Hydrogel coated surgical meshes and uses thereof

Abstract

Described herein are hydrogel-coated surgical meshes and their use in hernia repair, reconstructive surgery, and other surgical procedures. In one aspect, the hydrogel-coated meshes comprise at least one antibiotic or antimicrobial agent for the treatment of hernia repair surgery. In one aspect, the hydrogel coated meshes provide localized, sustained antimicrobial activity for the treatment of surgical site infections. In one aspect, the hydrogel coated meshes provide localized, sustained prophylactic antimicrobial activity for the prevention of surgical site infections. In another aspect, the hydrogel coating may optionally include one or more additional therapeutic components, such as anti-inflammatory compounds or growth factors, to facilitate and enhance recovery following hernia repair, reconstructive procedures, or other surgeries.

Description

HYDROGEL COATED SURGICAL MESHES AND USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from United States patent applications 63 / 744,008 filed on January 10, 2025, and 63 / 784,630 filed on April 7, 2025, both of which are incorporated herein by reference in their entirety.TECHNICAL FIELD

[0002] The devices and methods of their use described herein relate to the field of biomedical devices, in particular surgical meshes, for the treatment of hernia repair surgeries, reconstructive procedures or other surgeries.BACKGROUND OF THE ART

[0003] Hernia repair is a widely performed surgical procedure that reinforces weakened or damaged abdominal wall tissues to prevent the protrusion of internal organs. Uncoated surgical meshes, commonly used in both open and laparoscopic hernia repairs, have significantly improved outcomes by providing essential structural support.

[0004] Nevertheless, to build upon the success of hernia repairs, advancements in surgical mesh technology have sought to address the limitations of traditional uncoated meshes. While uncoated surgical meshes provide effective reinforcement, they are often associated with complications such as inflammation, tissue adhesion, and infection, particularly in complex or high-risk cases. In response, coated surgical meshes have been developed, incorporating advanced materials and therapeutic agents to enhance biocompatibility, reduce complications, and promote better patient recovery.

[0005] Surgical site infections (SSIs) represent a persistent and significant challenge not just for hernia repairs but other surgeries as well. Standard prophylactic measures, including systemic administration of antibiotics such as cefazolin, have reduced but not eliminated infection rates, particularly in clean-contaminated and contaminated surgical fields. The Ariste® AB Mesh, an approved surgical implant designed for hernia repair, incorporates antibiotics such as minocycline and rifampin to reduce the risk of microbial colonization during implantation. However, the Ariste® AB Mesh exhibits a limited drug loading capacity of about 171 pg / cm2, with antimicrobial protection largely limited to the early postoperative period.

[0006] While some surgical meshes have been modified intraoperatively via antibiotic soaking, the lack of widely available, pre-manufactured surgical meshes with durable and sustained-release antibiotic coatings continues to hinder efforts to fully mitigate infection risks associated with implantable materials.

[0007] These limitations, combined with persistent surgical site infection rates, concerns about antibiotic resistance, and inadequate prevention of biofilm formation, underscore the need for next generation meshes capable of delivering extended, clinically meaningful infection control, particularly in high-risk or contaminated surgical fields.SUMMARY

[0008] Certain embodiments provide for a hydrogel coated surgical mesh comprising: (1) a biocompatible mesh matrix, and (2) a hydrogel polymer composition; said hydrogel polymer composition comprising (a) an anionic gelling polymer, (b) an inverse thermal gelling polymer, and (c) a therapeutically effective amount of a therapeutic component wherein said mesh matrix is coated with said hydrogel polymer composition.

[0009] In certain embodiments, the surgical mesh matrix comprises a synthetic polymer. In certain embodiments, the synthetic polymer may be a non-biodegradable polymer. In certain embodiments, the synthetic polymer is a biodegradable polymer. In certain embodiments, the surgical mesh matric comprises a natural polymer.

[0010] In certain embodiments, the hydrogel polymer composition is a solid gel at room temperature, experiences shear thinning when subjected to applied pressure (e.g., during injection), and reverts to a solid gel once the pressure is removed.

[0011] In certain embodiments, the anionic gelling polymer is hyaluronan (HA) or a salt thereof (e.g., sodium hyaluronan) and the inverse thermal gelling polymer is methylcellulose (MC).

[0012] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 0.5% (wt / wt)-3% (wt / wt) hyaluronan (HA), 0.5% (wt / wt)-8% (wt / wt) methylcellulose (MC) and a therapeutic component.

[0013] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 1:1 (wt / wt) ratio of HA:MC.

[0014] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 1.4:2 (wt / wt) ratio of HA:MC.

[0015] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 2:3 (wt / wt) ratio of HA:MC.

[0016] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 2:7 (wt / wt) ratio of HA:MC.

[0017] In certain embodiments, the therapeutic component may be selected from the group consisting of an anti-inflammatory agent, an angiogenesis promoter, anti-microbial agent, and any combination thereof.

[0018] In certain embodiments, the hydrogel polymer composition comprises a therapeutically effective amount of a therapeutic component comprising a therapeutic agent having a first form, which is more soluble in the hydrogel polymer composition, and a second form, which is less soluble in the hydrogel polymer composition, wherein in physiological conditions the first form is released from the hydrogel polymer composition more quickly than the second form, which has a more extended release. In certain embodiments, the therapeutic component is selected from an anti-inflammatory agent, an angiogenesis promoter, an antimicrobial agent, and any combination thereof; in some embodiments, these are the sole active therapeutic agents in the hydrogel polymer composition. In some embodiments, an antimicrobial or a combination of antimicrobials are present as the sole active therapeutic agent(s) in the hydrogel polymer composition. In certain embodiments, the therapeutic agent is not a local anesthetic agent.

[0019] In certain embodiments, the hydrogel polymer compositions described herein comprise at least one antibiotic. The antibiotic may be selected from any antibiotic and may include one or more antibiotics individually or in combination, without limitation to the specific examples provided herein.

[0020] In certain embodiments, the at least one antibiotic agent is present in both its acidic and basic form.

[0021] In certain embodiments, the hydrogel coated surgical meshes described herein provide for an immediate release of the antibiotic agent and a controlled release of the antibiotic agent.

[0022] In certain embodiments, the hydrogel coated surgical meshes described herein provide for a continuous release of the antibiotic agent for at least 12 hours, at least 24 hours, at least 48 hours or at least one week at physiological conditions.

[0023] In some embodiments, the therapeutic component comprises two or more antibiotic agents, each having a different release profile and spectrum of antibiotic action.

[0024] In certain embodiments, the hydrogel coated surgical meshes described herein are configured to control or prevent infection and / or facilitate and enhance recovery following hernia repair, reconstructive procedures or other surgeries.

[0025] Certain embodiments provide for a method of treating a hernia in a patient comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component. In some embodiments the therapeutic component may be selected from the group consisting of an anti-inflammatory agent, an angiogenesis promoter, an antimicrobial agent, and any combination thereof. In certain embodiments, the antimicrobial agent is an antibiotic agent. In some embodiments, the therapeutic component is not a local anesthetic.

[0026] Certain embodiments provide for a method of treating surgical site infections in a patient, optionally a patient treated for hernia, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the surgical site, in one embodiment a hernia site, and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent, in one embodiment, an antibiotic agent. Optionally, in some embodiments, the antimicrobial agent may be combined with an anti-inflammatory agent, an angiogenesis promoter, a further antimicrobial, and any combination thereof. Certainembodiments provide for the method of prophylactically preventing surgical site infections in a subject.

[0027] Certain embodiments provide for a method of manufacturing a surgical mesh comprising: (a) providing a biocompatible matrix; (b) coating the biocompatible matrix with a hydrogel polymer composition comprising: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antibiotic agent; and (c) drying the hydrogel polymer coating. In some embodiments, the hydrogel polymer coating is dried for at least 20 hours, optionally at a temperature of between 30°C and 45°C. Optionally, prior to drying the hydrogel polymer coating is incubated at a temperature of between 1 °C and 4°C for a period of 2 and 6 hours. In some embodiments, the method further comprises physically blending the anionic gelling polymer and the inverse thermal gelling polymer and dispersing the at least one antibiotic agent therein. Optionally, in some embodiments, the hydrogel polymer composition further includes an anti-inflammatory agent, an angiogenesis promoter, an antimicrobial other than an antibiotic agent and any combination thereof.

[0028] Certain embodiments contemplate kits and pharmaceutical packages comprising the hydrogel coated surgical meshes described herein.

[0029] The above summary of the embodiments described herein is not intended to describe each disclosed embodiment or every implementation of the hydrogel coated surgical meshes described herein. The description that follows more particularly exemplifies illustrative embodiments. In several places throughout the description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.BRIEF DESCRIPTION OF THE DRAWINGS

[0030] All composition numbers shown in the drawings and mentioned in the following descriptions of the drawings correspond to the compositions detailed in Table 1.

[0031] FIGURE 1 is a graph illustrating the antibiotic loading capacity of Composition 1 (vancomycin), Composition 2 (erythromycin), Composition 3 (tetracycline), and Composition 4 (cefazolin) applied to Phasix™ surgical meshes, as described in Example 1. The coatings delivered greater than 3.3 mg / cm2of each antibiotic, corresponding to a total loading of 500mg on a 10 x 15 cm mesh. Notably, antibiotic loading levels remained consistent before and after mechanical bending of the coated meshes, demonstrating the durability and retention of the antibiotic within the hydrogel coating under mechanical stress.

[0032] FIGURE 2 illustrates the release profiles of vancomycin, erythromycin, and tetracycline from Phasix™ surgical meshes coated with Composition 1 (vancomycin), Composition 2 (erythromycin), Composition 3 (tetracycline), and Composition 4 (cefazolin) respectively.

[0033] FIGURE 3 comprises Figure 3A, Figure 3B, and Figure 3C. Figure 3A illustrates the antibacterial activity of a resorbable surgical mesh (Phasix®) coated with Composition 1. The figure demonstrates a zone of inhibition assay performed against Staphylococcus aureus. The Phasix® mesh coated with Composition 1 displays a clear zone of bacterial growth inhibition surrounding the mesh, indicating effective local antibiotic release and antimicrobial activity. In contrast, uncoated Phasix® mesh (Figure 3B) or Phasix mesh coated with HAMC alone (Figure 3C) shows no inhibition zone, confirming that the antibacterial effect is attributable to the release of vancomycin from Composition 1.Arrowhead points to the piece of mesh in Figure 3B and Figure 3C, which did not inhibit the growth of S. aureus. This result supports the utility of Composition 1 for prophylactic infection control in implantable mesh applications.DETAILED DESCRIPTION

[0034] The following detailed description is provided to aid those skilled in the art in practicing the present disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0035] The numerical values specified throughout this disclosure including the claims, are stated as approximations as though the numerical values are preceded by the word “about” unless expressly stated otherwise. Similarly, where a range of numeric values are specified, the minimum and maximum values of the range as well as all values within the range are stated as approximations as though preceded by the word “about” unless expressly stated otherwise. In this manner, the term “about”, “approximately”, and “comparable to” when used in reference to a particular recited value, means there can be an acceptable variation range, as determined by one of ordinary skill in the art to which this disclosure pertains. For example, in some embodiments, the terms "about," “approximately,” and “comparable to” may encompass a range of values within 25%, 24%, 23%, 22%, 21%,20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less of the referred value. Also, the disclosure of ranges is intended as a continuous range including every value between the minimum and maximum values recited as well as any ranges that can be formed by such values. Also, disclosed herein are all ratios (and ranges of any such ratios) that can be formed by dividing a recited numeric value into any other recited numeric value. Accordingly, the skilled person will appreciate that many such ratios, ranges, and ranges of ratios can be unambiguously derived from the numerical values presented herein and, in all instances, such ratios, ranges, and ranges of ratios represent various embodiments of the present invention.

[0036] The term “and / or” means one or all the listed elements or a combination of any two or more of the listed elements.

[0037] The term “therapeutic component” refers to a component of the hydrogel polymer composition that comprises one or more therapeutic agents, which may be of the same or different class, and which provide a therapeutic, prophylactic, or biological effect when delivered to a subject. The therapeutic component may include a single therapeutic agent or a combination of therapeutic agents and may optionally include agents that act additively or synergistically. In certain embodiments, the therapeutic component comprises one or more agents selected from anti-inflammatory agents, angiogenesis promoters, antimicrobial agents, and any combination thereof. In some embodiments, the therapeutic component does not include a local anesthetic. The therapeutic component may be incorporated into the hydrogel polymer matrix in an amount sufficient to achieve local therapeutic concentrations at the site of implantation while maintaining the structural and rheological properties of the hydrogel polymer composition.

