Alleviation of peripheral sensitization by quadriceps insertion of cog polydioxanone filaments in knee osteoarthritis rats.

A recently established therapeutic strategy, involving the insertion of biodegradable cog polydioxanone filaments into the quadriceps muscles using the Muscle Enhancement and Support Therapy (MEST) device, has demonstrated significant efficacy in alleviating knee osteoarthritis (OA) pain. This study investigated changes in peripheral sensitization as the potential mechanism underlying MEST-induced pain relief in monoiodoacetate (MIA) induced OA rats. The results revealed that MEST treatment potently reduces MIA-induced sensitization of L3/L4 dorsal root ganglion (DRG) neurons, the primary nociceptor pathway for the knee joint. This reduction in DRG sensitization, as elucidated by voltage-sensitive dye imaging, is accompanied by a diminished overexpression of TRPA1 and NaV1.7, key nociceptor receptors involved in mechanical pain perception. Importantly, these observed alterations strongly correlate with a decrease in mechanically-evoked pain behaviors, providing compelling neurophysiological evidence that MEST treatment alleviates OA pain by suppressing peripheral sensitization.

In Vitro and in Vivo Biocompatibility and Degradability Evaluation of Modified Polydioxanone Plate.

BACKGROUND: Polydioxanone (PDS) has been widely used in the medical field over the past 30 years. In the 2000s, PDS plate began to be used for rhinoplasty and septoplasty. However, in Asia PDS plates are not widely used due to lack of awareness and high prices. The authors devised a method of producing a modified PDS (m-PDS; Rhinoblock Material & Design Co., Gyeonggi-do, Sothh Korea) at low cost, and compared the biocompatibilities and degradabilities of plates produced with m-PDS and commercial PDS plates (Ethicon, Somerville, NJ) in vivo and in vitro. METHODS: The melting point and decomposition rate of m-PDS were determined by differential scanning calorimetry and thermogravimetric analysis and its tensile strength was also measured. Implants (1 cm × 1 cm × 0.15 mm sized) were inserted subcutaneously into mice and harvested en bloc 2, 5, 10, 15, or 25 weeks later. Tissues were stained with hematoxylin and eosin or Masson's trichrome to evaluate inflammation, extracellular matrix deposition, and vascularization, and plate degradability was also assessed. RESULTS: No significant difference was observed between the thermal analysis and tensile test results of m-PDS and PDS plates. m-PDS started to degrade in vivo from around 10 weeks, and commercial PDS plates from around 15 weeks. After 25 weeks in vivo, both products were completely degraded and not observed in tissue slides. Histologic analysis of excised specimens showed m-PDS and PDS were similar in terms of inflammation, extracellular matrix deposition, and vascularization. CONCLUSION: In vivo and in vitro experiments detected no significant difference between the biocompatibilities and degradabilities of modified and commercial PDS plates. The results of this study suggest that the modified PDS can be used to produce versatile, low cost, absorbable graft materials for rhinoplasty and septoplasty.

A novel patient-specific three-dimensional drug delivery construct for regenerative endodontics.

Evoked bleeding (EB) clinical procedure, comprising a disinfection step followed by periapical tissue laceration to induce the ingrowth of undifferentiated stem cells from the periodontal ligament and alveolar bone, is currently the only regenerative-based therapeutic approach to treating pulp tissue necrosis in undeveloped (immature) permanent teeth approved in the United States. Yet, the disinfection step using antibiotic-based pastes leads to cytotoxic, warranting a biocompatible strategy to promote root canal disinfection with no or minimal side-effects to maximize the regenerative outcomes. The purpose of this investigation was to develop a tubular three-dimensional (3D) triple antibiotic-eluting construct for intracanal drug delivery. Morphological (scanning electron microscopy), chemical (Fourier transform infrared spectroscopy), and mechanical (tensile testing) characteristics of the polydioxanone-based triple antibiotic-eluting fibers were assessed. The antimicrobial properties of the tubular 3D constructs were determined in vitro and in vivo using an infected (Actinomyces naeslundii) dentin tooth slice model and a canine method of periapical disease, respectively. The in vitro data indicated significant antimicrobial activity and the ability to eliminate bacterial biofilm inside dentinal tubules. In vivo histological findings demonstrated that, using the EB procedure, the tubular 3D triple antibiotic-eluting construct allowed the formation of an appropriate environment that led to apex closure and the ingrowth of a thin layer of osteodentin-like tissue into the root canal. Taken together, these findings indicate that our novel drug delivery construct is a promising biocompatible disinfection strategy for immature permanent teeth with necrotic pulps. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1576-1586, 2019.

