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Polydioxanone

Polydioxanone is a synthetic, semi-crystalline derived from the of p-dioxanone monomer, widely utilized in biomedical applications due to its and controlled hydrolytic . With a consisting of repeating -[O-CH₂-CH₂-O-CO-CH₂]- units and a number of 31621-87-1, it exhibits a of approximately 110–115°C and a temperature of -10°C to 0°C, rendering it flexible and suitable for and molding processes. Introduced in the early 1980s, polydioxanone has become a cornerstone material for absorbable medical devices, including monofilament sutures like PDS™ II, which maintain tensile strength for 4–6 weeks before complete resorption in 6–9 months. The polymer's degradation occurs via bulk hydrolytic erosion, breaking down into non-toxic metabolites such as , , and , which are primarily excreted in with minimal inflammatory response or reaction. Mechanically, it offers a of around 1.5 GPa and initial high tensile strength, though it is more flexible and weaker compared to other polyesters like polyglycolic acid or , with crystallinity levels of 55–60% that influence its processability. Its nonantigenic and nonpyrogenic nature ensures excellent , making it ideal for short- to medium-term implants in fields such as , orthopedics, and otolaryngology. Beyond sutures, polydioxanone finds applications in resorbable stents, orthopedic pins and screws (e.g., Orthosorb®), clips, staples, meshes, and plates, as well as emerging uses in scaffolds and systems. Since receiving FDA approval for surgical uses in , over 48 polydioxanone-based devices have been cleared, highlighting its safety profile with low rates of complications like or in clinical settings. Manufacturing challenges, such as sensitivity to light and , are addressed through specialized techniques like low-temperature , enabling its adaptation for advanced formats including filaments.

Chemical Structure and Synthesis

Monomer Structure

p-Dioxanone, systematically named 1,4-dioxan-2-one, serves as the key monomer for synthesizing polydioxanone through . Its molecular formula is C₄H₆O₃, corresponding to a six-membered heterocyclic classified as a cyclic diester or . p-Dioxanone is typically synthesized by the acid-catalyzed reaction of with or through esterification and cyclization of derivatives, followed by for purification. The comprises two oxygen atoms positioned at carbons 1 and 4, with a attached to carbon 2, forming an linkage adjacent to an bridge (–O–CH₂–CH₂–O–CH₂–C(=O)– in cyclic form). This arrangement results in an achiral molecule with no stereocenters, adopting a chair-like conformation typical of six-membered rings. The moderate ring strain in p-dioxanone, arising from the cyclic ester configuration, facilitates its polymerization reactivity despite being lower than that observed in smaller-ring lactones like β-propiolactone, where strain is inversely proportional to ring size. This strain energy provides a thermodynamic driving force for ring opening, enabling efficient conversion to linear polymer chains under appropriate catalytic conditions. The monomer's dual ether and ester functionalities play a pivotal role in defining the resulting polymer's characteristics; the ether group imparts flexibility and hydrophilicity to the backbone, while the ester linkage ensures susceptibility to hydrolytic degradation. This combination yields a poly(ester-ether) material with balanced mechanical compliance and bioresorbability, distinct from purely polyester homologs.

Polymerization Methods

Polydioxanone (PPDO) is primarily synthesized via (ROP) of p-dioxanone (PDO) , a process that transforms the cyclic into a linear chain. This method dominates due to its ability to produce high-molecular-weight polymers with controlled structures suitable for biomedical applications. The ROP of PDO typically proceeds through a coordination-insertion , wherein the catalyst coordinates to the 's carbonyl oxygen, promoting nucleophilic attack by the active chain end and selective acyl-oxygen bond cleavage. An active chain-end can also occur, particularly with certain initiators, where the propagating species directly attacks the without strong catalyst coordination. These mechanisms allow for living-like characteristics, minimizing side reactions like under optimized conditions. Key catalysts include stannous octoate [Sn(Oct)2] and aluminum isopropoxide [Al(OPr)3], often used with alcohol initiators such as lauryl alcohol to control chain length. These catalysts influence molecular weight by modulating propagation rates and termination events; for instance, lower catalyst concentrations yield higher molecular weights due to reduced chain transfer. Stannous octoate, in particular, is widely adopted for its efficiency in bulk polymerizations and FDA approval for medical-grade PPDO. Reaction parameters critically affect yield and polymer properties: temperatures of 100–120°C promote rapid monomer conversion while avoiding thermal degradation, with bulk or solution (e.g., ) media preferred to minimize impurities. times typically range from 6 to 24 hours, balancing conversion (often >90%) and molecular weight control. Under these conditions, PPDO achieves number-average molecular weights of 50,000–200,000 g/, with polydispersity indices (PDI) of 1.5–2.5 reflecting moderate chain length distributions. The overall ROP reaction is depicted as: n \ce{C4H6O3} \rightarrow \ce{[-O-(CH2)2-O-CO-CH2-]_{n}}

