the study due to systemic disease. The mean implant survival time was 10.8 years (2.17-15.25 years). Intergroup comparison, stratified by group, indicated a similar 5-mC% between the PH and IF groups in both gingival tissue and bone (p = 0.599), only in bone (p = 0.414), and only in gingival tissue (p = 0.744). Intragroup comparison, stratified by the type of sample, indicated a significantly higher 5-mC% in gingival tissue samples compared to bone in both the PH and IF groups (p = 0.001), in the PH group (p = 0.019), and in the IF group (p = 0.009). CONCLUSIONS: Within the limitations of this study, higher global DNA methylation levels were found in gingival tissue samples compared to bone, regardless of the study groups. However, similar global DNA methylation levels were observed overall between the IF and PH groups. Yet, differences in the global DNA methylation levels between gingival tissues and bone, regardless of the study group, could reflect a different epigenetic response between various tissues within the same microenvironment. Further studies are necessary to elucidate the present findings and to evaluate the role of epigenetic modifications in IF due to PIT.

Human Cartilage Engineering in an In Vitro Repair Model Using Collagen Scaffolds and Mesenchymal Stromal Cells.

The purpose of this study was to investigate cartilage repair of in vitro lesion models using human bone marrow mesenchymal stromal cells (hBMSCs) with different collagen (Col) scaffolds. Lesions were made in human cartilage biopsies. Injured samples were pre-treated with interleukin 1ß (IL1ß) for 24 h; also, samples were not pre-treated. hBMSCs were seeded on different types of collagen scaffolds. The resulting constructs were placed into the lesions, and the biopsies were cultured for 2 months in chondrogenic medium. Using the modified ICRSII scale, neotissues from the different scaffolds showed ICRS II overall assessment scores ranging from 50% (fibrocartilage) to 100% (hyaline cartilage), except for the Col I +Col II +HS constructs (fibrocartilage/hyaline cartilage, 73%). Data showed that hBMSCs cultured only on Col I +Col II +HS scaffolds displayed a chondrocyte-like morphology and cartilage-like matrix close to native cartilage. Furthermore, IL1ß pre-treated biopsies decreased capacity for repair by hBMSCs and decreased levels of chondrogenic phenotype of human cartilage lesions.

Ovine Mesenchymal Stromal Cells: Morphologic, Phenotypic and Functional Characterization for Osteochondral Tissue Engineering.

INTRODUCTION: Knowledge of ovine mesenchymal stromal cells (oMSCs) is currently expanding. Tissue engineering combining scaffolding with oMSCs provides promising therapies for the treatment of osteochondral diseases. PURPOSE: The aim was to isolate and characterize oMSCs from bone marrow aspirates (oBMSCs) and to assess their usefulness for osteochondral repair using ß-tricalcium phosphate (bTCP) and type I collagen (Col I) scaffolds. METHODS: Cells isolated from ovine bone marrow were characterized morphologically, phenotypically, and functionally. oBMSCs were cultured with osteogenic medium on bTCP and Col I scaffolds. The resulting constructs were evaluated by histology, immunohistochemistry and electron microscopy studies. Furthermore, oBMSCs were cultured on Col I scaffolds to develop an in vitro cartilage repair model that was assessed using a modified International Cartilage Research Society (ICRS) II scale. RESULTS: oBMSCs presented morphology, surface marker pattern and multipotent capacities similar to those of human BMSCs. oBMSCs seeded on Col I gave rise to osteogenic neotissue. Assessment by the modified ICRS II scale revealed that fibrocartilage/hyaline cartilage was obtained in the in vitro repair model. CONCLUSIONS: The isolated ovine cells were demonstrated to be oBMSCs. oBMSCs cultured on Col I sponges successfully synthesized osteochondral tissue. The data suggest that oBMSCs have potential for use in preclinical models prior to human clinical studies.

* Human Amniotic Mesenchymal Stromal Cells as Favorable Source for Cartilage Repair.

INTRODUCTION: Localized trauma-derived breakdown of the hyaline articular cartilage may progress toward osteoarthritis, a degenerative condition characterized by total loss of articular cartilage and joint function. Tissue engineering technologies encompass several promising approaches with high therapeutic potential for the treatment of these focal defects. However, most of the research in tissue engineering is focused on potential materials and structural cues, while little attention is directed to the most appropriate source of cells endowing these materials. In this study, using human amniotic membrane (HAM) as scaffold, we defined a novel static in vitro model for cartilage repair. In combination with HAM, four different cell types, human chondrocytes, human bone marrow-derived mesenchymal stromal cells (hBMSCs), human amniotic epithelial cells, and human amniotic mesenchymal stromal cells (hAMSCs) were assessed determining their therapeutic potential. MATERIAL AND METHODS: A chondral lesion was drilled in human cartilage biopsies simulating a focal defect. A pellet of different cell types was implanted inside the lesion and covered with HAM. The biopsies were maintained for 8 weeks in culture. Chondrogenic differentiation in the defect was analyzed by histology and immunohistochemistry. RESULTS: HAM scaffold showed good integration and adhesion to the native cartilage in all groups. Although all cell types showed the capacity of filling the focal defect, hBMSCs and hAMSCs demonstrated higher levels of new matrix synthesis. However, only the hAMSCs-containing group presented a significant cytoplasmic content of type II collagen when compared with chondrocytes. More collagen type I was identified in the new synthesized tissue of hBMSCs. In accordance, hBMSCs and hAMSCs showed better International Cartilage Research Society scoring although without statistical significance. CONCLUSION: HAM is a useful material for articular cartilage repair in vitro when used as scaffold. In combination with hAMSCs, HAM showed better potential for cartilage repair with similar reparation capacity than chondrocytes.