A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation.

Bioengineered tissue scaffolds in combination with cells hold great promise for tissue regeneration. The aim of this study was to determine how the chemistry and fiber orientation of engineered scaffolds affect the differentiation of mesenchymal stem cells (MSCs). Adipogenic, chondrogenic, and osteogenic differentiation on aligned and randomly orientated electrospun scaffolds of Poly (lactic-co-glycolic) acid (PLGA) and Polydioxanone (PDO) were compared. MSCs were seeded onto scaffolds and cultured for 14 days under adipogenic-, chondrogenic-, or osteogenic-inducing conditions. Cell viability was assessed by alamarBlue metabolic activity assays and gene expression was determined by qRT-PCR. Cell-scaffold interactions were visualized using fluorescence and scanning electron microscopy. Cells grew in response to scaffold fiber orientation and cell viability, cell coverage, and gene expression analysis showed that PDO supports greater multilineage differentiation of MSCs. An aligned PDO scaffold supports highest adipogenic and osteogenic differentiation whereas fiber orientation did not have a consistent effect on chondrogenesis. Electrospun scaffolds, selected on the basis of fiber chemistry and alignment parameters could provide great therapeutic potential for restoration of fat, cartilage, and bone tissue. This study supports the continued investigation of an electrospun PDO scaffold for tissue repair and regeneration and highlights the potential of optimizing fiber orientation for improved utility. © 2016 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2843-2853, 2016.

Synthesis, development, characterization and effectiveness of bovine pure platelet gel-collagen-polydioxanone bioactive graft on tendon healing.

Bovine platelet gel (BPG) is an accessible and cost-effective source of growth factors which may have a value in tendon regenerative medicine. We produced a collagen implant (CI) as a tendon proper, covered it with polydioxanone (PDS) sheath to simulate paratenon and finally embedded the BPG as an active source of growth factor within the bioimplant to test whether BPG would be able to accelerate and enhance tendon regeneration and repair. After in vitro characterization of the bioactive grafts, the grafts were implanted in rabbit large tendon defect model. Untreated tendons and tendons treated with either CI or CI-PDS were served as controls for the CI-PDS-BPG. The animals were investigated clinically, ultrasonographically and haematologically for 120 days. After euthanasia, dry matter content, water uptake and delivery characteristics and also gross morphological, histopathological and scanning electron microscopic features of the healing tendons were assessed. In vitro, the activated platelets in the scaffold, released their growth factors significantly more than the controls. BPG also increased cell viability, and enhanced cellular differentiation, maturation and proliferation inside the CI-PDS compared with the controls. In vivo, the BPG modulated inflammation, increased quality and rate of fibroplasia and produced a remodelled tendon that had significantly higher collagen content and superior collagen fibril and fibre differentiation than controls. Treatment also significantly improved tendon water uptake and delivery characteristics, animals' serum PDGF level, CI-PDS biocompatibility and biodegradability and reduced peritendinous adhesions, muscle fibrosis and atrophy. BPG was effective on tendon healing and CI-PDS-BPG may be a valuable bioscaffold in tendon reconstructive surgery.

An electrospun polydioxanone patch for the localisation of biological therapies during tendon repair.

Rotator cuff tendon pathology is thought to account for 30-70 % of all shoulder pain. For cases that have failed conservative treatment, surgical re-attachment of the tendon to the bone with a non-absorbable suture is a common option. However, the failure rate of these repairs is high, estimated at up to 75 %. Studies have shown that in late disease stages the tendon itself is extremely degenerate, with reduced cell numbers and poor matrix organisation. Thus, it has been suggested that adding biological factors such as platelet rich plasma (PRP) and mesenchymal stem cells could improve healing. However, the articular capsule of the glenohumeral joint and the subacromial bursa are large spaces, and injecting beneficial factors into these sites does not ensure localisation to the area of tendon damage. Thus, the aim of this study was to develop a biocompatible patch for improving the healing rates of rotator cuff repairs. The patch will create a confinement around the repair area and will be used to guide injections to the vicinity of the surgical repair. Here, we characterised and tested a preliminary prototype of the patch utilising in vitro tools and primary tendon-derived cells, showing exceptional biocompatibility despite rapid degradation, improved cell attachment and that cells could migrate across the patch towards a chemo-attractant. Finally, we showed the feasibility of detecting the patch using ultrasound and injecting liquid into the confinement ex vivo. There is a potential for using this scaffold in the surgical repair of interfaces such as the tendon insertion in the rotator cuff, in conjunction with beneficial factors.