Copolymers and Modifications

Polydioxanone (PDO) is frequently copolymerized with glycolide to form poly(dioxanone-co-glycolide) (PDG), which is synthesized through (ROP) of the respective monomers, often in a sequential manner to control microstructure and composition. In this process, p-dioxanone is first polymerized, followed by the addition of glycolide, using catalysts like stannous octoate, resulting in copolymers with tailored lengths that enhance flexibility and rates compared to the homopolymer. These copolymers exhibit faster hydrolytic degradation than pure PDO due to the incorporation of more hydrophilic glycolide units, with degradation mechanisms involving surface erosion and reduced molecular weight over time in aqueous environments. Similarly, copolymers of PDO with , such as poly(d,l--co-p-dioxanone), are prepared via bulk ROP in one-step or two-step processes using stannous octoate and an initiator like n-dodecanol, allowing for random or segmented architectures depending on the sequence of . The two-step method, involving initial polymerization of p-dioxanone at lower temperatures followed by , yields semi-crystalline structures with longer sequence lengths when PDO content exceeds 14.5 %, leading to improved pliability and reduced relative to polylactide homopolymers. Higher PDO incorporation in these copolymers accelerates degradation rates, with in vitro showing more pronounced molecular weight loss than in lactide-rich variants, while maintaining single temperatures that vary linearly with composition. Surface modifications of PDO, such as plasma treatment, introduce functional groups to alter hydrophobicity and enhance tissue interactions, as demonstrated by low-pressure plasma exposure of PDO sutures, which improves tensile strength retention during without affecting bending stiffness. Grafting or blending with hydrophilic agents like (PVA) at 5 wt% via melt-molding further hydrophilizes PDO scaffolds, promoting better and by increasing surface wettability and facilitating tissue infiltration in porous structures. Blends of PDO with (PCL) or () are used to optimize mechanical performance, with immiscible PDO/PCL mixtures showing tunable tensile strength and elongation through phase morphology control during processing. For instance, PDO/ blends exhibit enhanced thermal and morphological uniformity, resulting in higher impact resistance and suited for load-bearing applications like scaffolds. These modifications generally accelerate degradation in glycolide-containing copolymers while improving mechanical toughness in blends, enabling targeted uses in resorbable implants.

Physical and Chemical Properties

Mechanical Properties

Polydioxanone (PDO) exhibits initial tensile strength in the range of 40-50 , which provides sufficient load-bearing capacity for applications such as surgical sutures, though this strength decreases over time due to its inherent material characteristics. The elongation at break for PDO monofilaments typically ranges from 20-30% under standard testing conditions, offering a balance of and that allows for deformation without immediate . The of PDO is approximately 1-2 GPa, reflecting its semi-crystalline structure, with higher values associated with increased crystallinity levels achieved through processing techniques like annealing. Crystallinity enhances , as the ordered regions contribute to greater resistance to deformation, while amorphous domains provide flexibility. In monofilament form, PDO demonstrates good fatigue resistance, particularly to bending and abrasion, outperforming some braided sutures in cyclic loading scenarios relevant to dynamic environments. Knot strength in these monofilaments is reliable, with secure knotting achieved through multiple throws, maintaining a significant portion of the straight tensile strength. Mechanical performance of PDO is strongly influenced by molecular weight and processing methods. Higher molecular weights, typically above 100,000 g/mol, correlate with improved tensile strength and due to longer chain entanglements that enhance load transfer. factors such as injection molding and post-annealing (e.g., at 90°C for 2 hours) can optimize crystallinity and thus elevate modulus and strength, with annealing increasing tensile values by up to 79% compared to unprocessed material. In comparison to non-absorbable sutures like , PDO offers lower (approximately half that of polypropylene monofilaments) but superior elongation and handling properties, making it suitable for temporary support in biodegradable applications.