[0038] As used herein, the terms “treatment”, “treating”, “treat”, or the like refer to an approach for obtaining beneficial or desired results, including therapeutic, prophylactic, or clinical results. Beneficial or desired clinical results may include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of disease stabilization of a disease state (i.e., not worsening), preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also include prophylactic intervention, such as reducing the likelihood that a condition will develop or recur relative to the expected outcome in the absence of treatment. Accordingly, the use of the biocompatible hydrogel-coated surgical meshes described herein may reduce the severity, extent, or consequences of a disease or physiological disorder, but need notabolish every manifestation of such disease or disorder to constitute an effective therapeutic or prophylactic intervention. Thus, “treatment” with the hydrogel-coated surgical meshes described herein need not effect a complete cure or eradicate every symptom or manifestation of a disease to constitute a viable therapy.

[0039] As used herein, “therapeutically effective amount” refers to an amount effective, at dosages and for a particular period of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of the therapeutic component may vary according to factors such as the disease state, age, sex, and weight of the subject, and the ability of said therapeutic component to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of said drugs are outweighed by the therapeutically beneficial effects.

[0040] The term “pharmaceutically acceptable salt” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by methods known in the art.

[0041] As used herein, “biocompatible” means substantially free from deleterious effects on living systems or tissues. In surgery contexts, “biocompatible” means substantially free from inducing a serious rejection reaction.

[0042] As used herein, “coating” and grammatical variations thereof refer to a substance applied to the surface of a substrate e.g. a mesh matrix. While a coating is applied to a surface of the substrate, it may, in some embodiments, penetrate, at least in part, into the substrate. Further, a coating may be applied to all or only part of the substrate e.g. only one side of a mesh may be coated while the other side may be left uncoated.

[0043] The words “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the invention.

[0044] As used herein, “subject” or “patient” are used interchangeably and refer to an animal being treated using a device (mesh), kit or method provided herein, in some embodiments, a mammal, which may be a human, domestic livestock, or a companion animal. In certain embodiments, the subject or patient is a human. Unless context dictates otherwise, a human subject or patient can be a pediatric, adult, or a geriatric subject, and can be of any gender.

[0045] As used herein, the term “kit” refers to an assembly of two or more components provided together typically for coordinated use. In certain embodiments, a kit may comprise the hydrogel-coated mesh or components thereof and one or more additional items, such as a therapeutic component, a diluent, a syringe, an applicator, or instructions for use.

[0046] As used herein, the term “package” refers to a physical container or packaging system in which a product is provided for storage, handling, or distribution. A package may contain, for example, a single hydrogel-coated mesh and instructions for use.

[0047] Management and prevention of bacterial infection during hernia surgery recovery remain significant challenges, as current treatment strategies often fail to fully address patient needs.

[0048] The coated surgical meshes provided herein address one or more of these shortcomings, in that they can advantageously provide one or more of antimicrobial benefits, infection control, and promoting optimal tissue integration, while maintaining the mesh’s structural integrity and biocompatibility.

[0049] The management of surgical site infections (SSIs) in hernia surgery recovery remains suboptimal, despite prophylactic antibiotic administration and aseptic surgical techniques. Systemic antibiotics, often administered preoperatively and continued postoperatively, rely on sufficient vascular perfusion to reach the surgical site in effective concentrations. However, in avascular or poorly perfused tissues surrounding implanted meshes, antibiotic penetration is often inadequate, leaving areas vulnerable to bacterial colonization and biofilm formation. Biofilms, complex communities of bacteria encased in an extracellular matrix, exhibit high resistance to both antibiotics and immune clearance, making established infections difficult to eradicate. Current antibiotic-coated meshes aim to address this issue by providing localized antimicrobial activity, but their limited drug loading capacity and rapid elution kinetics can reduce their long-term efficacy. Additionally, reliance on conventional systemic antibiotics raises concerns about antimicrobial resistance, furtherlimiting treatment options. Compounding these challenges, current approaches often do not adequately address critical aspects of recovery, such as reducing inflammation or preventing bacterial infections at the surgical site, both of which are essential for optimal outcomes. These challenges underscore the urgent need for next-generation strategies that can achieve sustained, broad-spectrum infection prevention ultimately improving patient recovery outcomes.

[0050] Advantageously, embodiments of the hydrogel coated surgical meshes provided herein can deliver an immediate release followed by a sustained release of an antimicrobial for treating (including preventing) post-surgical infection while minimizing risks and addressing the broader complexities of hernia surgery recovery.

[0051] As used herein, the term “antimicrobial agent” refers to any compound, molecule, salt, derivative, prodrug, or combination thereof that exhibits activity against bacteria, fungi, viruses, or other pathogenic microorganisms. The antimicrobial agent may be present in the hydrogel in a free acid form, free base form, salt form, or any combination thereof, including mixtures of acidic and basic forms to modulate solubility and release kinetics.

[0052] In certain embodiments, the antimicrobial agent is selected from antibiotics, including but not limited to p-lactams (e.g., penicillin G, ampicillin, amoxicillin, cefazolin, cephalexin, ceftriaxone, meropenem, imipenem, aztreonam), glycopeptides and lipoglycopeptides (e.g., vancomycin, teicoplanin, dalbavancin, oritavancin), macrolides (e.g., erythromycin, azithromycin, clarithromycin), tetracyclines (e.g., tetracycline, doxycycline, minocycline), aminoglycosides (e.g., gentamicin, tobramycin, amikacin), fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin), folate pathway inhibitors (e.g., trimethoprim, sulfamethoxazole), oxazolidinones (e.g., linezolid, tedizolid), lincosamides (e.g., clindamycin, lincomycin), and other antibiotic classes such as rifamycins (e.g., rifampin), nitroimidazoles (e.g., metronidazole), and polypeptide antibiotics (e.g., bacitracin).

[0053] In other embodiments, the antimicrobial agent comprises an antifungal compound, including but not limited to amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, nystatin, terbinafine, or an echinocandin such as caspofungin, micafungin, or anidulafungin.

[0054] In certain embodiments, the antimicrobial agent comprises a non-antibiotic or broadspectrum antimicrobial, such as chlorhexidine, povidone-iodine, benzalkonium chloride, hydrogen peroxide, silver ions or silver nanoparticles, ortriclosan.

[0055] In some embodiments, the antimicrobial agent includes antimicrobial peptides, including but not limited to LL-37, defensins, cathelicidins, nisin, or polymyxins such as colistin. In some embodiments, the anti-microbial agent is a non-peptide antimicrobial.

[0056] In certain embodiments, the therapeutic component comprises a combination of two or more antibiotic agents. The hydrogel polymer composition coatings described herein provide several advantages for incorporating and delivering combinations of antibiotics as compared to traditional uncoated surgical meshes or other polymeric coatings.

[0057] The hydrogel polymer compositions, comprising an anionic gelling polymer (e.g., hyaluronan) and an inverse thermal gelling polymer (e.g., methylcellulose), forms a hydrated, three-dimensional network capable of accommodating significantly higher drug loading than many polymeric coatings. Without wishing to be bound by theory, it is believed that the physicochemical architecture of said hydrogel polymer coatings with its tunable porosity, ionic interactions, and thermoresponsive viscosity, allows simultaneous incorporation of antibiotics of different charge states, solubilities, and molecular weights. As a result, the hydrogel polymer compositions can support broad-spectrum antibiotic combinations, including mixtures of acidic and basic forms of antibiotics.

[0058] The use of multiple antibiotic agents within the hydrogel polymer coatings may provide synergistic or additive antimicrobial effects. Surgical site infections often involve polymicrobial populations, including Gram-positive, Gram-negative, and anaerobic bacteria. By incorporating two or more antibiotics with complementary mechanisms of action or activity spectra, the coated mesh can provide enhanced prophylaxis against a wider range of pathogens. In addition, combination antibiotic therapy may reduce the likelihood of bacterial resistance emerging at the implantation site due to multi-target antimicrobial pressure.

[0059] In some embodiments, the hydrogel polymer compositions enable differential release of the antibiotic agents based on their ionic charge, molecular size, or affinity for the hydrogel components. This allows for immediate release of one antibiotic (e.g., to rapidly sterilize the site) combined with sustained release of another antibiotic (e.g., to prevent biofilm formation over time). The ability to tailor release kinetics for each antibiotic within a combination provides superior infection-control performance compared to single-agent systems.

[0060] The hydrogel polymer compositions can release the antibiotic agent(s) present in acidic and basic forms simultaneously, allowing combination regimens that would otherwise be chemically incompatible in a single formulation. This includes combinations such as cefazolin (acidic form) with erythromycin, vancomycin, tetracycline, or other antibiotic classes. As a result, the platform enables formulation of antibiotic pairs that traditionally require separate dosage forms.

[0061] Accordingly, in certain embodiments, the therapeutic component comprises at least two antibiotic agents selected from different mechanistic or structural classes, including but not limited to p-lactams, glycopeptides, macrolides, tetracyclines, aminoglycosides, oxazolidinones, quinolones, lincosamides, or combinations thereof. In some embodiments, the combination comprises (i) a first antibiotic in an acidic form and (ii) a second antibiotic in a basic form, each present in a ratio configured to provide immediate and sustained antimicrobial activity.

[0062] In various embodiments, the therapeutic component is present at 1% to 30% (wt / wt), preferably 1% to 20% of the hydrogel polymer composition. In some embodiments, the therapeutic component is present at 2% to 18%, 3% to 15%, 5% to 15% (wt / wt) or 6 to 8% of the hydrogel polymer composition. In certain embodiments, the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition. In some embodiments, the therapeutic component is present at 8% to 12%, 10% to 15%, or 5% to 10% (wt / wt) of the hydrogel polymer composition.

[0063] In certain embodiments, the hydrogel polymer matrix is capable of accommodating relatively high loading levels of therapeutic components without precipitation, phase separation, or compromise of the coating’s adhesion to the surgical mesh. The hyaluronanmethylcellulose network can retain therapeutic components through hydrogen bonding, ionic interactions, hydrophobic interactions, or a combination thereof, thereby enabling uniform distribution of the therapeutic component throughout the hydrogel matrix.

[0064] In some embodiments, the total therapeutic component comprises a combination of antibiotic agents, anti-inflammatory agents, angiogenesis promoters, or any two or all three classes of therapeutic agents. In such embodiments, each therapeutic agent may independently be present at 1% to 15% (wt / wt), or the combined therapeutic loading may total 3% to 30% (wt / wt) of the hydrogel polymer composition.

[0065] In certain embodiments, increasing the loading of one or more therapeutic components within the disclosed ranges may proportionally enhance local delivery, modify the release profile, or contribute synergistically to the therapeutic effect while maintaining acceptable hydrogel performance.

[0066] Accordingly, certain embodiments described herein provide for a hydrogel coated surgical mesh comprising: (1) a biocompatible mesh matrix, and (2) a hydrogel polymer composition; said hydrogel polymer composition comprising (a) an anionic gelling polymer, (b) an inverse thermal gelling polymer, and (c) a therapeutically effective amount of a therapeutic component; wherein said mesh matrix is coated with said hydrogel polymer composition and the therapeutic component comprises at least one antimicrobial agent, preferably an antibiotic agent.

[0067] In certain embodiments, the hydrogel polymer composition provides for an immediate release followed by a sustained release of an antimicrobial agent, preferably an antibiotic, at physiological conditions, optionally in combination with release of a therapeutic component selected from the group consisting of an anti-inflammatory agent, an angiogenesis promoter, or any combination thereof. In one embodiment, the hydrogel polymer composition comprises the antimicrobial, preferably an antibiotic, in a salt form and in a basic form. In certain specific embodiments, the hydrogel polymer composition coating the biocompatible surgical mesh matrix comprises a mixture of an antimicrobial, preferably an antibiotic, and a pharmaceutically acceptable salt and / or salts of said antimicrobial, and optionally a therapeutic component selected from the group consisting of an antiinflammatory agent, an angiogenesis promoter, an antimicrobial agent other than an antibiotic agent or any combination thereof.

