Drug-eluting implant

Last updated
Polymer implant eluting drugs Polymer implant eluting drugs.png
Polymer implant eluting drugs

Drug eluting implants encompass a wide range of bioactive implants that can be placed in or near a tissue to provide a controlled, sustained or on demand release of drug while overcoming barriers associated with traditional oral and intravenous drug administration, such as limited bioavailability, metabolism, and toxicity. [1] These implants can be used to treat location-specific and surrounding illness and commonly use 3D printing technologies to achieve individualized implants for patients. [2]

Contents

The production of drug eluting implants has grown significantly in the last decade and continues to be an area of research due to their flexible nature that can be utilised for the treatment of a multitude of medical conditions. [3] These implants can be loaded with a variety of different drug types such as antibiotics, antivirals, chemotherapy, growth factors and anti-inflammatory drugs. [4]

Drug eluting implants can provide a versatile method of drug delivery that can be personalized and targeted to treat a variety of medical conditions and overcome issues such as drug bioavailability, metabolism and dosage associated with traditional drug delivery systems. [5]

Applications

Drug eluting implants can be used in the management and treatment of a variety of medical conditions. Traditional drug delivery methods have potential disadvantages that have led to the development of different drug delivery techniques across most body systems, many of which can improve treatment efficacy. [1]

Cardiovascular

Drug-eluting stents and balloons are a common therapeutic method in the management and treatment of cardiovascular disease that to open and maintain arteries while delivering drug locally to an area of a vessel. [1] [2]

Gynecology

Common gynecological implants that elute contraceptive medication can be inserted subcutaneously or into the uterus. Non-invasive drug eluting ring implants that can be inserted into the vagina and release therapeutic doses of contraceptive, anti-inflammatory and antibiotic drugs to increase compliance of contraceptive therapeutics are under development. [1] [6]

3-D rendering of a bone joint with a drug eluting coating. 3D rendering of bone joint with drug-eluting coating.png
3-D rendering of a bone joint with a drug eluting coating.

Orthopedics

The treatment of orthopedic conditions has proved to be a large target area for drug eluting implants. Current uses for this method drug delivery include bone and joint implants that can release drugs at the joint replacement sites to prevent infection and anti-inflammatory responses. [7]

Other potential treatments using this method of drug delivery in orthopedic medicine include drug eluting implants that aid in the regeneration of bone at implantation sites while reducing microbial growth. [8]

Oncology

Current treatment for oncological conditions include chemotherapy, radiation and surgery. [9] Drug eluting implants have shown potential in the treatment of cancer through adjuvant chemotherapy that has shown to suppress tumor formation locally, overcoming side effects associated with systemic chemotherapy treatment and reduce the need for surgical resection of cancerous tumors. [10]

Ophthalmology

Intravitreal administration of therapeutic drug doses is commonly done via injection or implant. [11] Drug eluting contact lenses and implants can deliver targeted and extended doses of drug to the retina without the need for injection. [12]

Dermatology

Drug eluting sutures can produce a prolonged local release of anaesthetic as well as heal wounds. This has the potential to limit the need for postoperative opioid analgesics that can cause addiction. [13]

Design

Drug eluting implants are designed to be implanted into location specific tissues and release drug locally. These implants are made using biocompatible materials that will not elicit an immune response. [14]

The structure of the implant is individualized and designed to conform to the shape of the tissue that is being treated. The implant contains a reservoir that elutes a drug dependent on the mechanism of release. This mechanism be in the form of a matrix coating of the implant or a reservoir within the implant. [15] Designs aim to provide therapeutic dosage to the target tissue while reducing negative side effects and maximizing efficacy. [15]

Development and Manufacturing

There are a variety of methods used in the manufacturing of drug eluting implants, most of which utilize 3D printing technology. Techniques are dependent on factors such as the condition being managed, the drug being released and the individual patient being treated. [5]

3D Printing

3D printing involves the production of a 3-dimensional object through the layering of material. There are a variety of 3D printing techniques, all of which come with their own advantages and disadvantages which should be considered when creating an individualized implant. The production of these drug eluting implants through 3D printing is currently being investigated to determine drug delivery properties and efficacy to improve individualized medicinal devices. [5]

Inkjet 3-D printer used for production of drug-eluting implants Inkjet 3-D printer used for production of drug-eluting implants.png
Inkjet 3-D printer used for production of drug-eluting implants

Traditional bio-printing technologies used in the field of biomedical engineering include inkjet-based systems, extrusion-based systems, and laser-assisted systems that can be used to create highly specific and individual implants for patients. [4]

Materials

The most common materials used to create drug eluting implants include highly versatile polymers, ceramics, and metals, all with varying kinetics that can be manipulated to produce the desired drug delivery effect. [5] [16]