Thermal and Chemical Stability

Polydioxanone exhibits a temperature () of approximately -10 °C, which contributes to its flexibility and toughness at physiological temperatures, and a (Tm) around 110 °C, enabling methods such as injection molding without excessive degradation. These thermal transitions are determined through (), highlighting the polymer's semicrystalline nature with a window limited by its relatively low Tm. Thermal gravimetric analysis () reveals that polydioxanone maintains stability up to about 190 °C, beyond which decomposition initiates primarily through to the p-dioxanone , followed by , with no significant residue left in an inert atmosphere. At higher heating rates, the decomposition onset can shift to around 260 °C, underscoring the material's suitability for melt processing below this threshold to avoid chain shortening and mass loss. In aqueous environments, polydioxanone demonstrates hydrolytic stability that is highly -dependent, with degradation rates remaining low and linear at neutral (3.78–7.4), leading to gradual reduction over 8–10 weeks, but accelerating dramatically at acidic ≤1.67, where drops to 15% of initial values within one week due to catalyzed bond . This sensitivity arises from the vulnerability of its linkages to in acidic media, promoting random or end-chain scission without altering the overall . For sterilization, gamma irradiation at standard doses (e.g., 25–35 kGy) induces chain scission in polydioxanone, significantly reducing molecular weight (both Mw and ) and inherent while broadening the molecular weight distribution, though it minimally affects thermal properties like . The linkages in polydioxanone are chemically reactive toward acids, undergoing accelerated in acidic conditions; while base-catalyzed also occurs, quantitative effects in alkaline media are less studied compared to acidic .

Solubility and Morphology

Polydioxanone (PDO) is soluble in select organic solvents, including and hexafluoroisopropanol (HFIP), which facilitates its processing into films, fibers, and other forms through solution-based techniques such as casting or . Conversely, PDO remains insoluble in and alcohols, a property stemming from its hydrophobic backbone, which limits its direct use in aqueous environments but enhances its stability in biomedical applications prior to implantation. The exhibits semi-crystallinity, typically ranging from 30% to 60%, depending on conditions and molecular weight. This crystallinity can be precisely controlled through post- methods like annealing, which promotes reorganization of polymer chains into more ordered structures, or , which aligns molecules to enhance and crystalline fraction in forms. Scanning electron microscopy (SEM) and (TEM) analyses of PDO monofilaments reveal a fibrillar with smooth, cylindrical cross-sections and longitudinally aligned crystalline lamellae, particularly in drawn sutures where surface uniformity supports low drag. Within PDO's microstructure, amorphous domains enable faster of small molecules, such as solvents or , compared to the densely packed crystalline regions, which act as barriers and thereby influence overall mass transport and efficiency. During melt , PDO displays non-Newtonian shear-thinning , characterized by a decrease in under high rates, while its zero- rises with increasing molecular weight, allowing for controlled into monofilaments or films at temperatures around 100–120°C.

Biodegradation and Biological Interactions

Degradation Mechanisms

Polydioxanone (PDO), a , primarily degrades through hydrolytic cleavage of its bonds in aqueous environments, where molecules attack the carbonyl groups, resulting in random chain scission and the formation of hydroxyl and end groups. This process can be represented by the simplified equation: -[O-R-CO]- + H_2O \rightarrow HO-R-OH + HOOC- The carboxylic acids produced during act as autocatalysts, accelerating further by lowering the local and enhancing bond reactivity. studies at physiological conditions (37°C, 7.4) reveal a heterogeneous pattern, with initial preferential attack on amorphous regions before progressing to crystalline domains, leading to a two-stage process: an initial dormant phase of chain scission upon , followed by an active phase with measurable morphological and property changes after approximately 15 days. PDO exhibits bulk erosion rather than surface erosion, as water penetrates the entire polymer matrix rapidly compared to the rate of bond hydrolysis, resulting in uniform molecular weight reduction throughout the material without significant surface layer loss until advanced stages. Molecular weight loss profiles show a gradual decline in viscosity-average molecular weight, with only minor mass loss (around 3%) after 10 weeks, but substantial reductions (e.g., from 130 kg/mol to below 8 kg/mol) correlating with increased crystallinity and loss of mechanical integrity. The in vitro half-life under these conditions is typically 3-6 months, reflecting the slow kinetics dominated by hydrolysis. Enzymatic degradation of PDO involves lipase enzymes, such as or , which catalyze the of linkages through specific chain-end or intra-chain scission, producing low-molecular-weight oligomers more efficiently than non-enzymatic . This pathway proceeds optimally at 37°C in solution, with immobilized lipases demonstrating higher thermal stability and degradation rates, though it remains secondary to hydrolytic mechanisms in most contexts.