Tissue restoration after implantation of polyglycolide, polydioxanone, polylevolactide, and metallic pins in cortical bone: an experimental study in rabbits.

We performed qualitative and histoquantitative investigations of tissue restoration after implanting polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins in the intramedullary canal of rabbit femurs. The effect of bioabsorbable devices on healing of a cortical bone defect was also assessed. The cortical bone defect was created in the right femur of 80 rabbits. Bioabsorbable and metallic pins in 60 and two metallic pins alone were implanted in 20 intramedullary canals; 80 left femurs served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. At all time points, collagenous connective tissue, including bone trabeculae, surrounded the implant at the tissue-implant interface, replacing hematopoiesis and fat of the intramedullary canal. The groups did not differ in the area and trabecular bone area fraction of the resulting callus. Residual fragments of PGA and PDS were observed at 24 weeks, and complete degradation occurred within 52 weeks. PGA, PDS, PLLA, and metallic implants induced a bony and fibrous walling-off response in the intramedullary cavity. No inflammation was observed. Complete tissue restoration did not occur within the follow-up, even after complete degradation of PGA and PDS, which had shorter degradation times than PLLA. The cortical bone healing effect was not different between bioabsorbable pins and metallic wires. Thus, these polymers had no specific osteostimulatory or osteoinhibitory properties compared to stainless steel. Within the follow-up period, there were no significant differences in biocompatibility between the implants and no adverse inflammatory foreign-body reactions.

Modulation of murine innate and acquired immune responses following in vitro exposure to electrospun blends of collagen and polydioxanone.

In light of cell sourcing issues and the lack of a bioreactor comparable to the body, many in the field of tissue engineering have focused their efforts on designing biomaterials capable of in situ regeneration. The theory is that, by using the body as both the bioreactor and the source for cell infiltration, scaffolds composed of bioresorbable materials can be remodeled into native tissue. Thus, research into the effects of such materials on the host immune response is increasingly important. This study applies an immunotoxicological approach to evaluate the effects of electrospun blends of polydioxanone (PDO) and collagen type I on murine innate and acquired immune responses. Results indicated that these materials had few effects on innate immune responses, yet they produced significant immunomodulatory effects in multiple endpoints evaluating both branches of acquired immunity (i.e., cell-mediated and humoral immunity). Specifically, collagen content appeared to be responsible for suppression of cell-mediated immunity, while blends of PDO and collagen appeared to be more suppressive of antibody-forming cell responses than either PDO or collagen alone. These results demonstrate the importance of completing evaluations into the immunotoxicological effects of biomaterials, and they suggest that such testing should become a primary focus when evaluating a material's potential foruse in tissue engineering applications.

A biomimetic tubular scaffold with spatially designed nanofibers of protein/PDS bio-blends.

Electrospun tubular conduit (4 mm inner diameter) based on blends of polydioxanone (PDS II(R)) and proteins such as gelatin and elastin having a spatially designed trilayer structure was prepared for arterial scaffolds. SEM analysis of scaffolds showed random nanofibrous morphology and well-interconnected pore network. Due to protein blending, the fiber diameter was reduced from 800-950 nm range to 300-500 nm range. Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) results confirmed the blended composition and crystallinity of fibers. Pure PDS scaffold under hydrated state exhibited a tensile strength of 5.61 +/- 0.42 MPa and a modulus of 17.11 +/- 1.13 MPa with a failure strain of 216.7 +/- 13%. The blending of PDS with elastin and gelatin has decreased the tensile properties. A trilayer tubular scaffold was fabricated by sequential electrospinning of blends of elastin/gelatin, PDS/elastin/gelatin, and PDS/gelatin (EG/PEG/PG) to mimic the complex matrix structure of native arteries. Under hydrated state, the trilayer conduit exhibited tensile properties (tensile strength of 1.77 +/- 0.2 MPa and elastic modulus of 5.74 +/- 3 MPa with a failure strain of 75.08 +/- 10%) comparable to those of native arteries. In vitro degradation studies for up to 30 days showed about 40% mass loss and increase in crystallinity due to the removal of proteins and "cleavage-induced crystallization" of PDS.