Polymers

Polymers and polymer networks are among the most widely used materials in drug eluting implants. These implants are classified as either degradable and able to be broken down and metabolized by the body, or non-degradable which eventually require removal. [2]

Common degradable polymer materials used in drug eluting implants include poly e-caprolactone (PCL), polylactic-co-glycolic acid (PLGA) and poly-L-lactic acid (PLLA), while non-degradable polymer materials include silicones commonly used in plastic surgery, urethanes and acrylates, and are more likely to be used in the treatment of chronic conditions in which long term implantation is to be expected. [2]

Polymers can be used to create monolithic drug delivery systems in which a drug is released in a rate-controlled polymer matrix, reservoir drug delivery systems containing a drug-filled core that releases drug in a manner dependent on the surrounding polymer, and hydrogels that can release drugs controlled by a variety of stimuli including ultrasound, temperature, and pH changes. [2] [16] [17]

Ceramics

In relation to biomedical implant manufacturing, the term 'ceramic' can be used to encompass a wide variety of non-metallic substances that can be utilised in drug eluting implants due to their biocompatible properties such as resistance to corrosion and shear, low electrical conductance ability, and high melting temperatures. [18] [19]

Ceramic implants can be classified as bio-inert and include materials such as aluminum, zirconia, and certain carbon and silicon derivatives which are not biodegradable. Bioactive ceramic implants are biodegradable substances that include calcium phosphates, and a variety of oxidised minerals that mimic natural bone properties. Ceramic drug eluting implants are therefore commonly used in hard tissue replacement surgeries such as bone. [18] [19]

Metals

Metals such as titanium are highly biocompatible and therefore commonly used in osteopathic medicine in the manufacturing of artificial joints. These joints are often coated in polymeric, or ceramic material embedded with drugs for prevention of infection and rejection, and to reduce inflammatory responses that are common among joint implants. [20]

Metals however are susceptible to erosion and infection and lack biological activity. When metals are used as an implant as opposed to a permanent mechanical fixture, problems can arise when contacting associated bone and releasing drug to target tissues such as static stresses that can lead to bone loss at the site of implantation. [4]

Drug Loading

The idea of a drug eluting implant is to overcome many of the obstacles associated with traditional drug therapies, as well as reducing the need for potentially invasive procedures, including those involved in the removal of embedded drug eluting implants. [5]

The loading of a drug onto a matrix can be either incorporated into the drug at the time of manufacture or performed after the printing of an implant is complete. Drugs integrated at the point of manufacture through blending with polymeric materials are generally able to withstand preparation conditions which can exclude many sensitive drugs from this mechanism. Therefore, loading after manufacture is considered to be an easier method. [5]

Normally, once drug is loaded into a delivery system, there is no non-invasive way to refill once drug levels in the system are depleted. Developments in drug delivery refilling have shown potential through chemically modified drug-loaded hydrogels that, once in the body, are able to translocate to a specific local drug delivery depot as a non-invasive means of refilling. [21]

Advantages

Drug eluting implants aim to improve efficacy of drug delivery by overcoming issues commonly associated with traditional systemic administration of drugs such as metabolism, toxicity, and an inability to maintain a certain concentration of drug in the circulation. To overcome these issues, patients are usually administered higher doses of drugs in a controlled and clinical setting. [1]

The introduction of a drug eluting implant to a local tissue can provide targeted and sustained dosing of drug and prevent systemic metabolism, a common obstacle seen in orally delivered medications. This can reduce dosage which can in turn reduce treatment cost. Lower drug concentrations delivered via local depots can therefore lower the risk of toxicity as well as increasing compliance and reducing physician/patient burden to manage appropriate drug concentrations. [15] [18]

Drug eluting implants also provide an effective mechanism for bypassing the blood-brain barrier, and this method of drug delivery is primarily used in the treatment of glial tumors. [15]

Limitations

There are issues that can arise with the local and targeted method of drug eluting implants. [1] One of the largest obstacles that the field of drug eluting implants faces is the mechanism of drug loading and reloading of non-biodegradable implants. The development of drugs that can travel from systemic circulation to a specific depot could prove a useful way to overcome the need for invasive refilling and re-implantation. [15] [21]

Foreign bodies implanted into the body can elicit immune responses. Medically implanted drug eluting devices can induce an inflammatory response as well as being rejected by the body which can cause chronic inflammation. [22] Anti-inflammatory drugs can be administered alongside the implantation of a drug eluting device to prevent chronic inflammation and systemic immune side effects that this may induce. [4]

Future of drug eluting implants

The field of drug eluting implants is expanding to encompass treatment and management methods for a variety of treatments. In the future, possibilities exist to manufacture 'smart' drug eluting implants fitted with sensors that can provide feedback-controlled drug delivery in patients suffering from abnormalities such as diabetes, or for patients that experience seizures and require prophylactic treatment. [15]

The development of novel drug eluting implant materials and mechanisms has the potential for improving patient safety, comfort, compliance and thus acting on global health challenges such as chronic diseases, infectious and non-infectious diseases, and contraception. [14]

Related Research Articles

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

<span class="mw-page-title-main">Tissue engineering</span> Biomedical engineering discipline

Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.