In Vivo Behavior

In vivo, polydioxanone (PDO) exhibits a controlled degradation profile primarily through , with the typically retaining sufficient mechanical integrity for initial support while gradually losing strength over time. Studies indicate that PDO monofilaments lose approximately 50% of their initial tensile strength within 4 to 6 weeks post-implantation, allowing for during this period, followed by complete absorption within 6 to 12 months depending on the implant form and environmental conditions. This timeline contrasts with faster-degrading polymers like polyglycolic acid, providing prolonged support in applications such as sutures. The degradation elicits a minimal response, characterized by transient, low-grade that resolves without significant , attributed to the biocompatible nature of PDO and its non-toxic byproducts. Several biological factors modulate the degradation rate of PDO, integrating environmental influences within the body. Implantation site plays a key role, with subcutaneous locations often showing slower compared to more vascularized abdominal or peritoneal sites due to differences in local blood flow, oxygen levels, and cellular infiltration. Local variations, such as those in acidic inflammatory environments, can accelerate hydrolytic cleavage of bonds, while neutral physiological (around 7.4) supports a more predictable rate. Enzymatic activity, particularly from lipases present in tissues, further enhances by catalyzing surface , though this effect is more pronounced in lipid-rich areas. These variables ensure that aligns with tissue remodeling needs, minimizing complications like premature loss of integrity. The byproducts of PDO degradation, including and other low-molecular-weight carboxylic acids, are readily metabolized through the into carbon dioxide and water or excreted primarily via renal pathways. In vivo studies report that up to 93% of these products are eliminated in , with hepatic metabolism handling the remainder, preventing accumulation and contributing to the material's favorable safety profile. Animal model studies, particularly in rats using subcutaneous implantation, have provided key insights into PDO's in vivo performance. In one such model, 3D-printed PDO devices implanted subcutaneously in rats demonstrated complete resorption between 4 and 7 months, accompanied by only transient inflammatory infiltration that peaked at 2-4 weeks and subsided thereafter, with histological analysis showing minimal . Similar rat subcutaneous experiments with PDO-based antibiotic-eluting matrices confirmed , revealing no adverse reactions and rates aligning with the 50% strength loss at 4-6 weeks, underscoring PDO's suitability for applications.

Biocompatibility and Toxicity

Polydioxanone (PDO) is evaluated for biocompatibility under the ISO 10993 standards for biological evaluation of medical devices, which encompass tests for cytotoxicity, sensitization, irritation, genotoxicity, and systemic toxicity. Compliance with these standards has been demonstrated for PDO-based medical devices, such as surgical scaffolds and threads, showing non-cytotoxic, non-irritating, non-sensitizing, and non-mutagenic properties in both in vitro and in vivo assessments. For instance, PDO surgical scaffolds exhibited no evidence of genotoxicity or sensitization in guinea pig maximization tests and Ames assays, confirming their safety for implantation. Additionally, ISO 10993-5 cytotoxicity guidelines classify materials with cell viability above 70% as non-cytotoxic, a threshold consistently met by PDO formulations. Cytotoxicity studies using MTT assays on fibroblasts further underscore PDO's low toxicity profile. In evaluations with fibroblasts and L929 fibroblasts, extracts from PDO threads and meshes yielded cell viabilities ranging from 100% to 155% after 24 hours of exposure, indicating robust cellular metabolic activity without adverse effects. Similarly, MTT tests on human multipotent stromal cells exposed to PDO yarns for up to 5 days showed optical densities comparable to untreated controls, with zero observed. These results highlight PDO's compatibility with proliferation and , essential for applications. The inflammatory response to PDO is characteristically mild and transient, typically resolving within weeks post-implantation. In vivo studies report low rates of inflammation and , with less than 5% incidence for PDO meshes and plates, involving minimal infiltration that shifts to an M2 anti-inflammatory by day 10. Compared to (PLA), PDO induces significantly less inflammation, as PLA's degradation to can cause localized drops and persistent irritation, whereas PDO maintains better integration. Allergenicity assessments, including skin tests under ISO 10993-10, have shown no allergic potential for PDO, with negative responses in animal models. Degradation byproducts of PDO, primarily , , and , exhibit negligible effects on cellular and overall toxicity. These metabolites are either excreted via urine (over 93% elimination) or processed through the to and , without eliciting cytotoxic responses in cultures. In vitro exposure of VERO and MDCK to PDO hydrolyzates for up to 48 hours via MTT assays confirmed no disruption to cell adherence, proliferation, or metabolic function, supporting PDO's suitability as a with minimal byproduct-related risks.