[0068] In certain embodiments, the hydrogel coated surgical meshes are flexible and maintain consistent release profiles under bending stress, folding, torsion, or other mechanical deformation typically encountered during surgical handling and placement. The hydrogel polymer coating may retain the therapeutic component within the hyaluronanmethylcellulose network through ionic interactions, hydrogen bonding, hydrophobic interactions, or physical entrapment, thereby reducing undesired loss of therapeutic agent during manipulation. The distortions resulting from body movements can potentially alter the integrity and functionality of a coated mesh, impacting the release profile of the therapeutic component within a coating of the mesh. By demonstrating that the HAMC hydrogel polymer coating composition maintains consistent release profiles even under bending stress in the examples below, the data highlights the robustness and reliability of the surgical meshesdescribed herein. This property is important in scenarios where the mesh must withstand physical manipulation or dynamic in vivo environments without compromising its therapeutic efficacy.

[0069] In some embodiments, bending of the hydrogel-coated surgical mesh results in no more than 20% loss of the therapeutic component from the hydrogel polymer composition. In various embodiments, the loss of therapeutic component during bending is no more than 15%, no more than 10%, no more than 8%, no more than 5%, or no more than 2% of the total therapeutic component initially loaded into the hydrogel polymer composition. In certain embodiments, the therapeutic component loss during bending is less than 20%, less than 10%, less than 5%, or less than 2%.

[0070] In some embodiments, the hydrogel coating is formulated to minimize drug displacement or shedding during mechanical deformation, thereby preserving the intended release profile and ensuring that therapeutic dosing at the surgical site remains within the desired therapeutic window.

[0071] Coating surgical meshes with therapeutics presents several challenges, including ensuring uniform adhesion, maintaining the stability of a therapeutic component during the drying process, and achieving predictable and sustained release profiles.

[0072] Various techniques have been explored to apply antibiotics directly to mesh surfaces. For example, plasma-induced polymer grafting approaches have been investigated to covalently bond antimicrobial agents onto mesh surfaces. However, these methods may result in heterogeneous coatings, impair the mechanical flexibility of the mesh, and complicate manufacturing processes. Similarly, polymer-based coatings such as PLGA-antibiotic systems often suffer from burst release kinetics and localized acidosis due to polymer degradation, potentially delaying healing and exacerbating inflammation.

[0073] In certain embodiments, the HAMC hydrogel polymer compositions described herein are readily applied to the surgical mesh matrix, ensuring uniform coverage and consistent therapeutic loading, and they can be dried without compromising the stability or activity of a therapeutic component, simplifying storage and handling. Additionally, the hydrogel polymer composition comprising HAMC enables controlled and sustained release profiles, even under mechanical stress or dynamic conditions, which is important for maintaining therapeutic efficacy.

[0074] In certain embodiments, the anionic gelling polymer may be selected from hyaluronan (HA), derivatives of hyaluronan, alginate, derivatives of alginate, carboxymethyl cellulose (CMC), carboxyethyl cellulose (CEC), derivatives of hydroxypropyl cellulose (HPC), derivatives of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl methyl cellulose phthalate (HPMCP), sodium carboxymethyl cellulose (Na-CMC), phosphorylated cellulose, sulfated cellulose, acrylates, C10-30 alkyl acrylate cross polymer, carbomer, polyacrylic acid (PAA), poly(methacryclic acid) and mixtures thereof. It will be apparent to the skilled artisan that HPC and HPMC are not inherently anionic but can be chemically modified to introduce anionic groups, such as carboxyl or sulfonate groups, which would make them anionic.

[0075] In certain embodiments, the molecular weight of the anionic gelling polymer may be between 100,000 Da and 7,000,000 Da. In further embodiments, the anionic gelling polymer comprises or is hyaluronan or a salt or derivative thereof (e.g., sodium hyaluronan).

[0076] In certain embodiments, hyaluronan is the anionic gelling polymer.

[0077] Hyaluronic acid (or hyaluronan) (HA) is a linear polysaccharide composed of repeating disaccharide units of N-acetyl-glucosamine and D-glucuronic acid. HA is degraded enzymatically by hyaluronidase, which can be produced by cells. Its polymeric chains, of lengths of 10-15 thousand disaccharides, form random coils with large spheroidal hydrated volumes of up to 400-500 nm in diameter. Reactions can occur at the carboxyl group or the hydroxyl group of HA and also at the amino group when the N-acetyl group is removed.

[0078] Pharmaceutical grade HA is available in a wide variety of molecular weights, in the range of between 100,000 g / mol and 3,000,000 g / mol. In one embodiment the composition comprises HA in the range of 500,000 g / mol and 2,500,000 g / mol, in one embodiment in the range of 1,000,000 g / mol and 2,000,000 g / mol, and in a further embodiment in the range of 1,400,000 g / mol to 1,600,000 g / mol.

[0079] The hydrogel polymer compositions described herein, comprising hyaluronic acid (HA) and methylcellulose (MC), leverage the shear-thinning properties of the anionic gelling polymer component (HA). These properties enable the hydrogel polymer compositions to rapidly recover its original viscosity and solid gel state after shearing, achieving this restoration more quickly than an inverse thermal gelling polymer alone.

[0080] In certain embodiments, the inverse thermal gelling polymer may be selected from methylcellulose, a chitosan and p-glycerophosphate solution, collagen, tri-blockcopolymer of polyethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol), tri-block copolymer of polypropylene glycol)-poly(ethylene glycol)-poly (propylene glycol), poly(N-isopropyl acrylamide), agarose, copolymers of poly-N-isopropylacrylamide, polysaccharides and mixtures thereof.

[0081] In certain embodiments, the molecular weight of the inverse thermal gelling polymer may be between 2,000 Da and 1,000,000 Da.

[0082] In certain embodiments, the inverse gelling thermal polymer component of the hydrogel polymer composition is methylcellulose (MC). In certain embodiments, the MC has a viscosity greater than 400cP. In certain embodiments, the MC has a viscosity of 2800cP. MC is an example of a temperature sensitive gel, or a thermally reversible gel, that gels upon an increase in temperature. When the degree of substitution of hydroxyl groups with methyl groups is between 1.4 and 1.9 per monomer unit, MC has inverse thermal gelling properties. As the temperature increases, the methyl groups of MC form hydrophobic interactions and water molecules are released from interacting with MC, thereby forming a gel.

[0083] The MC may have a molecular weight in the range of between 2,000 g / mol and 1,000,000 g / mol. In one embodiment the composition comprises MC in the range of 10,000 g / mol and 500,000 g / mol, in one embodiment in the range of 100,000 g / mol to 400,000 g / mol, and in one embodiment in the range of 200,000 g / mol to 300,000 g / mol.

[0084] Blends of unmodified HA with a gelling polymer, such as MC, are injectable upon an application of force to a syringe because the shear-thinning properties of HA cause the polymer chains to straighten and align themselves, permitting flow through the needle. HA then returns to its high viscosity, zero shear structure upon exiting the needle as the polymeric chains once again become entangled amongst themselves.

[0085] In certain embodiments, the hydrogel polymer compositions described herein may comprise, consist or consist essentially of the HAMC gel polymer mixture, a therapeutic component, such as an antimicrobial agent, water and biocompatible buffers and / or salts, which may include disodium hydrogen phosphate, sodium phosphate, sodium chloride, potassium chloride, potassium phosphate, and / or potassium dihydrogen phosphate. For example, the constituents of the hydrogel polymer composition may be an HAMC gel polymer in an amount as taught herein, water and biocompatible buffers and / or salts, and 1-20 wt% of an antimicrobial based on the total weight of the composition; and e.g. thecomposition may include 0.5 to 1.5 wt% of an acid addition salt of the local antimicrobial and 18.5 to 19.5 wt% of free-base particles of the antimicrobial based on the total weight of the composition .

[0086] The hydrogel polymer compositions described herein may be combined with any pharmaceutically acceptable carrier or excipient. As used herein, a “pharmaceutically acceptable carrier” or “excipient” can be a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle selected to facilitate delivery of a therapeutic component to a subject. The excipient may be liquid or solid. Examples of pharmaceutically acceptable carriers include one or more of water, saline, phosphate buffered saline, glycerol, ethanol and the like, as well as combinations thereof.Pharmaceutically acceptable carriers may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the pharmacological agent.

[0087] In some embodiments, the pharmaceutically acceptable carrier is phosphate buffered saline or saline.

[0088] The hydrogel polymer compositions as described herein may suitably be prepared through the physical blending of HA and MC in saline. After MC and HA are dispersed in saline and allowed to dissolve, a therapeutic component, preferably but not necessarily an antimicrobial, suitably in particle form, may be dispersed in HAMC. The compositions may be sterilized by autoclave, gamma sterilization, steam sterilization or filter sterilization. Compositions are suitably stored at a range of 4° C to room temperature (25° C). Methods of manufacturing the injectable hydrogel polymer matrix formulations described herein are described for example in US patent 9,205,046 which is incorporated herein by reference in its entirety.

[0089] In certain embodiments, the hydrogel comprises a suitable antibiotic agent which may comprise both an acidic form and a basic form to achieve a biphasic or sustained-release antimicrobial profile. Antibiotics suitable for use in dual-form combinations include, without limitation, antibiotics possessing ionizable functional groups that permit formulation as both free acids / bases or pharmaceutically acceptable salts. The acidic or salt form of the antibiotic provides rapid dissolution upon implantation, delivering an immediate antimicrobial effect during the perioperative period, while the corresponding basic or free-base form exhibits reduced solubility and slower elution from the hydrogel matrix, thereby maintaining prolonged local concentrations sufficient to inhibit microbial growth and biofilm formation.Incorporating both forms within the same hydrogel coating allows controlled modulation of release kinetics, improved infection prophylaxis, and extended antimicrobial activity over clinically relevant timeframes.

[0090] In certain embodiments, the hydrogel compositions can optionally include a therapeutic component other than antimicrobials such as for example anti-inflammatory agents and promoters of angiogenesis. Examples of anti-inflammatory agents include, but are not limited to dexamethasone, prednisolone, triamcinolone acetonide, ketorolac, ibuprofen, celecoxib, tacrolimus, pirfenidone, lnterleukin-1, curcumin, resveratrol, and pharmaceutically acceptable salts and combinations thereof.

[0091] Examples of angiogenesis promoters include but are not limited to vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDFGF), angiopoietin Ang-1, angiopoietin Ang-2, lnterleukin-8 (IL-8) , granulocytemacrophage colony-stimulating factor (GM-CSF), collagen, heparin, thalidomide derivatives, prostaglandin E1 (PGE1), dimethyloxalyglycine (DMOG), exosomes from mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), angiomodulin, erythropoietin, and any combination thereof.

[0092] In certain embodiments, the hydrogel coated surgical meshes described herein comprising at least one antimicrobial agent, provide for an immediate release followed by a sustained release of the antimicrobial agent for at least 12 hours, at least 24 hours, at least 48 hours or at least one-week post-surgery at physiological temperature.

[0093] In certain embodiments, no more than 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, or 20%, of the therapeutic component is released from the hydrogel coated surgical meshes within 24 hours of application of the hydrogel coated surgical mesh at the site of surgery at physiological temperature. In certain embodiments, the therapeutic component is an antimicrobial agent. In certain embodiments, the antimicrobial agent is an antibiotic agent.

[0094] In certain embodiments in which the hydrogel-coated surgical mesh comprises an antimicrobial agent, such as an antibiotic, the hydrogel coating is configured to provide rapid release of the antimicrobial agent following application at the site of surgery. In various embodiments, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or up to 100% of the antimicrobial agent is released within 24 hours of application. In some embodiments, no more than 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% of theantimicrobial agent is released within the first hour, and no more than 80%, 85%, 90%, or 95%, is released within the first 3 hours following application. In certain embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the antimicrobial agent is released within 6 hours. In some embodiments, substantially complete release (e.g., at least 95%, at least 98%, or 100%) is achieved within 24 hours. In all such embodiments, the release profile is configured to provide an early, high-concentration bolus of antimicrobial agent to the surgical site to reduce bacterial burden shortly after implantation of the hydrogel-coated mesh.