Expression of Wnt gene family and frizzled receptors in head and neck squamous cell carcinomas.

Genes of the Wnt and Frizzled class, expressed in HNSCC tissue and cell lines, have an established role in cell morphogenesis and differentiation, and also they have oncogenic properties. We studied Wnt and Fz genes as potential tumor-associated markers in HNSCC by qPCR. Expression levels of Wnt and Fz genes in 22 unique frozen samples from HNSCC were measured. We also assessed possible correlation between the expression levels obtained in cancer samples in relation to clinicopathologic outcome. Wnt-1 was not expressed in the majority of the HNSCC studied, whereas Wnt-5A was the most strongly expressed by the malignant tumors. Wnt-10B expression levels were related with higher grade of undifferentiation. Related to Fz genes, Fz-5 showed more expression levels in no-affectation of regional lymph nodes. Kaplan-Meier survival analyses suggest a reduced time of survival for low and high expression of Wnt-7A and Fz-5 mRNA, respectively. qPCR demonstrated that HNSCC express Wnt and Fz members, and suggested that Wnt and Fz signaling is activated in HNSCC cells.

Tratamiento de lesiones del cartílago articular con terapia celular / Treatment of joint cartilage lesions with cell therapy

Las lesiones del cartílago articular que no afectan a la integridad del hueso subcondral no se reparan espontáneamente. El carácter asintomático de estas lesiones propicia la progresiva degeneración articular y el desarrollo de un proceso artrósico. Para evitar la necesidad de reemplazo protésico, se han desarrollado distintos tratamientos celulares con el objetivo de fomar un tejido de reparación con estructura, composición bioquímica y comportamiento funcional iguales que los del cartílago articular natural. Las técnicas basadas en facilitar el acceso al sistema vascular generan un tejido de reparación fibrocartilaginoso que no reúne las condiciones del cartílago articular. El implante de condrocitos autólogos y la mosaicoplastia autóloga aportan un tejido de reparación de mayor calidad, pero ambas técnicas implican la escisión de cartílago sano, bien para obtener una elevada cantidad de condrocitos, bien para extraer cilindros osteocondrales que se implantan en el defecto. Las células madre mesenquimales constituyen una prometedora herramienta de reparación del cartílago articular en fase de experimentación. Aunque las estrategias actuales de terapia celular producen mejorías clínicas y funcionales, todavía no es posible generar un tejido de reparación resistente a la degeneración y con características de cartílago articular normal (AU)

Articular cartilage lesions which do not affect the integrity of subchondral bone, they are not able to repair it expontaneously. The asymptomatic nature of these lesions induces articular cartilage degeneration and development of an arthrosic process. To avoid the necessity to receive joint replacement surgery, it has been developed different treatments of cellular therapy which are focused to create new tissues whose structure, biochemistry composition and function will be the same than native articular cartilage. Approaches used to access the stream produce a fibrocartilaginose tissue which is not an articular cartilage. Implantation of autologous chondrocytes and autologous mosaicplasties induces a quality better articular cartilage. Furthermore both techniques involve damage in the sane cartilage; because of trying to get a big amount of chondrocytes or because of extraction osteochondral cylinder which will be implanted in the injured joint. The stem cells are a promising toll to repair articular cartilage, however they are in a previous experimentation step yet. Although the present studies using cellular therapy improves clinically and functionally, it is not able to regenerate an articular cartilage which offer resistance the degeneration process (AU)

[Treatment of joint cartilage lesions with cell therapy]. / Tratamiento de lesiones del cartílago articular con terapia celular.

Articular cartilage lesions which do not affect the integrity of subchondral bone, they are not able to repair it expontaneously. The asymptomatic nature of these lesions induces articular cartilage degeneration and development of an arthrosic process. To avoid the necessity to receive joint replacement surgery, it has been developed different treatments of cellular therapy which are focused to create new tissues whose structure, biochemistry composition and function will be the same than native articular cartilage. Approaches used to access the stream produce a fibrocartilaginose tissue which is not an articular cartilage. Implantation of autologous chondrocytes and autologous mosaicplasties induces a quality better articular cartilage. Furthermore both techniques involve damage in the sane cartilage; because of trying to get a big amount of chondrocytes or because of extraction osteochondral cylinder which will be implanted in the injured joint. The stem cells are a promising toll to repair articular cartilage, however they are in a previous experimentation step yet. Although the present studies using cellular therapy improves clinically and functionally, it is not able to regenerate an articular cartilage which offer resistance the degeneration process.