Production and Commercialization

Manufacturing Techniques

Polydioxanone (PDO) production begins with of , typically using catalysts such as stannous octoate, to form the base resin, which is then processed into final forms via techniques. For monofilament production, is the primary method, involving of molten PDO through a followed by drawing to orient the polymer chains and enhance strength. The polymer is extruded at temperatures between 120°C and 140°C to ensure flowability above its of approximately 110°C, with the filament cooled in a to solidify it. Drawing occurs in multiple stages using godets, with draw ratios typically ranging from 2.5 to 6.5, reducing filament diameter from around 1 mm to 350–780 μm depending on the ratio, thereby improving tensile properties. Injection molding is employed to fabricate devices such as implants and surgical tools from PDO pellets. The process heats the to a melt of 110–150°C, followed by injection into a under pressures of 500–1300 , with hold times of at least 5 seconds to allow . are maintained at 20–65°C to control cooling rates and final crystallinity, influencing and ; lower (e.g., 25°C) yield more ductile parts with Young's modulus around 545 , while higher ones (e.g., 65°C) produce stiffer structures up to 786 . Retained pressure of 150–650 ensures part integrity without defects like voids. Sterilization of PDO materials is critical for biomedical applications and commonly uses (EtO) or to achieve sterility assurance levels without excessive degradation. EtO gas penetration at low temperatures preserves structural integrity, surface texture, and mechanical properties better than methods, with minimal changes to melting temperature or crystallinity in variants. (typically 25–40 kGy) effectively kills microorganisms but can reduce by chain scission, increasing and potentially accelerating degradation, though it minimally affects wettability and overall when doses are controlled. Both methods maintain cell viability above 70% post-treatment, confirming non-toxicity. Quality control in PDO manufacturing relies on techniques like (GPC) to monitor molecular weight distribution, ensuring number-average values around 100,000–110,000 g/mol and weight-average around 220,000–250,000 g/mol for consistent degradation profiles. (DSC) assesses crystallinity (typically 40–45%) by analyzing melting and peaks, with Avrami exponents of 2.8–3.8 indicating spherulitic growth, which correlates with mechanical performance and process . Scale-up from laboratory to industrial production of PDO presents challenges in catalyst removal and impurity control to meet biocompatibility standards. Residual catalysts like stannous octoate or zinc compounds must be thoroughly extracted via precipitation or filtration to below detectable limits, as traces can accelerate unintended degradation or elicit toxicity in vivo. Impurity control involves purifying the p-dioxanone monomer to minimize water or hydroxyl contaminants that limit molecular weight, with vacuum devolatilization during polymerization aiding scale-up, though uniform heat transfer in larger reactors remains a hurdle for consistent yields above 90%.

Commercial Products and Trade Names

Polydioxanone is primarily commercialized as absorbable monofilament sutures under the trade name PDS® II by , a of , marking the first such synthetic product introduced in 1981 for soft tissue approximation, including in pediatric cardiovascular and ophthalmic procedures. These sutures are available in USP sizes from 7-0 to 2, with common configurations in sizes 0 to 4-0, lengths of 18 to 45 inches, and violet or undyed options; they are widely available through global distributors. Beyond sutures, polydioxanone is used in orthopedic applications as OrthoSorb® absorbable pins by DePuy Mitek (Johnson & Johnson), introduced for temporary bone fixation in procedures like fracture repair and cartilage stabilization, available in diameters of 1.3 mm to 2.0 mm and lengths up to 40 mm. Other manufacturers, such as DemeTECH and Medico, produce generic polydioxanone sutures under trade names like DemeDIOX® and Polydioxanone Suture, contributing to market diversity. In , polydioxanone is commercialized as PDO threads for non-surgical facial ing and skin rejuvenation procedures. These threads, often barbed or smooth, are used to stimulate and provide mechanical , with major brands including NovaThreads® by Aesthetic Management Systems and generic variants from suppliers like Cog Thread. The global PDO threads market was valued at approximately USD 109 million in and is projected to reach USD 187 million by 2032. In the cardiovascular field, polydioxanone-based bioresorbable stents remain largely investigational, with prototypes like 3D-printed variants evaluated for endovascular use but not yet approved for widespread commercial distribution. PDS® II sutures maintain a prominent position in the absorbable monofilament segment, supported by & Johnson's global patents and manufacturing, alongside competitors like in the broader absorbable suture market.