[0095] In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 0.5% (wt / wt)-3% (wt / wt) hyaluronan (HA), 0.5% (wt / wt)-8% (wt / wt) methylcellulose (MC) and a therapeutic component. In certain embodiments the hydrogel polymer composition coating the surgical mesh matrix comprises 1% (wt / wt)-2% (wt / wt) HA, 1% (wt / wt)-7% (wt / wt) MC and a therapeutic component. In certain embodiments the hydrogel polymer composition coating the surgical mesh matrix comprises 1% (wt / wt)-1% (wt / wt) (1:1 weight ratio) HA:MC and a therapeutic component. In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 1.4% (wt / wt)-2% (wt / wt) (1.4:2 weight ratio) HA:MC and a therapeutic component. In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 2% (wt / wt)-3% (wt / wt) (2:3 weight ratio) HA:MC and a therapeutic component. In certain embodiments, the hydrogel polymer composition coating the surgical mesh matrix comprises 2% (wt / wt)-7% (wt / wt) (2:7 weight ratio) HA:MC and a therapeutic component. In certain embodiments, the pH of the HAMC hydrogel polymer composition is from 6.5 to 9.5. Certain embodiments of the hydrogel polymer compositions have been described in for example, US patent nos.7,767,656; and 9,205,046; the contents of which are incorporated herein by reference in their entirety.

[0096] The form and amount of the therapeutic component dispersed within the hydrogel polymer matrix can be set based on several factors, including the specific therapeutic component used, the desired release profile, the condition being treated, the severity of the condition being treated, the size of the surgical mesh, the duration of treatment required, the type of subject (e.g., human or animal), gender of the subject, and the physiological characteristics of the subject. Accordingly, in certain embodiments, the therapeutic component may be present from 1% (wt / wt)-20% (wt / wt) of the hydrogel polymer composition coating. In certain embodiments, the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition. In certain embodiments, thetherapeutic component is an antimicrobial agent. In certain embodiments, the antimicrobial agent is an antibiotic.

[0097] In certain embodiments, the therapeutic component may comprise one or more therapeutic agent(s) in combination with the antibiotic agent. The type and amount of the other therapeutic agent in the hydrogel polymer composition will depend on the condition being treated and the severity of the condition being treated. The additional therapeutic agent may be selected from an anti-inflammatory agent, an angiogenesis promoter, a nonantibiotic antimicrobial agent, and any combination thereof providing the other therapeutic agent(s) is not contraindicated. In certain embodiments, the additional therapeutic agent may be a second antibiotic agent that is different from the original antibiotic agent providing the two different antibiotics are not contraindicated. For example, if the original antibiotic agent is cefazolin, the second antibiotic agent may be any antibiotic other than cefazolin providing the second antibiotic agent is not contraindicated and does not create any safety or toxicity issues. The amount of the additional therapeutic agent can vary based on several factors, including the condition being treated, the severity of the condition being treated, the desired release profile, the size of the surgical mesh, the duration of treatment required, the type of subject (e.g., human or animal), gender of the subject, and the physiological characteristics of the subject.

[0098] Specific hydrogel polymer compositions comprising hyaluronan, methylcellulose and an antibiotic are provided in Table 1. Values are presented by weight percentage of the hydrogel polymer composition.Table 1

[0099] While in its broadest embodiments, any biocompatible surgical mesh matrix may be utilized in the biocompatible hydrogel coated surgical meshes described herein, in some embodiments, suitable matrices are as described below.

[0100] Surgical meshes are versatile materials available in various forms, including flexible sheets, and are fabricated from both synthetic and natural materials. These meshes can be categorized based on filament structure, pore size, and weight. Filament structures include monofilament, multifilament, or multifilament fibers derived from monofilament materials. Mesh pore sizes typically range from approximately 200 pm to 5000 pm. Smaller pore sizes (e.g., 1000 pm or less) are commonly associated with heavyweight meshes, while larger pore sizes (e.g., greater than 1000 pm) are characteristic of lightweight meshes. Mesh weight is generally expressed in grams per square meter (g / m2), with heavyweight meshes having densities of 80-100 g / m2and lightweight meshes ranging from 25-45 g / m2. Suitable surgical meshes include those produced through weaving, knitting, molding, or unitary and multi-component fabrication processes, as well as other manufacturing methods.

[0101] In certain embodiments, the mesh matrix comprising the hydrogel coated biocompatible surgical meshes described herein may be composed of a non-biodegradable material (also referred to as non-absorbable or non-resorbable), a biodegradable material (also referred to as absorbable or resorbable), or composite material i.e., a combination of both non-biodegradable and biodegradable material. As used herein, “biodegradable material” refers to any material capable of being degraded within the body of a mammalian recipient through endogenous hydrolytic, enzymatic, or cellular processes. Depending on the specific composition of the material, its degradation products may be metabolized and recycled via normal metabolic pathways or eliminated through one or more organ systems. In contrast, a “non-biodegradable material” is defined as a material that cannot be degraded within the body of a mammalian recipient by endogenous hydrolytic, enzymatic, or cellular processes.

[0102] Polymers used to make non-biodegradable surgical mesh matrices include polypropylene, polyester, i.e., polyethylene terephthalate, polytetrafluoroethylene (PTFE), or polyvinylidene fluoride. Examples of commercially available polypropylene mesh matrices include but are not limited to: Marlex™ (CR Bard, Inc., Cranston R.I.), Visilex® (CR Bard, Inc., Cranston R.I.), PerFix® Plug (CR Bard, Inc., Cranston R.I.), Kugel™ Hernia Patch (CR Bard, Inc., Cranston R.I.), 3DMax (CR Bard, Inc., Cranston R.I.), Prolene™ (Ethicon, Inc., Somerville, N.J.), Surgipro™ (Autosuture, U.S. Surgical, Norwalk, Conn.), Prolite™ (Atrium Medical Co., Hudson, N.H.), Prolite Ultra™ (Atrium Medical Co., Hudson, N.H.), Trelex™(Meadox Medical, Oakland, N.J.), ProGrip™ (Medtronic), and Parietene® (Medtronic).Examples of commercially available polyester mesh matrices include but are not limited to: Mersilene™ (Ethicon, Inc., Somerville, N.J.) and Parietex® (Medtronic), and DynaMesh® (FEG Textiltechnik, Germany). Examples of commercially available Expanded PTFE (ePTFE) mesh matrices include, but are not limited to: Gore-Tex® Soft Tissue Patch (W. L. Gore & Associates, Newark, Del.), Dualmesh® (W. L. Gore & Associates, Newark, Del.), Dualmesh® Plus (W. L. Gore & Associates, Newark, Del.), Dulex® (OR Bard, Inc., Cranston R.I.), and Reconix® (CR Bard, Inc., Cranston R.I.). Examples of commercially available polyvinylidene fluoride (PVDF) mesh matrices include but are not limited to: DynaMesh® PVDF (FEG, Textiltechnik). Examples of nylon (polyamide) mesh matrices include but are not limited to: Dermalene® (Ethicon, Inc., Somerville, N.J.), Bard Polyamide Mesh (CR Bard, Inc., Cranston R.I.), and Sofradim Production (Medtronic). In certain embodiments, the hydrogel coated surgical meshes described herein comprise a polypropylene mesh matrix. In certain embodiments, the surgical mesh is Prolene™.

[0103] Biodegradable surgical mesh matrices which include biologic biodegradable meshes are also available from commercial sources. Polymers used to make biodegradable mesh matrices include but are not limited to polyglycolic acid, polyglactin 910, polylactic acid, poly-4-hydroxybutyrate, polycaprolactone and trimethylene carbonate. Examples of commercially available polyglycolic mesh matrices include but are not limited to Dexon™ (Medtronic). Examples of commercially available polyglactin 910 mesh matrices include but are not limited to Vicryl™ (Ethicon, Inc., Sommerville, N.J.). Examples of commercially available polylactic acid (PLA) mesh matrices include but are not limited to TIGR® MATRIX (copolymer) (Novus Scientific, Uppsala, Sweden). Examples of commercially available polydioxane (PDO) mesh matrices include but are not limited to TIGR® Matrix (Novus Scientific, Uppsala, Sweden). Examples of commercially available poly-4-hydroxybutyrate (P4HB) mesh matrices include but are not limited to Phasix™ Mesh (Beckton Dickinson). Examples of commercially available polycaprolactone (PCL) mesh matrices include but are not limited to TissueMate® (Gunze Limited, Japan), and Osteomesh® (Osteopore International, Singapore). Examples of trimethylene carbonate (TMC) mesh matrices include but are not limited to TIGR® Matrix Surgical Mesh (Novus Scientific, Uppsala, Sweden), Biodegradable TMC-PLA Blends (BMG Incorporated, Evansville, Indiana, USA), and Customized TMC-PLA Blends (Corbion, Netherlands). Biologic biodegradable meshes which are derived from natural tissues, such as porcine or bovine sources, and are decellularized to remove antigens. Examples of commercially available biologic biodegradable mesh matrices include but are not limited to Strattice ™ (Allergan), OviTex® (Tela Bio), Permacol™ (Medtronic), Veritas® Collagen Matrix (Baxter), XenMatrix™ (BD Bard),AlloDerm® (LifeCell), and FlexHD® (MTF Biologies). In certain embodiments, the hydrogel coated surgical meshes described herein comprise a poly-4-hydroxybutyrate (P4HB) mesh matrix. In certain embodiments, the surgical mesh is Phasix™ Mesh.

[0104] Composite meshes, i.e., meshes that include both biodegradable and non-biodegradable materials can be made either from combinations of the materials described above or from additional materials. Examples of composite meshes include but are not limited to polypropylene / PTFE, polypropylene / cellulose, polypropylene / Vicryl, polypropylene / Seprafilm®, polypropylene / Monocryl(poliglecaprone), and polyester / collagen. Examples of commercially available polypropylene / PTFE mesh matrices include but are not limited to: Composix® (CR Bard, Inc., Cranston R.I.), Composix® E / X (CR Bard, Inc., Cranston R.I.), and Ventralex® (CR Bard, Inc., Cranston R.I.). Examples of commercially available polypropylene / cellulose mesh matrices include but are not limited to: Proceed™ (Ethicon, Inc., Somerville, N.J.), polypropylene / Seprafilm®: Sepramesh® (Genzyme, Cambridge, Mass.), Sepramesh® IP (Genzyme, Cambridge, Mass.). Examples of commercially available polypropylene / Vicryl mesh matrices include but are not limited to: Vypro™ (Ethicon, Somerville, N.J.), Vypro™ II (Ethicon, Somerville, N.J.). Examples of commercially available polypropylene / Monocryl(poliglecaprone) mesh matrices include but are not limited to: Ultrapro® (Ethicon, Somerville, N.J.). Examples of commercially available polyester / collagen mesh matrices include but are not limited to: Parietex® Composite (Medtronic).

[0105] In certain embodiments, the biocompatible hydrogel coated surgical mesh compositions described herein may be used for surgical applications where biodegradable and non-biodegradable surgical mesh compositions are currently being used for treating, for example, complications associated with hernia repair surgery, prevention of infection, and / or enhance recovery from repair of the hernia.

[0106] In certain embodiments, the biocompatible hydrogel coated surgical mesh compositions described herein, when comprising an antimicrobial agent alone or in combination with other non-antimicrobial therapeutic agents, are suitable for treating or reducing infections, and / or enhancing hernia surgery recovery across a wide range of conditions requiring hernia repair or reconstruction. These conditions may include congenital malformations, traumatic injuries, infections, and oncologic resections. Accordingly, the hydrogel-coated surgical mesh compositions may incorporate any suitable therapeutically effective therapeutic component to treat or prevent infection, and / or facilitate the repair ofdefects in soft tissues, such as those that connect, support, or surround other structures and organs of the body. Examples of hernias that may be treated using the biocompatible hydrogel coated surgical meshes described herein include but are not limited to: direct inguinal hernias, indirect inguinal hernias, femoral hernias, scrotal hernias, Spigelian hernia, obturator hernia, Petit's hernia, Grynfeltt's hernia, Richter's hernia, Hesselbach's hernia, pantaloon hernia, Cooper's hernia, epigastric hernia, diaphragmatic or hiatal hernias, e.g., Bochdalek's hernia and Morgagni's hernia, and umbilical hernia.

[0107] In certain embodiments, the biocompatible hydrogel coated surgical meshes described herein may also be used in breast reconstruction applications and in bone repair applications, serving as a periosteal graft to support bone regeneration or as an articular graft to promote cartilage repair.