<span class="mw-page-title-main">Implant (medicine)</span> Device surgically placed within the body for medical purposes

An implant is a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. For example, an implant may be a rod, used to strengthen weak bones. Medical implants are human-made devices, in contrast to a transplant, which is a transplanted biomedical tissue. The surface of implants that contact the body might be made of a biomedical material such as titanium, silicone, or apatite depending on what is the most functional. In 2018, for example, American Elements developed a nickel alloy powder for 3D printing robust, long-lasting, and biocompatible medical implants. In some cases implants contain electronics, e.g. artificial pacemaker and cochlear implants. Some implants are bioactive, such as subcutaneous drug delivery devices in the form of implantable pills or drug-eluting stents.

<span class="mw-page-title-main">Polycaprolactone</span> Chemical compound

Polycaprolactone (PCL) is a synthetic, semi-crystalline, biodegradable polyester with a melting point of about 60 °C and a glass transition temperature of about −60 °C. The most common use of polycaprolactone is in the production of speciality polyurethanes. Polycaprolactones impart good resistance to water, oil, solvent and chlorine to the polyurethane produced.

<span class="mw-page-title-main">Bioglass 45S5</span> Bioactive glass biomaterial

Bioglass 45S5 or calcium sodium phosphosilicate, is a bioactive glass specifically composed of 45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, and 6.0 wt% P2O5. Typical applications of Bioglass 45S5 include: bone grafting biomaterials, repair of periodontal defects, cranial and maxillofacial repair, wound care, blood loss control, stimulation of vascular regeneration, and nerve repair.

<span class="mw-page-title-main">Organ printing</span> Method of creating artificial organs

Organ printing utilizes techniques similar to conventional 3D printing where a computer model is fed into a printer that lays down successive layers of plastics or wax until a 3D object is produced. In the case of organ printing, the material being used by the printer is a biocompatible plastic. The biocompatible plastic forms a scaffold that acts as the skeleton for the organ that is being printed. As the plastic is being laid down, it is also seeded with human cells from the patient's organ that is being printed for. After printing, the organ is transferred to an incubation chamber to give the cells time to grow. After a sufficient amount of time, the organ is implanted into the patient.

<span class="mw-page-title-main">Drug-eluting stent</span> Medical implant

A drug-eluting stent (DES) is a tube made of a mesh-like material used to treat narrowed arteries in medical procedures both mechanically and pharmacologically. A DES is inserted into a narrowed artery using a balloon. Once the balloon inside the stent is inflated, the stent expands, pushing against the artery wall, keeping the artery open, thereby improving blood flow. The mesh design allows cells to grow through and around it, securing it in place.

<span class="mw-page-title-main">Biomaterial</span> Any substance that has been engineered to interact with biological systems for a medical purpose

A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose – either a therapeutic or a diagnostic one. The corresponding field of study, called biomaterials science or biomaterials engineering, is about fifty years old. It has experienced steady growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.

<span class="mw-page-title-main">Foreign body reaction</span> Medical condition

A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells, fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.

Neural tissue engineering is a specific sub-field of tissue engineering. Neural tissue engineering is primarily a search for strategies to eliminate inflammation and fibrosis upon implantation of foreign substances. Often foreign substances in the form of grafts and scaffolds are implanted to promote nerve regeneration and to repair damage caused to nerves of both the central nervous system (CNS) and peripheral nervous system (PNS) by an injury.

Nano-scaffolding or nanoscaffolding is a medical process used to regrow tissue and bone, including limbs and organs. The nano-scaffold is a three-dimensional structure composed of polymer fibers very small that are scaled from a Nanometer scale. Developed by the American military, the medical technology uses a microscopic apparatus made of fine polymer fibers called a scaffold. Damaged cells grip to the scaffold and begin to rebuild missing bone and tissue through tiny holes in the scaffold. As tissue grows, the scaffold is absorbed into the body and disappears completely.

<span class="mw-page-title-main">Artificial bone</span> Bone-like material

Artificial bone refers to bone-like material created in a laboratory that can be used in bone grafts, to replace human bone that was lost due to severe fractures, disease, etc.