Regulatory Aspects

Polydioxanone (PDO)-based medical devices, such as sutures and implants, are regulated as Class II devices by the U.S. Food and Drug Administration (FDA) under 21 CFR 878.4840 when used for soft tissue approximation, requiring 510(k) premarket notification and adherence to special controls like performance testing and labeling guidelines. Certain higher-risk PDO implants, including those for structural support in load-bearing applications, may be classified as Class III, necessitating premarket approval (PMA) to demonstrate safety and effectiveness through clinical data. In the , PDO devices obtain under the Medical Device Regulation (MDR) 2017/745, typically as Class IIa for absorbable sutures or Class IIb/III for implantable devices, involving conformity assessment by a to ensure compliance with essential requirements for design, manufacturing, and risk management. Manufacturers must also implement a certified to :2016, which specifies requirements for the design, production, and post-production processes of medical devices to maintain consistent safety and efficacy. Biocompatibility of PDO materials is evaluated under (USP) Class VI standards, which test for systemic toxicity, intracutaneous reactivity, and implantation effects; PDO homopolymers have been demonstrated to pass these criteria, confirming suitability for prolonged contact with body tissues. Post-market surveillance for PDO devices in the U.S. includes mandatory adverse event reporting to the FDA's Manufacturer and User Facility Device Experience (MAUDE) database; analysis of FDA records from 2009 to 2019 identified 1,294 reports of adverse reactions or malfunctions associated with 48 approved PDO implants, predominantly involving sutures, with low incidence rates of infections (under 5%) and foreign body responses. Global regulatory harmonization for PDO and similar absorbable polymers is advanced through the International Medical Device Regulators Forum (IMDRF), which provides guidelines on essential principles of safety and performance, risk-based classification, and post-market surveillance to align requirements across member countries and facilitate .

Applications

Surgical and Biomedical Uses

Polydioxanone (PDS) is widely utilized as an absorbable monofilament suture material for approximation in surgical procedures, particularly in gastrointestinal and urogenital applications. Its smooth surface minimizes tissue drag and reduces the risk of bacterial adherence compared to braided sutures, facilitating easier passage through tissues. In gastrointestinal , PDS sutures are employed for closures in colonic and intestinal anastomoses, where their prolonged tensile strength supports without the need for suture removal. Similarly, in urogenital procedures, such as and urethral repairs, PDS demonstrates effective handling and low reactivity in urinary environments. In , polydioxanone extends beyond sutures to include bioabsorbable implants like screws, plates, and pins for bone fixation, especially in small cancellous fractures. These implants provide initial mechanical stability while degrading over time, eliminating the need for secondary removal surgeries and reducing long-term complications associated with metallic hardware. Clinical studies have confirmed their safety and performance in pediatric and adult orthopedic cases, with resorption occurring without significant adverse tissue reactions. For cardiovascular applications, polydioxanone is incorporated into vascular grafts and occluders for septal defect closures. Hybrid vascular grafts combining PDS with other polymers offer high mechanical strength and gradual degradation, supporting vessel remodeling. In septal defect repairs, fully biodegradable PDS occluders have shown efficacy in closing ventricular septal defects, with complete resorption allowing for natural and minimal residual shunts. Clinical outcomes with polydioxanone sutures highlight improved safety profiles, including reduced rates compared to due to lower reactivity and inflammatory response. PDS retains approximately 70-90% of its initial tensile strength at two weeks post-implantation, providing reliable support during the critical early healing phase. In , PDS's absorbability accommodates patient growth, as demonstrated in cardiovascular anomaly repairs where suture lines expand without constriction, minimizing reoperation needs.