[0108] In certain embodiments, the biocompatible hydrogel coated surgical meshes described herein may be used to address complications or facilitate procedures associated with multidisciplinary management of cancer patients in addition to treating or preventing microbial infection including bacterial infection, and / or inflammation. For example, in certain embodiments, the biocompatible hydrogel coated surgical meshes described herein may be used for reconstruction following tumor resection, particularly for cancers affecting the abdominal wall, chest wall, or pelvic region. In certain embodiments, the biocompatible hydrogel coated surgical meshes described herein may be used for hernia repair in cancer patients, especially those who have undergone surgery, radiation therapy, or have abdominal metastases, who are at higher risk of hernias. In certain embodiments, the biocompatible hydrogel coated surgical meshes described herein may be used after cancer related surgeries like pelvic exenteration for gynecological cancers to reconstruct or support pelvic structures.

[0109] Certain embodiments provide for a method for treating a hernia in a subject in need thereof, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component. In certain such embodiments, the biocompatible surgical mesh matrix may comprise of any one of the polymers described herein. In certain such embodiments, the biocompatible surgical mesh matrix may comprise any one of thecommercially available surgical meshes described herein. In certain such embodiments, the hydrogel polymer matrix may comprise any one of the anionic gelling polymers and inverse thermal gelling polymers described herein. In certain such embodiments, the anionic gelling polymer is hyaluronan. In certain such embodiments, the inverse thermal gelling polymer is methylcellulose. In certain such embodiments, the therapeutic component may comprise any one of the therapeutic agents described herein. In certain such embodiments, the therapeutic component may comprise an antimicrobial agent for the treatment of surgical site infections. In certain such embodiments, the antimicrobial agent may comprise an antibiotic. In certain other such embodiments, the therapeutic component may be a combination of an antimicrobial agent and a non-antimicrobial agent. In certain other such embodiments, the antimicrobial agent may be an antibiotic, and the non-antimicrobial agent may be an antiinflammatory agent, an angiogenesis promoter or a combination thereof.

[0110] Certain embodiments provide for a method for treating surgical site infections in a subject in need thereof, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent. Certain other embodiments provide for a method of prophylactically preventing a surgical site infection in a patient in need thereof.

[0111] Certain embodiments provide fora method for treating, including prophylactically treating, surgical site infections in a subject treated for hernia, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer matrix, (b) positioning the surgical mesh at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia wherein hydrogel polymer matrix comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent. In certain such embodiments, the biocompatible surgical mesh matrix may comprise of any one of the polymers described herein. In certain such embodiments, the biocompatible surgical mesh matrix may comprise of any one of the commercially available surgical meshes described herein. In certain such embodiments, the anionic gelling polymer comprising the hydrogel polymer matrix may comprise any one of the anionic gelling polymers and inverse thermal gelling polymers described herein. In certain such embodiments, the anionic gelling polymeris hyaluronan. In certain such embodiments, the inverse thermal gelling polymer is methylcellulose. In certain such embodiments, the antimicrobial agent may comprise an antibiotic agent. In certain other such embodiments, the therapeutic component may comprise a combination of an antimicrobial agent and a non-antimicrobial agent. In certain such embodiments, the therapeutic components may comprise an antibiotic and a nonantibiotic agent. In certain other such embodiments, the therapeutic components may comprise an antibiotic agent and an agent selected from an anti-inflammatory agent, an angiogenesis promoter, or a combination thereof.

[0112] Embodiments comprising kits or pharmaceutical packages are contemplated herein.

[0113] For example, certain embodiments contemplate a surgical hernia mesh kit comprising: (a) a surgical mesh comprising a biocompatible mesh matrix coated with a hydrogel polymer composition, b) a sealed container housing the surgical mesh to maintain sterility, c) one or more surgical instruments for positioning and securing the mesh at the site of the hernia, and, optionally, d) instructions for use, detailing one or more of sterile handling of the surgical mesh and the placement and fixation of the surgical mesh in a subject in need thereof, wherein the hydrogel polymer composition comprises: (i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component. In certain kit embodiments, the biocompatible surgical mesh matrix may comprise any one of the mesh matrix polymers described herein. In certain kit embodiments, the biocompatible surgical mesh matrix comprises a biodegradable matrix, such as for example, a poly-4-hydroxybutyrate mesh matrix (e.g., Phasix™ Mesh). In certain kit embodiments, the biocompatible surgical mesh matrix comprises a non-biodegradable matrix, such as for example, a polypropylene mesh matrix (e.g., Prolene™). In certain kit embodiments, the anionic gelling polymer and the inverse thermal gelling polymer may comprise any one of the anionic gelling polymers and inverse thermal gelling polymers identified herein. In certain kit embodiments, the anionic gelling polymer comprises hyaluronan and the inverse thermal gelling polymer comprises methylcellulose. The therapeutic component may be selected from any one of the therapeutic agents described herein depending on the nature of the surgery, hernia repair or reconstructive surgery. In certain embodiments, the therapeutic component comprises an antimicrobial agent optionally in combination with a non-antimicrobial agent, such as for example an antiinflammatory agent and / or an angiogenesis promoter. In certain embodiments the antimicrobial agent comprises an antibiotic agent. The kit may comprise a surgical toolappropriate for positioning and securing the surgical mesh for the particular hernia or reconstructive surgery. Such surgical tools are well known in the art. The kits contemplated herein may also include directions on how the hydrogel coated biocompatible surgical meshes should be handled to preserve the structural integrity of the hydrogel polymer composition coating the surgical mesh matrix.

[0114] Suitably, the hydrogel coated surgical meshes described herein are manufactured as precoated products to ensure consistent application of the hydrogel polymer composition, simplify surgical procedures, and provide ready-to-use implants with optimized therapeutic component distribution and controlled release properties. However, due to the shear thinning nature of the hydrogel polymer composition, the hydrogel polymer composition may be provided, in certain embodiments, as a customizable solution, allowing surgeons to apply the hydrogel polymer composition directly onto the surgical mesh matrix immediately before implantation during surgery. This approach enables tailored application of the hydrogel polymer composition to meet specific surgical needs, therapeutic requirements, or patient conditions, while leveraging its shear-thinning properties for easy handling and uniform coating.

[0115] Thus, certain embodiments provide for a kit comprising: (a) an uncoated surgical mesh comprising a biocompatible mesh matrix, (b) a sealed container housing the surgical mesh to maintain sterility, (c) a prefilled syringe comprising a hydrogel polymer composition, (d) optionally one or more surgical instruments for positioning and securing the mesh at the site of the hernia, and, optionally, (e) instructions for use, detailing one or more of the application of the hydrogel polymer composition onto the uncoated surgical mesh matrix, sterile handling of the surgical mesh, and placement and fixation of the coated surgical mesh in a subject in need thereof, wherein the hydrogel polymer composition comprises: (i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component. In certain kit embodiments, the biocompatible surgical mesh matrix may comprise any one of the mesh matrix polymers described herein. In certain kit embodiments, the biocompatible surgical mesh matrix comprises a biodegradable matrix, such as for example, a poly-4-hydroxybutyrate mesh matrix (e.g., Phasix™ Mesh). In certain kit embodiments, the biocompatible surgical mesh matrix comprises a non-biodegradable matrix, such as for example, a polypropylene mesh matrix (e.g., Prolene™). In certain kit embodiments, the anionic gelling polymer and the inverse thermal gelling polymer may comprise any one of the anionic gelling polymers and inverse thermal gelling polymers described herein. In certain kit embodiments, the anionic gellingpolymer comprises hyaluronan and the inverse thermal gelling polymer comprises methylcellulose. The therapeutic component may comprise any one of the therapeutic agents described herein depending on the nature of the hernia repair or reconstructive surgery. In certain embodiments, the therapeutic component comprises an antimicrobial agent optionally in combination with a non-antimicrobial agent, such as for example an antiinflammatory agent and / or an angiogenesis promoter. In certain embodiments the antimicrobial agent comprises an antibiotic agent. The kit may comprise a surgical tool appropriate for positioning and securing the surgical mesh for the particular hernia or reconstructive surgery. Such surgical tools are well known in the art. The kits contemplated herein may also include directions on how the hydrogel coated biocompatible surgical meshes should be handled to preserve the structural integrity of the hydrogel polymer composition after coating the surgical mesh matrix.

[0116] Certain embodiments contemplate a pharmaceutical package comprising a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of a therapeutic component, b) a sealed container housing the surgical mesh to maintain sterility, and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of hernias, and the therapeutic benefits provided by the hydrogel polymer coating. In certain pharmaceutical package embodiments, the biocompatible surgical mesh matrix may comprise any one of the polymers described herein. In certain pharmaceutical package embodiments, the biocompatible surgical mesh matrix comprises a biodegradable matrix, such as for example, a poly-4-hydroxybutyrate mesh matrix (e.g., Phasix™ Mesh). In certain pharmaceutical package embodiments, the biocompatible surgical mesh matrix comprises a non-biodegradable matrix, such as for example, a polypropylene mesh matrix (e.g., Prolene™). In certain pharmaceutical package embodiments, the anionic gelling polymer and the inverse thermal gelling polymer may comprise any one of the anionic gelling polymers and inverse thermal gelling polymers described herein. In certain pharmaceutical package embodiments, the anionic gelling polymer comprises hyaluronan and the inverse thermal gelling polymer comprises methylcellulose. The therapeutic component may comprise any one of the therapeutic agents described herein depending on the nature of the hernia repair or reconstructive surgery. In certain pharmaceutical package embodiments, the therapeutic component comprises an antimicrobial agent optionally in combination with a non-antimicrobial agent, such as for example an anti-inflammatory agent and / or an angiogenesis promoter. In certain embodiments the antimicrobial agent comprises an antibiotic agent. The pharmaceutical package contemplated herein may also include directions on how the hydrogel coatedbiocompatible surgical meshes should be handled to preserve the structural integrity of the hydrogel polymer composition coating the surgical mesh matrix.

[0117] The biocompatible hydrogel coated surgical meshes described herein may be applied to a subject in need of treatment using techniques well known in the art. These compositions can be utilized in various ways, including: (a) wrapping them around damaged tissue or a tissue containing a defect; (b) placing them directly on the surface of damaged tissue or tissue with a defect; or (c) rolling them up and inserting them into a cavity, gap, or space within the tissue.

[0118] All documents which may be referenced herein are incorporated by reference, however, it should be appreciated that any patent, publication, or other disclosure material, in whole or in part, that is incorporated by reference herein is incorporated only to the extent that the incorporated material does not conflict with definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference.

[0119] It will be understood that numerous modifications thereto will appear to those skilled in the art. Accordingly, the above description and accompanying drawings should be taken as illustrative of the invention and not in a limiting sense. It will further be understood that it is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features herein before set forth, and as follows in the scope of the appended claims.

[0120] The embodiments of the invention described above are intended to be exemplary only. The scope of the invention is therefore intended to be limited solely by the scope of the appended claims.EXAMPLESExample 1

[0121] Surgical meshes were cut into squares and weighed before coating. HAMC was loaded into a 500 uL glass syringe equipped with 16G needle. To each mesh square was added 50 uL gel per cm2mesh. The gel was then spread out evenly using a scalpel. The gels were incubated at 4 °C for 4 hours, then cured at 37 °C for at least 20 hours. The dry, coated meshes were used either immediately or stored at 4 °C until use.

[0122] The dry, coated meshes were reweighed before use to calculate drug loading. For bending experiments, the meshes were bent three times along two different axes, then the meshes were weighed again. Drug loading was calculated as:Drug loading = (mc- muc) * pdwhere mcisthe mass of the dry, coated mesh, mucis the mass of the uncoated mesh, and pdis the theoretical proportion of drug in the dry solid, as determined by the total mass of polymers and drugs added to the initial formulation.Example 2

[0123] Phasix™ mesh was cut into 2x2 cm2squares and coated with compositions 1-4 (Table 1) using the procedure described in Example 1.

[0124] To perform bending tests, the meshes were bent at least 90 degrees using forceps 3 times along each diagonal axis and weighed before and after bending. Drug loading for each Composition was calculated as described in Example 1. Results of this test for Compositions 1-4 is shown in Figure 1.Example 3

[0125] Phasix™ mesh was cut into 1.5x1.5 cm2squares and coated with Compositions 1-4 (Table 1) using the procedure described in Example 1.