Implantation sites and fiber diameters affect the rate of degradation in absorbable polydioxanone fibers.

PURPOSE: The purpose of this study is to test the question of whether implantation sites and fiber diameters affect the rate of degradation in absorbable polydioxanone fibers. TYPE OF STUDY: Randomized trial. METHODS: Forty-eight mature rabbits were used. In the first study, using 24 rabbits, a 0.3-mm diameter polydioxanone fiber was implanted into the subcutaneous, intra-articular, and intramedullary sites. Six rabbits each were killed at 1, 2, 3, and 6 weeks after surgery. In the second study, the remaining 24 rabbits were divided into 2 groups of 12 animals each. In group I, a 0.3-mm diameter fiber was implanted into the intramedullary and subcutaneous sites. In group II, a 0.6-mm diameter fiber was implanted in the same manner. In each group, 6 rabbits were killed at 3 and 6 weeks. In each study, all fiber specimens underwent tensile testing to determine the material properties. We defined the percentage of the maximum load of each fiber specimen compared with the normal control value as the I/N ratio. RESULTS: In the first study, the maximum load and the stiffness of the fibers implanted into the intramedullary site were significantly lower than those of the fibers implanted into the other 2 sites at each period (P <.0001). In the second study, the I/N ratio of group I was significantly less than that of group II at each implanted site (P <.0001). CONCLUSIONS: Polydioxanone fiber implanted into the intramedullary site deteriorates more rapidly than that implanted into the subcutaneous and the intra-articular sites. Thin fibers deteriorate more rapidly than thick fibers. Therefore, the degradation of absorbable synthetic fibers intended for use in ligament reconstruction should be evaluated not only in the subcutaneous site but also in the intramedullary site using various diameter fibers.

Determination of the 3-D morphology of degradable biopolymer implants undergoing in vivo resorption.

A technique is presented that allows the visualization of the degradation process of biopolymers. Serial thick-section specimens containing cross-sections of polydioxanone implants (PDAs) were realigned for 3-D reconstruction using a double-embedding technique. The outlines of the cross-sectioned implants were traced using an automatic image analysis system and converted into x, y, and z coordinates. The reconstruction of the implant body was achieved by the stepwise analysis of vertical relationships between two adjacent section levels. The surface was approximated by triangulation and calculated from the surface triangles. Visualization was achieved by introducing the data into commercially available software using z-buffering and Gouraud shading. The geometric precision of the reembedding technique was found to be 0.8-1.5% of the screen width; recovering experiments showed a good approximation to the actual physical volume of unresorbed implants (+/- 2.6%). The error of volume determination due to the limited resolution in the z direction was calculated to be acceptable (< 5.0%) in isotropic objects where the ratio between the radius of the surface curvature and the distance between the sections is > 4. Results indicate that large devices of PDAs are degraded in vivo in a fashion similar to that previously described for in vitro degradation of PLA molded screws by a surface/center differentiation with formation of hollow residuals after 17 weeks and complete degradation with phagocytosis of microparticles after 26 weeks.

Biodegradation of polydioxanone in bone tissue: effect on the epiphyseal plate in immature rabbits.

Implants of polydioxanone (PDS), 1.3 mm in diameter, were operatively fixed in the juxta-epiphyseal area of the right proximal tibial metaphysis in six rabbits and were driven into a drill hole of equal bore through the right proximal tibial epiphyseal plate in ten rabbits. The PDS implants had biodegraded almost completely in cortical bone at 16 weeks without any significant sign of inflammation or foreign body reaction. The PDS implants did not cause any growth disturbance. Histologic studies, however, showed that seven of 10 rabbits demonstrated significant osseous bridge formation across the epiphyseal plate.