Tissue Engineering and Drug Delivery

Polydioxanone (PDO) has emerged as a promising in due to its , tunable degradation, and ability to form nanofibrous structures that mimic the . In , PDO scaffolds fabricated via provide porous architectures that support cell infiltration and tissue ingrowth, facilitating the repair of complex tissues. These scaffolds degrade hydrolytically over 6-12 months, allowing gradual transfer of mechanical load to regenerating tissue while minimizing inflammatory responses. In and regeneration, PDO scaffolds offer mechanical support and bioactivity essential for osteogenesis and chondrogenesis. For instance, nanofibrous PDO mats with fiber diameters of 0.18-1.4 μm have been produced via . Similarly, intra-articular injections of PDO microspheres in models demonstrated improved regeneration, with histological scores indicating reduced degeneration and increased content compared to controls after 12 weeks. These porous structures, often combined with factors, enable controlled cellular colonization and deposition. For , PDO-based implants enable sustained release of therapeutic agents, such as antibiotics and growth factors, through matrix erosion and diffusion mechanisms. Reservoir-type PDO capsules loaded with exhibit zero-order release kinetics over approximately 4 weeks , which is advantageous for preventing burst effects in postoperative control. Aligned PDO nanofibers in dressings and guides further enhance this capability; electrospun PDO-fucoidan blends support fibroblast attachment via their high surface-to-volume ratio, promoting and essential for epithelialization in . In regeneration, aligned PDO microfibers within conduits promote neuronal alignment and oriented growth, outperforming unaligned fibers. Copolymerization of PDO with monomers like ε-caprolactone or trimethylene carbonate allows fine-tuning of degradation rates and release profiles, extending drug elution from 1 to 4 weeks for applications in localized therapy. For example, PDO-co-polycaprolactone copolymers in nanofibrous implants achieve biphasic release of growth factors, with an initial burst followed by steady diffusion, supporting sustained in tissue defects as evidenced by in vivo vascularization in rat models. In vitro assays on PDO meshes confirm robust and , with cell densities increasing 3-5 fold over 7 days, underscoring their utility in regenerative scaffolds. These enhancements position PDO copolymers as versatile platforms for personalized drug-eluting systems in .

Emerging Non-Medical Uses

In , PDO is incorporated into multi-layered biodegradable films designed for wrapping and semi-solid containment, offering barrier properties against oxygen and while ensuring compostability. These films, often blended with polymers like or , exhibit tensile strengths suitable for short-term use and degrade within 4-24 months in composting conditions, aligning with industrial standards for waste reduction. The material's hydrophobicity in direct-contact layers extends for perishable goods, positioning PDO as a viable alternative to conventional plastics in solutions.

History and Research Developments

Discovery and Early Development

Polydioxanone (PDO), a synthetic biodegradable polymer, was developed in the 1970s by researchers at Ethicon, a subsidiary of Johnson & Johnson, as part of efforts to create improved absorbable monofilament sutures for surgical applications. The polymer's synthesis via ring-opening polymerization (ROP) of the p-dioxanone monomer addressed the need for materials that could provide prolonged wound support while degrading safely in vivo. This innovation stemmed from the limitations of earlier absorbable sutures, such as catgut, which suffered from low tensile strength, unpredictable absorption rates, and heightened risks of infection due to tissue reactivity from its animal-derived collagen. The p-dioxanone monomer itself had been first synthesized and described in the scientific literature during the 1960s, enabling subsequent polymerization efforts. Ethicon's team, including Namassivaya Doddi, Charles C. Versfelt, and David Wasserman, advanced the ROP process using high-purity monomer (over 99%) and organometallic catalysts like diethyl zinc, followed by melt extrusion and orientation drawing to produce flexible monofilament fibers. A foundational patent, US 4,052,988, filed in 1976 and issued in 1977, detailed this method and highlighted PDO's potential for surgical devices, emphasizing its superior pliability compared to multifilament synthetic alternatives like polyglycolide, which were prone to degradation during sterilization. Pre-commercial testing in the focused on PDO's profile through animal implantation studies. In experiments with Long-Evans rats, subcutaneous implants of PDO fibers demonstrated approximately 70% mass loss by 120 days and complete resorption by 180 days, accompanied by minimal inflammatory response and no significant . These results confirmed PDO's and controlled , paving the way for its evaluation as a suture material capable of retaining strength longer than while avoiding its infection risks.