[0126] Release rates were initiated by immersing meshes in 100 mL of 0.5% sodium dodecyl sulfate (SDS) in phosphate buffered saline (PBS). The releases were maintained at 37 °C on a 60 rpm shaker. At designated timepoints, 1.000 mL of the release medium was sampled and replaced with 1.000 mL fresh 0.5% SDS in PBS. Antibiotic content was determined by reverse phase HPLC. A Waters C18column was used as the stationary phase. For cefazolin, the mobile phases used were 12.5 mM phosphate (pH 8.0) (A) andacetonitrile (B). A linear gradient of 10-70% B from 0-7 minutes followed an isocratic equilibration of 10% B from 7.01 to 10 minutes was performed for each run. Cefazolin was detected by absorbance at 272 nm. For vancomycin, the mobile phase used was 90:10 0.1% formic acid:acetonitrile. Each run lasted 6 minutes and vancomycin was detected by absorbance at 280 nm. For erythromycin, the mobile phase used was 50:50 12.5 mM phosphate (pH 8.0):acetonitrile. Each run lasted 13 minutes and erythromycin was detected by absorbance at 205 nm. For tetracycline, the mobile phase used was 85:150.1% formic acid:acetonitrile. Each run lasted 8 minutes and tetracycline was detected by absorbance at 357 nm. Result of these embodiments for Compositions 1-4 is shown in Figure 2.Example 4

[0127] One plate of tryptic soy agar was streaked with Staphylococcus aureus from a frozen stock (kept at -70°C), and incubated overnight (16-18h) at 37°C. Using a sterile inoculation loop, one single colony of S. aureus was selected from the streaked plate and used to inoculate 4 mL tryptic soy broth in a 13 mL round-bottom test tube. The inoculated tube was incubated at 37°C with agitation at 200 rpm overnight (16-18h).

[0128] After 16-18h of incubation, 200uL of the overnight culture in broth were used to inoculate 20ml_ of sterile broth in an Erlenmeyer flask. The culture flask was incubated at 37 °C with agitation at 200 rpm. The optical density (OD) at 600nm was recorded for the sterile broth (Blank) and the S. aureus culture at t=0, and for the culture only every 30-60 minutes.

[0129] When the OD value of the bacteria culture reached ~0.8 (equivalent to 4-8x107colony forming units, based on an already established growth curve of S. aureus), 100uL of the culture were dispensed on an agar plate and evenly distributed using a sterile cell spreader.

[0130] The following conditions were evaluated right after S. aureus was seeded on agar plates, as previously described:A. Hernia mesh coated with Composition 1 at pH 7.4 (~4mg / cm2)B. Uncoated hernia meshC. Hernia mesh coated with HAMC at pH 7.4

[0131] A piece of 1x1cm of coated and uncoated mesh was placed in the center of the inoculated agar plate, and 40uL of sterile PBS were carefully placed on top of the mesh to help keep it in place.

[0132] Plates were incubated at 37°C for at least 20h, and pictures were taken to record the bacteria growth. Results are shown in Figure 3 which shows a clear zone of inhibition around the mesh of plate A.

[0133] Further embodiments include the subject matter of the following clauses.1. A hydrogel coated surgical mesh comprising: (1) a biocompatible mesh matrix, and (2) a hydrogel polymer composition; said hydrogel polymer composition comprising (a) an anionic gelling polymer, (b) an inverse thermal gelling polymer, and (c) a therapeutically effective amount of a therapeutic component; wherein said mesh matrix is coated with said hydrogel polymer composition.2. The hydrogel coated surgical mesh of clause 1 wherein the surgical mesh matrix comprises a synthetic polymer.3. The hydrogel coated surgical mesh of clause 2 wherein the synthetic polymer comprises at least one non-biodegradable polymer.4. The hydrogel coated surgical mesh of clause 3 wherein the non-biodegradable polymer is selected from the group consisting of polypropylene, expanded polytetrafluoroethylene, polyester, polyvinylidene fluoride, nylon, and any combination thereof.5. The hydrogel coated surgical mesh of clause 4 wherein the non-biodegradable polymer is polypropylene.6. The hydrogel coated surgical mesh of clause 2 wherein the synthetic polymer comprises at least one biodegradable polymer.7. The hydrogel coated surgical mesh of clause 6 wherein the biodegradable polymer is selected from the group consisting of polyglycolic acid, polylactic acid, polydioxanone, poly-4-hydroybutyrate, polyglycolide-co-lactide, polycaprolactone, and trimethylene carbonate.8. The hydrogel coated surgical mesh of clause 7 wherein the biodegradable polymer is poly-4-hydrobutyrate.9. The hydrogel coated surgical mesh of any one of clauses 1-8 wherein the surgical mesh matrix comprises at least one natural polymer.10. The hydrogel coated surgical mesh of clause 9 wherein the natural polymer is selected from the group consisting of collagen, silk fibroin, chitosan, and decellularized extra cellular matrix.11. The hydrogel coated surgical mesh of any one of clauses 1-10 wherein the anionic polymer is selected from the group consisting of hyaluronan (HA), derivatives of hyaluronan, alginate, derivatives of alginate, carboxymethyl cellulose (CMC), carboxyethyl cellulose (CEC), derivatives of hydroxypropyl cellulose (HPC), derivatives of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl methyl cellulose phthalate (HPMCP), sodium carboxymethyl cellulose (Na-CMC), phosphorylated cellulose, sulfated cellulose, acrylates, C10-30 alkyl acrylate crosspolymer, carbomer, polyacrylic acid (PAA), poly(methacryclic acid) and mixtures thereof.12. The hydrogel coated surgical mesh of any one of clauses 1-11 wherein the anionic polymer is hyaluronan.13. The hydrogel coated surgical mesh of any one of clauses 1-12 wherein the inverse thermal gelling polymer is selected from the group consisting of methylcellulose, a chitosan and p-glycerophosphate solution, collagen, tri-block copolymer of polyethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol), tri-block copolymer of polypropylene glycol)-poly(ethylene glycol)-poly (propylene glycol), poly(N-isopropyl acrylamide), agarose, copolymers of poly-N-isopropylacrylamide, polysaccharides and mixtures thereof.14. The hydrogel coated surgical mesh of any one of clauses 1-13 wherein the inverse thermal gelling polymer is methylcellulose.15. The hydrogel coated surgical mesh of clause 12 wherein the hyaluronan is present from 0.5-3% (wt / wt) of the hydrogel polymer matrix.16. The hydrogel coated surgical mesh of clause 14 wherein the methylcellulose is present from 0.5-8% (wt / wt) of the hydrogel polymer matrix.17. The hydrogel coated surgical mesh of any one of clauses 1-16 wherein the anionic polymer is hyaluronan and the inverse thermal gelling polymer is methylcellulose and the ratio of hyaluronammethylcellulose in the hydrogel polymer matrix is from 1:1 - 1:7 (wt / wt).18. The hydrogel coated surgical mesh of clause 17 wherein the ratio of hyaluronammethylcellulose is 1:1 (wt / wt).19. The hydrogel coated surgical mesh of clause 17 wherein the ratio of hyaluronammethylcellulose is 1.4:2 (wt / wt).20. The hydrogel coated surgical mesh of clause 17 wherein the ratio of hyaluronammethylcellulose is 2:7 (wt / wt).21. The hydrogel coated surgical mesh of any one of clauses 1-20 wherein the therapeutic component is selected from the group consisting of an anti-inflammatory agent, an angiogenesis promoter, an antimicrobial agent, and any combination thereof.22. The hydrogel coated surgical mesh of any one of clauses 1-20 wherein the therapeutic component comprises a combination of an antibiotic agent and a non-antibiotic antimicrobial agent.23. The hydrogel coated surgical mesh of clause 21 wherein the anti-inflammatory agent is selected from the group consisting of dexamethasone, prednisolone, triamcinolone acetonide, ketorolac, ibuprofen, celecoxib, tacrolimus, pirfenidone, lnterleukin-1, curcumin, resveratrol, and any combination thereof.24. The hydrogel coated surgical mesh of clause 21 wherein the antimicrobial agent is selected from the group consisting of antibiotics, antifungal compounds, non-antibiotic antiseptics, broad spectrum antimicrobial, antimicrobial peptides, and any combination thereof.25. The hydrogel coated surgical mesh of clause 24 wherein the antibiotic is selected from the group consisting of p-lactams, glycopeptides, lipoglycopeptides, macrolides, tetracyclines, aminoglycosides, fluroquinolones, folate pathway inhibitors, oxazolidinones, lincosamides, rifamycins, nitroimidazoles, polypeptide antibiotics, and any combination thereof.26. The hydrogel coated surgical mesh of clause 24 wherein the antibiotic agent is selected from the group consisting of gentamicin, vancomycin, ciprofloxacin, amoxicillin- clavulanic acid, cefazolin, amikacin, colisitin, rifampin, minocycline, metronidazole, tobramycin, erythromycin, tetracycline, their respective pharmaceutically acceptable salts, and any combination thereof.27. The hydrogel coated surgical mesh of clause 21 wherein the angiogenesis promoter is selected from the group consisting of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDFGF), angiopoietin Ang-1, angiopoietin Ang-2, lnterleukin-8 (IL-8) , granulocyte-macrophage colonystimulating factor (GM-CSF), collagen, heparin, thalidomide derivatives, prostaglandin E1 (PGE1), dimethyloxalyglycine (DMOG), exosomes from mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), angiomodulin, erythropoietin, and any combination thereof.28. The hydrogel coated surgical mesh of clause 24 wherein the antibiotic agent is present in both its acidic and basic form.29. The hydrogel coated surgical mesh of clause 28 wherein the acidic form of the antibiotic agent provides for an immediate release of the antibiotic agent and the basic form provides for a controlled release of the antibiotic agent for at least one week at body temperature.30. A method for treating hernia repair surgery in a patient, comprising:(a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component.31. The method of clause 30 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-29.32. A method of treating a surgical site infection in a patient, comprising:(a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.33. The method of clause 32 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-29.34. A method of treating a surgical site infection in a patient treated for hernia repair surgery, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.35. The method of clause 34, wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-29.36. A method of prophylactically preventing a surgical site infection in a patient, comprising:(a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.37. The method of clause 36, wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-2938. A method of prophylactically preventing a surgical site infection in a patient treated for hernia repair surgery, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue toreinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.39. The method of clause 38 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-2940. Use of the hydrogel coated surgical mesh of any one of clauses 1-29 for the treatment of hernia in a patient in need thereof.41. Use of the hydrogel coated surgical mesh of any one of clauses 1-29 for the treatment of surgical site infection in a patient in need thereof.42. Use of the hydrogel coated surgical mesh of any one of clauses 1-29 for the treatment of surgical site infection in a patient treated for hernia repair surgery.43. Use of the hydrogel coated surgical mesh of any one of clauses 1-29 for prophylactically preventing surgical site infection in a patient in need thereof.44. A surgical hernia mesh kit comprising:(a) a surgical mesh comprising a biocompatible material coated with a hydrogel polymer composition, b) one or more surgical instruments for positioning and securing the mesh at the site of the hernia, and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh and the placement and fixation of the surgical mesh in a subject in need thereof, wherein the hydrogel polymer composition comprises: (i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of a therapeutic component.45. The kit of clause 44 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-29.46. Use of the kit of any one of clauses 44-45 for the treatment of hernia repair surgery in a patient in need thereof.47. Use of the kit of any one of clauses 44-45 for the treatment of surgical site infection in a patient in need thereof.Use of the kit of any one of clauses 44-45 for the treatment of surgical site infection in a patient treated for hernia repair surgery.Use of the kit of any one of clauses 44-45 for prophylactically preventing a surgical site infection in a patient treated for hernia repair surgery.Use of the kit of any one of clauses 44-45 for prophylactically preventing a surgical site infection in a patient in need thereof.A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of a therapeutic component, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of hernia repair surgery and the therapeutic benefits provided by the hydrogel polymer coating.A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of at least one antimicrobial agent, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of surgical site infection or for prophylactically preventing surgical site infections and the therapeutic benefits provided by the hydrogel polymer coating.A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of at least one antimicrobial agent, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of surgical site infection or for prophylactically preventing surgical site infections for a patient treated for hernia repair surgery and the therapeutic benefits provided by the hydrogel polymer coating.54. The pharmaceutical package of any one of clauses 51-53 wherein the surgical mesh comprises the synthetic polymer of any one of clauses 3-8.55. The pharmaceutical package of any one of clauses 51-53 wherein the surgical mesh comprises the natural polymer of clause 10.56. The pharmaceutical package of clauses 51-53 wherein the hydrogel polymer composition comprises the anionic gelling polymer and the inverse thermal gelling polymer of any one of clauses 11-20.57. The pharmaceutical package of clause 51 wherein the therapeutic component comprises any one of the therapeutic components of clauses 21-29.58. The pharmaceutical package of any one of clauses 52-53 wherein the antimicrobial agent comprises the antibiotic agent of clause 25.59. The pharmaceutical package of clause 51 wherein the therapeutic component comprises an antibiotic agent of clause 25 in combination with an anti-inflammatory agent of clause 23.60. The pharmaceutical package of clause 51 wherein the therapeutic component comprises an antibiotic agent of clause 25 in combination with an angiogenesis promoter of clause 27.61. The pharmaceutical package of clause 51 wherein the therapeutic component comprises an antibiotic agent in combination with an anti-inflammatory agent of clause 23 and an angiogenesis promoter of clause 27.62. The pharmaceutical package of clause 52-53 wherein the hydrogel polymer composition further comprises an anti-inflammatory agent of clause 23.63. The pharmaceutical package of clause 52-53 wherein the hydrogel polymer composition further comprises an angiogenesis promoter of clause 27.64. The pharmaceutical package of clause 52-53 wherein the hydrogel polymer composition further comprises an anti-inflammatory agent of clause 23 in combination with an angiogenesis promoter of clause 27.65. The pharmaceutical package of clause 52-53 wherein the antibiotic is selected from the group consisting of cefazolin, vancomycin, erythromycin, tetracycline, and any combination thereof.66. A method of manufacturing a surgical mesh comprising: (a) providing a biocompatible matrix; (b) coating the biocompatible matrix with a hydrogel polymer composition comprising: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antibiotic agent; and (c) drying the hydrogel polymer coating.67. The method of clause 66 further comprising drying the hydrogel polymer coating for at least 20 hours, optionally at a temperature of between about 30°C and about 45°C.68. The method of clause 67, further comprising incubating the hydrogel polymer coating at a temperature of between 1 °C and 4°C for a period of 2 and 6 hours prior to drying.69. The method of any one of clauses 66-68 further comprising physically blending the anionic gelling polymer and the inverse thermal gelling polymer and dispersing the at least one antibiotic agent therein.70. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or 100% of the therapeutic component is released within 24 hours of application at the site of surgery at physiological temperature.71. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein no more than 60%, no more than 50%, no more than 40%, no more than 30%, or no more than 20% of the therapeutic component is released within 1 hour of application.72. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein no more than 95%, no more than 90%, or no more than 80% of the therapeutic component is released within 3 hours of application.73. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the therapeutic component is released within 6 hours of application.74. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein the hydrogel polymer composition provides an early bolus release of therapeutic component within 1 hour to reduce bacterial burden.75. The hydrogel coated surgical mesh of clause 74, wherein the bolus release comprises at least 20%, at least 30%, or at least 40% of the total therapeutic component.76. The hydrogel coated surgical mesh of any one of clauses 70-75, wherein the therapeutic component comprises an antimicrobial agent.77. The hydrogel coated surgical mesh of any one of clauses 70-76 wherein the therapeutic component comprises an antibiotic agent.78. The method of any one of clauses 29-38, wherein at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or 100% of the therapeutic component is released from the hydrogel polymer composition within 24 hours of application at the site of surgery at physiological temperature.79. The method of any one of clauses 29-38, wherein no more than 60%, no more than 50%, no more than 40%, no more than 30%, or no more than 20% of the therapeutic component is released within 1 hour of application.80. The method of any one of clauses 29-38, wherein no more than 95%, no more than 90%, or no more than 80% of the therapeutic component is released within 3 hours of application.81. The method of any one of clauses 29-38, wherein at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the therapeutic component is released within 6 hours of application.82. The method of any one of clauses 29-38, wherein the hydrogel polymer composition provides an early bolus release of therapeutic component within 1 hour to reduce bacterial burden.83. The method of clause 82, wherein the bolus release comprises at least 20%, at least 30%, or at least 40% of the total therapeutic component.84. The method of any one of clauses 78-83, wherein the therapeutic component comprises an antimicrobial agent.85. The method of any one clauses 78-83, wherein the therapeutic component comprises an antibiotic agent.86. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein the therapeutic component is present at 1-20% (wt / wt), 2-18% (wt / wt), 3-15% (wt / wt), 5-15% (wt / wt), or 6-8% (wt / wt) of the hydrogel polymer composition.87. The hydrogel coated surgical mesh of clause 86, wherein the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition.88. The hydrogel coated surgical mesh of any one of clauses 86-87, wherein the therapeutic component comprises an antimicrobial agent.89. The hydrogel coated surgical mesh of any one of clauses 86-87, wherein the therapeutic component comprises an antibiotic agent.90. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein the therapeutic component comprises a combination of an antibiotic agent, an anti-inflammatory agent, and / or an angiogenesis promoter, and wherein the combined therapeutic component loading is 3-30% (wt / wt) of the hydrogel polymer composition, with each therapeutic agent independently present at 1-15% (wt / wt).91. The method of any one of clauses 29-38, wherein the hydrogel polymer composition comprises a therapeutic component present at 1-20% (wt / wt), 2-18% (wt / wt), 3-15% (wt / wt), 5-15% (wt / wt) or 6-8% (wt / wt) of the hydrogel polymer composition.92. The method of clause 91 , wherein the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition.93. The method of any one of clauses 91-92, wherein the therapeutic component comprises an antimicrobial agent.94. The method of any one of clauses 91-92, wherein the therapeutic component comprises an antibiotic agent.95. The method of any one of clauses 29-38, wherein the therapeutic component comprises a combination of an antibiotic agent, an anti-inflammatory agent, and / or an angiogenesis promoter, and wherein the combined therapeutic component loading is 3-30% (wt / wt) of the hydrogel polymer composition, with each therapeutic agent independently present at 1-15% (wt / wt).96. The hydrogel coated surgical mesh of any one of clauses 1-28, wherein bending of the mesh results in no more than 20%, 15%, 10%, 5%, or 2% loss of therapeutic component.97. The hydrogel coated surgical mesh of clause 96, wherein the therapeutic component is an antimicrobial agent.98. The hydrogel coated surgical mesh of clause 96, wherein the therapeutic component is an antibiotic agent.99. The method of any one of clauses 29-38, wherein the bending of the mesh results in no more than 20%, 15%, 10%, 5%, or 2% loss of therapeutic component.100. The method of clause 99, wherein the therapeutic component is an antimicrobial agent.101. The method of clause 100, wherein the therapeutic component is an antibiotic agent.

Claims

Claims:

1. A hydrogel coated surgical mesh comprising: (1) a biocompatible mesh matrix, and (2) a hydrogel polymer composition; said hydrogel polymer composition comprising (a) hyaluronan, (b) methylcellulose, and (c) a therapeutically effective amount of at least one therapeutic component; wherein said mesh matrix is coated with said hydrogel polymer composition and wherein said therapeutic component is selected from the group consisting of an antimicrobial agent, an anti-inflammatory agent, an angiogenesis promoter, and any combination thereof.

2. The hydrogel coated surgical mesh of claim 1 wherein the surgical mesh matrix comprises a synthetic polymer.

3. The hydrogel coated surgical mesh of claim 2 wherein the synthetic polymer comprises at least one non-biodegradable polymer.

4. The hydrogel coated surgical mesh of claim 3 wherein the non-biodegradable polymer is selected from the group consisting of polypropylene, expanded polytetrafluoroethylene, polyester, polyvinylidene fluoride, nylon, and any combination thereof.

5. The hydrogel coated surgical mesh of claim 4 wherein the non-biodegradable polymer is polypropylene.

6. The hydrogel coated surgical mesh of claim 2 wherein the synthetic polymer comprises at least one biodegradable polymer.

7. The hydrogel coated surgical mesh of claim 6 wherein the biodegradable polymer is selected from the group consisting of polyglycolic acid, polylactic acid, polydioxanone, poly-4-hydroybutyrate, polyglycolide-co-lactide, polycaprolactone, and trimethylene carbonate.

8. The hydrogel coated surgical mesh of claim 7 wherein the biodegradable polymer is poly-4-hydrobutyrate.

9. The hydrogel coated surgical mesh of any one of claims 1-8 wherein the surgical mesh matrix comprises at least one natural polymer.

10. The hydrogel coated surgical mesh of claim 9 wherein the natural polymer is selected from the group consisting of collagen, silk fibroin, chitosan, and decellularized extra cellular matrix.

11. The hydrogel coated surgical mesh of any one of claims 1-10 wherein the anionic polymer is selected from the group consisting of hyaluronan (HA), derivatives of hyaluronan, alginate, derivatives of alginate, carboxymethyl cellulose (CMC), carboxyethyl cellulose (CEC), derivatives of hydroxypropyl cellulose (HPC), derivatives of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl methyl cellulose phthalate (HPMCP), sodium carboxymethyl cellulose (Na-CMC), phosphorylated cellulose, sulfated cellulose, acrylates, C 10-30 alkyl acrylate crosspolymer, carbomer, polyacrylic acid (PAA), poly(methacryclic acid) and mixtures thereof.

12. The hydrogel coated surgical mesh of any one of claims 1-11 wherein the anionic polymer is hyaluronan.

13. The hydrogel coated surgical mesh of any one of claims 1-12 wherein the inverse thermal gelling polymer is selected from the group consisting of methylcellulose, a chitosan and p-glycerophosphate solution, collagen, tri-block copolymer of polyethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol), tri-block copolymer of polypropylene glycol)-poly(ethylene glycol)-poly (propylene glycol), poly(N-isopropyl acrylamide), agarose, copolymers of poly-N-isopropylacrylamide, polysaccharides and mixtures thereof.

14. The hydrogel coated surgical mesh of any one of claims 1-13 wherein the inverse thermal gelling polymer is methylcellulose.

15. The hydrogel coated surgical mesh of claim 12 wherein the hyaluronan is present from 0.5-3% (wt / wt) of the hydrogel polymer matrix.

16. The hydrogel coated surgical mesh of claim 14 wherein the methylcellulose is present from 0.5-8% (wt / wt) of the hydrogel polymer matrix.

17. The hydrogel coated surgical mesh of any one of claims 1-16 wherein the anionic polymer is hyaluronan and the inverse thermal gelling polymer is methylcellulose and the ratio of hyaluronammethylcellulose in the hydrogel polymer matrix is from 1:1 - 1:7 (wt / wt).

18. The hydrogel coated surgical mesh of claim 17 wherein the ratio of hyaluronammethylcellulose is 1:1 (wt / wt).

19. The hydrogel coated surgical mesh of claim 17 wherein the ratio of hyaluronammethylcellulose is 1.4:2 (wt / wt).

20. The hydrogel coated surgical mesh of claim 17 wherein the ratio of hyaluronammethylcellulose is 2:7 (wt / wt).

21. The hydrogel coated surgical mesh of any one of claims 1-20 wherein the at least one therapeutic component is selected from the group consisting of an anti-inflammatory agent, an angiogenesis promoter, an antimicrobial agent, and any combination thereof.

22. The hydrogel coated surgical mesh of claim 21 wherein the antimicrobial agent is selected from the group consisting of an antibiotic agent, an antifungal compound, a nonantibiotic antiseptic, a broad-spectrum antimicrobial, an antimicrobial peptide, and any combination thereof.

23. The hydrogel coated surgical mesh of claim 22 wherein the antibiotic agent is selected from the group consisting of p-lactams, glycopeptides, lipoglycopeptides, macrolides, tetracyclines, aminoglycosides, fluroquinolones, folate pathway inhibitors, oxazolidinones, lincosamides, rifamycins, nitroimidazoles, polypeptide antibiotics, and any combination thereof.

24. The hydrogel coated surgical mesh of claim 22 wherein the antibiotic agent is selected from the group consisting of gentamicin, vancomycin, ciprofloxacin, amoxicillin-clavulanic acid, cefazolin, amikacin, colisitin, rifampin, minocycline, metronidazole, tobramycin, erythromycin, tetracycline, their respective pharmaceutically acceptable salts, and any combination thereof.