Key Milestones and Patents

The development of polydioxanone (PDS) as a biomedical material was marked by several pivotal advancements and regulatory milestones in the late and early . A foundational , US 4,052,988, was issued on October 11, 1977, to , Inc., describing synthetic absorbable surgical devices, including monofilament sutures, derived from polymers of p-dioxanone and related monomers like 1,4-dioxepan-2-one. This enabled the production of high-strength, bioabsorbable monofilaments with low tissue reactivity, setting the stage for PDS's commercial viability. International filings followed in the , facilitating global market entry. A major regulatory breakthrough occurred in 1981 when the U.S. Food and Drug Administration (FDA) approved the PDS suture under Premarket Approval (PMA) N18331, received on December 28, 1981, with a decision issued shortly thereafter on January 28, 1982, for use in soft tissue approximation. This approval, following the November 1981 granting of market clearance for the dissolving polydioxanone thread, represented the first commercial authorization for a monofilament PDS suture, enabling its initial clinical deployment in human surgery around 1981-1982. Early applications focused on general and ophthalmic surgery, with the suture's extended tensile strength (up to 6 weeks) proving advantageous for fascia closure and pediatric procedures. In the , innovations in PDS copolymers expanded its material properties and applications. For instance, Patent 5,868,788, issued on February 9, 1999, to Poly-Med, Inc., detailed high-strength, melt-processable copolymers rich in combined with p-dioxanone, offering improved flexibility and degradation profiles for surgical articles. These developments built on earlier work, such as 4,643,191 from on crystalline p-dioxanone- copolymers, and facilitated broader adoption in monofilament sutures with tailored absorption rates. By the 2000s, PDS expanded into orthopedic applications, with milestones including the clinical use of biodegradable PDS pins for fixation in surgeries, as documented in studies from 2001 evaluating resorption and imaging characteristics. This shift leveraged PDS's and complete resorption within 24 months, reducing the need for secondary removal surgeries in musculoskeletal repairs. Ethicon's robust portfolio on PDS, including the core monofilament , influenced competitive dynamics through licensing agreements and disputes in the absorbable suture market. For example, ongoing battles with competitors like United States Surgical Corporation in the 1990s and early underscored the protective role of PDS-related filings in maintaining market leadership.

Current Research Trends

Recent research on polydioxanone (PDO) has increasingly focused on enhancing its mechanical properties and through nanocomposites, particularly by incorporating (HA) nanoparticles into PDO matrices for bone tissue engineering applications. A 2023 study developed hybrid nanocomposites combining PDO with poly(lactide-co-caprolactone) and silane-modified HA nanoparticles, resulting in improved toughness, reduced inflammatory response , and enhanced osteoconductivity suitable for bone scaffolds. These 2020s investigations emphasize the role of surface-modified HA in promoting and mineralization while maintaining PDO's biodegradability, addressing limitations in load-bearing capacity for orthopedic implants. Advancements in additive manufacturing have enabled the 3D printing of PDO-based structures for personalized medical implants, allowing precise customization to anatomy. In a 2021 study, researchers fabricated a novel absorbable pancreaticojejunostomy device using a PPDO/ blend via , demonstrating controlled degradation over 12 weeks and reduced anastomotic complications in porcine models. Similarly, a 2022 investigation paired PDO membranes with 3D-printed scaffolds, achieving comparable bone regeneration outcomes to autologous grafts in calvarial defects, with PDO providing barrier functionality and hydrolytic stability. These developments highlight PDO's potential in patient-specific implants for and minimally load-bearing applications. Sustainability efforts in PDO research center on improving recyclability and exploring bio-derived modifications, alongside life-cycle analyses to quantify . A 2025 study synthesized recyclable PPDO-PLLA copolymers via chain extension, enabling chemical with minimal loss in mechanical properties and lower compared to virgin PDO production. Although p-dioxanone monomers remain predominantly petrochemical-derived, ongoing work investigates bio-based alternatives and blends to reduce reliance on fuels, with preliminary life-cycle assessments indicating up to 30% lower for degradable variants. Clinical trials since 2020 have evaluated PDO sutures in minimally invasive procedures, including , with a focus on prevention through antimicrobial modifications; for instance, 2024-2025 updates from repair trials show triclosan-coated PDO reducing surgical site s by 40-50% compared to uncoated versions, informing laparoscopic applications. Key challenges include accelerating PDO's for short-term implants, where low environments (below 1.67) have been shown to hasten by up to 5-fold in 2024 studies, enabling tunable resorption rates. coatings remain a priority, with 2025 research developing amoxicillin-loaded PDO membranes that curb formation in regenerative therapies, though and resistance concerns persist.