25. The hydrogel coated surgical mesh of claim 21 wherein the anti-inflammatory agent is selected from the group consisting of dexamethasone, prednisolone, triamcinolone acetonide, ketorolac, ibuprofen, celecoxib, tacrolimus, pirfenidone, lnterleukin-1, curcumin, resveratrol, and any combination thereof.

26. The hydrogel coated surgical mesh of claim 21 wherein the angiogenesis promoter is selected from the group consisting of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDFGF), angiopoietin Ang-1, angiopoietin Ang-2, lnterleukin-8 (IL-8) , granulocyte-macrophage colony-stimulating factor (GM-CSF), collagen, heparin, thalidomide derivatives, prostaglandin E1 (PGE1), dimethyloxalyglycine (DMOG), exosomes from mesenchymal stem cells (MSCs), plateletrich plasma (PRP), angiomodulin, erythropoietin, and any combination thereof.

27. The hydrogel coated surgical mesh of any one of claims 22-24 wherein the antibiotic agent is present in both its acidic and basic form.

28. The hydrogel coated surgical mesh of claim 27 wherein the acidic form of the antibiotic agent provides for an immediate release of the antibiotic agent and the basic form of the antibiotic agent provides for a controlled release of the antibiotic agent for at least one week at body temperature.

29. A method for treating a hernia in a patient, comprising:(a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning the surgical mesh at or near the site of the hernia; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the hernia, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one therapeutic component.

30. The method of claim 29 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-28.

31. A method of treating a surgical site infection in a patient in need thereof, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.

32. The method of claim 31 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of claims 1-28.

33. A method of treating a surgical site infection in a patient treated for hernia, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition,(b) positioning at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.

34. The method of claim 33 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of claims 1-28.

35. A method of prophylactically preventing a surgical site infection in a patient, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.

36. The method of claim 35 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of claims 1-28.

37. A method of prophylactically preventing a surgical site infection in a patient treated for hernia, comprising: (a) providing a surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition, (b) positioning at or near the site of the surgery; and (c) securing the surgical mesh to surrounding tissue to reinforce the site of the surgery, wherein the hydrogel polymer composition comprises: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antimicrobial agent.

38. The method of claim 37 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of claims 1-28.

39. Use of the hydrogel coated surgical mesh of any one of clauses 1-28 for the treatment of hernia in a patient in need thereof.

40. Use of the hydrogel coated surgical mesh of any one of clauses 1-28 for the treatment of surgical site infection in a patient in need thereof.

41. Use of the hydrogel coated surgical mesh of any one of clauses 1-28 for the treatment of surgical site infection in a patient treated for hernia repair surgery.

42. Use of the hydrogel coated surgical mesh of any one of clauses 1-28 for prophylactically preventing surgical site infection in a patient in need thereof.

43. Use of the hydrogel coated surgical mesh of any one of clauses 1-28 for prophylactically preventing surgical site infection in a patient treated for hernia repair surgery44. A surgical hernia mesh kit comprising:(a) a surgical mesh comprising a biocompatible material coated with a hydrogel polymer composition, b) one or more surgical instruments for positioning and securing the mesh at the site of the hernia, and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh and the placement and fixation of the surgical mesh in a subject in need thereof, wherein the hydrogel polymer composition comprises: (i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one therapeutic component.

45. The kit of claim 44 wherein the surgical mesh comprises the hydrogel coated surgical mesh of any one of clauses 1-28.

46. Use of the kit of any one of claims 44-45 for the treatment of hernia repair surgery in a patient in need thereof.

47. Use of the kit of any one of claims 44-45 for the treatment of surgical site infection in a patient in need thereof.

48. Use of the kit of any one of claims 44-45 for the treatment of surgical site infection in a patient treated for hernia repair surgery.

49. Use of the kit of any one of claims 44-45 for prophylactically preventing a surgical site infection in a patient treated for hernia repair surgery.

50. Use of the kit of any one of claims 44-45 for prophylactically preventing a surgical site infection in a patient in need thereof.

51. A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of at least one therapeutic component, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of hernia repair surgery and the therapeutic benefits provided by the hydrogel polymer coating.

52. A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising atherapeutically effective amount of at least one antimicrobial agent, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of surgical site infection or for prophylactically preventing surgical site infections and the therapeutic benefits provided by the hydrogel polymer coating.

53. A pharmaceutical package comprising: a) a sterile surgical mesh comprising a biocompatible matrix coated with a hydrogel polymer composition comprising a therapeutically effective amount of at least one antimicrobial agent, b) a sealed container housing the surgical mesh to maintain sterility and, optionally, c) instructions for use, detailing one or more of sterile handling of the surgical mesh, the application of the surgical mesh for the treatment of surgical site infection or for prophylactically preventing surgical site infections for a patient treated for hernia repair surgery and the therapeutic benefits provided by the hydrogel polymer coating.

54. The pharmaceutical package of any one of claims 51-53 wherein the surgical mesh comprises the synthetic polymer of any one of claims 3-8.

55. The pharmaceutical package of any one of claims 51-53 wherein the surgical mesh comprises the natural polymer of claim 10.

56. The pharmaceutical package of claims 51-53 wherein the hydrogel polymer composition comprises the anionic gelling polymer and the inverse thermal gelling polymer of any one of claims 11-20.

57. The pharmaceutical package of claim 51 wherein the therapeutic component comprises any one of the therapeutic components of claims 21-28.

58. The pharmaceutical package of any one of clauses 53-54 wherein the antimicrobial agent comprises the antibiotic agent of claim 23.

59. The pharmaceutical package of claim 51 wherein the therapeutic component comprises an antibiotic agent of claim 23 in combination with an anti-inflammatory agent of claim 25.

60. The pharmaceutical package of claim 51 wherein the therapeutic component comprises an antibiotic agent of claim 23 in combination with an angiogenesis promoter of claim 26.

61. The pharmaceutical package of claim 51 wherein the therapeutic component comprises an antibiotic agent in combination with an anti-inflammatory agent of claim 25 and an angiogenesis promoter of claim 26.

62. The pharmaceutical package of claims 52-53 wherein the hydrogel polymer composition further comprises an anti-inflammatory agent of claim 25.

63. The pharmaceutical package of claims 52-53 wherein the hydrogel polymer composition further comprises an angiogenesis promoter of clause 26.

64. The pharmaceutical package of claims 52-53 wherein the hydrogel polymer composition further comprises an anti-inflammatory agent of claim 25 in combination with an angiogenesis promoter of claim 26.

65. The pharmaceutical package of claims 52-53 wherein the antibiotic is selected from the group consisting of cefazolin, vancomycin, erythromycin, tetracycline, and any combination thereof.

66. A method of manufacturing a surgical mesh comprising: (a) providing a biocompatible matrix; (b) coating the biocompatible matrix with a hydrogel polymer composition comprising: i) an anionic gelling polymer, (ii) an inverse thermal gelling polymer, and (iii) a therapeutically effective amount of at least one antibiotic agent; and (c) drying the hydrogel polymer coating.

67. The method of claim 66 further comprising drying the hydrogel polymer coating for at least 20 hours, optionally at a temperature of between about 30°C and about 45°C.

68. The method of claim 67, further comprising incubating the hydrogel polymer coating at a temperature of between 1 °C and 4°C for a period of 2 and 6 hours prior to drying.

69. The method of any one of claims 66-68 further comprising physically blending the anionic gelling polymer and the inverse thermal gelling polymer and dispersing the at least one antibiotic agent therein.

70. The hydrogel coated surgical mesh of any one of claims 1-28, wherein at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or 100% of the therapeutic component is released within 24 hours of application at the site of surgery at physiological temperature.

71. The hydrogel coated surgical mesh of any one of claims 1-28, wherein no more than 60%, no more than 50%, no more than 40%, no more than 30%, or no more than 20% of the therapeutic component is released within 1 hour of application.

72. The hydrogel coated surgical mesh of any one of claims 1-28, wherein no more than 95%, no more than 90%, or no more than 80% of the therapeutic component is released within 3 hours of application.

73. The hydrogel coated surgical mesh of any one of claims 1-28, wherein at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the therapeutic component is released within 6 hours of application.

74. The hydrogel coated surgical mesh of any one of claims 1-28, wherein the hydrogel polymer composition provides an early bolus release of therapeutic component within 1 hour to reduce bacterial burden.

75. The hydrogel coated surgical mesh of claim 74, wherein the bolus release comprises at least 20%, at least 30%, or at least 40% of the total therapeutic component.

76. The hydrogel coated surgical mesh of any one of claims 70-75, wherein the therapeutic component comprises an antimicrobial agent.

77. The hydrogel coated surgical mesh of any one of claims 70-75, wherein the therapeutic component comprises an antibiotic agent.

78. The method of any one of claims 29-38, wherein at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or 100% of the therapeutic component is released from the hydrogel polymer composition within 24 hours of application at the site of surgery.

79. The method of any one of claims 29-38, wherein no more than 60%, no more than 50%, no more than 40%, no more than 30%, or no more than 20% of the therapeutic component is released within 1 hour of application.

80. The method of any one of claims 29-38, wherein no more than 95%, no more than 90%, or no more than 80% of the therapeutic component is released within 3 hours of application.

81. The method of any one of claims 29-38, wherein at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the therapeutic component is released within 6 hours of application.

82. The method of any one of claims 29-38, wherein the hydrogel polymer composition provides an early bolus release of therapeutic component within 1 hour to reduce bacterial burden.

83. The method of claim 82, wherein the bolus release comprises at least 20%, at least 30%, or at least 40% of the total therapeutic component.

84. The method of any one of claims 78-83, wherein the therapeutic component comprises an antimicrobial agent.

85. The method of any one claims 78-83, wherein the therapeutic component comprises an antibiotic agent.

86. The hydrogel coated surgical mesh of any one of claims 1-28, wherein the therapeutic component is present at 1-20% (wt / wt), 2-18% (wt / wt), 3-15% (wt / wt), 5-15% (wt / wt) or 6-8 % (wt / wt) of the hydrogel polymer composition.

87. The hydrogel coated surgical mesh of claim 86, wherein the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition.

88. The hydrogel coated surgical mesh of any one of claims 86-87, wherein the therapeutic component comprises an antimicrobial agent.

89. The hydrogel coated surgical mesh of any one of claims 86-87, wherein the therapeutic component comprises an antibiotic agent.

90. The hydrogel coated surgical mesh of any one of claims 1-28, wherein the therapeutic component comprises a combination of an antibiotic agent, an anti-inflammatory agent, and / or an angiogenesis promoter, and wherein the combined therapeutic component loading is 33% (wt / wt) of the hydrogel polymer composition, with each therapeutic agent independently present at 1-15% (wt / wt).

91. The method of any one of claims 29-38, wherein the hydrogel polymer composition comprises a therapeutic component present at 1-20% (wt / wt), 2-18% (wt / wt), 3-15% (wt / wt), 5-15% (wt / wt), or 6-8% (wt / wt) of the hydrogel polymer composition.

92. The method of claim 91 , wherein the therapeutic component is present at 7.5% (wt / wt) of the hydrogel polymer composition.

93. The method of any one of claims 91-92, wherein the therapeutic component comprises an antimicrobial agent.

94. The method of any one of claims 91-92, wherein the therapeutic component comprises anantibiotic agent.

95. The method of any one of claims 29-38, wherein the therapeutic component comprises a combination of an antibiotic agent, an anti-inflammatory agent, and / or an angiogenesis promoter, and wherein the combined therapeutic component loading is 3-30% (wt / wt) of the hydrogel polymer composition, with each therapeutic agent independently present at 1-15% (wt / wt).

96. The hydrogel coated surgical mesh of any one of claims 1-28, wherein bending of the mesh results in no more than 20%, 15%, 10%, 5%, or 2% loss of therapeutic component.

97. The hydrogel coated surgical mesh of claim 96, wherein the therapeutic component is an antimicrobial agent.

98. The hydrogel coated surgical mesh of claim 96, wherein the therapeutic component is an antibiotic agent.

99. The method of any one of claims 29-38, wherein the bending of the mesh results in no more than 20%, 15%, 10%, 5%, or 2% loss of therapeutic component.

100. The method of claim 99, wherein the therapeutic component is an antimicrobial agent.

101. The method of clause 100, wherein the therapeutic component is an antibiotic agent.

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