<span class="mw-page-title-main">Bioresorbable stent</span> Medical stent that dissolves or is absorbed by the body

A bioresorbable stent is a tube-like device (stent) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents.

Octacalcium phosphate (sometimes referred to as OCP) is a form of calcium phosphate with formula Ca8H2(PO4)6·5H2O. OCP may be a precursor to tooth enamel, dentine, and bones. OCP is a precursor of hydroxyapatite (HA), an inorganic biomineral that is important in bone growth. OCP has garnered lots of attention due to its inherent biocompatibility. While OCP exhibits good properties in terms of bone growth, very stringent synthesis requirements make it difficult for mass productions, but nevertheless has shown promise not only in-vitro, but also in in-vivo clinical case studies.

Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ (in its original position or place) tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system.

Professor Alastair J Sloan is an applied bioscientist and expert in the broad field of mineralised connective tissues, and since January 2020 current head of the Melbourne Dental School, University of Melbourne.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

Bioprinting drug delivery is a method for producing drug delivery vehicles. It uses three-dimensional printing of biomaterials via additive manufacturing. Such vehicles are biocompatible, tissue-specific hydrogels or implantable devices. 3D bioprinting prints cells and biological molecules to form tissues, organs, or biological materials in a scaffold-free manner that mimics living human tissue. The technique allows targeted disease treatments with scalable and complex geometry.

Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.

Microneedles (MNs) are medical instruments for the procedure of microneedling that are most commonly used in drug delivery, disease diagnosis, and collagen induction therapy. They are known for being minimally invasive and precise. MNs consist of arrays of micro-sized needles ranging from 25μm-2000μm. The concept of microneedling was first established in the 1970s, but its popularity began to rise as they have been found to be effective in drug delivery and possess cosmetic benefits.

References

  1. 1 2 3 4 5 6 Quarterman, Juliana C.; Geary, Sean M.; Salem, Aliasger K. (February 2021). "Evolution of drug-eluting biomedical implants for sustained drug delivery". European Journal of Pharmaceutics and Biopharmaceutics. 159: 21–35. doi:10.1016/j.ejpb.2020.12.005. PMC   7856224 . PMID   33338604.
  2. 1 2 3 4 5 Rykowska, I.; Nowak, I.; Nowak, R. (2020-10-11). "Drug-Eluting Stents and Balloons—Materials, Structure Designs, and Coating Techniques: A Review". Molecules. 25 (20): 4624. doi: 10.3390/molecules25204624 . ISSN   1420-3049. PMC   7594099 . PMID   33050663.
  3. ↑ Gao, Jingjing; Karp, Jeffrey M; Langer, Robert; Joshi, Nitin (2023-01-24). "The Future of Drug Delivery". Chemistry of Materials. 35 (2): 359–363. doi: 10.1021/acs.chemmater.2c03003 . ISSN   0897-4756. PMC   10553157 . PMID   37799624. S2CID   256262291.
  4. 1 2 3 4 Alshimaysawee, Sadeq; Fadhel Obaid, Rasha; Al-Gazally, Moaed E.; Alexis Ramírez-Coronel, Andrés; Bathaei, Masoud Soroush (January 2023). "Recent Advancements in Metallic Drug-Eluting Implants". Pharmaceutics. 15 (1): 223. doi: 10.3390/pharmaceutics15010223 . ISSN   1999-4923. PMC   9862589 . PMID   36678852.
  5. 1 2 3 4 5 6 Domsta, Vanessa; Seidlitz, Anne (January 2021). "3D-Printing of Drug-Eluting Implants: An Overview of the Current Developments Described in the Literature". Molecules. 26 (13): 4066. doi: 10.3390/molecules26134066 . ISSN   1420-3049. PMC   8272161 . PMID   34279405.
  6. ↑ Rafiei, Fojan; Tabesh, Hadi; Farzad, Shayan; Farzaneh, Farah; Rezaei, Maryam; Hosseinzade, Fateme; Mottaghy, Khosrow (July 2021). "Development of Hormonal Intravaginal Rings: Technology and Challenges". Geburtshilfe und Frauenheilkunde. 81 (7): 789–806. doi:10.1055/a-1369-9395. ISSN   0016-5751. PMC   8277443 . PMID   34276064.
  7. ↑ Suhardi, V. J.; Bichara, D. A.; Kwok, S. J. J.; Freiberg, A. A.; Rubash, H.; Malchau, H.; Yun, S. H.; Muratoglu, O. K.; Oral, E. (2017-06-13). "A fully functional drug-eluting joint implant". Nature Biomedical Engineering. 1 (6): 1–11. doi:10.1038/s41551-017-0080. ISSN   2157-846X. PMC   5773111 . PMID   29354321.
  8. ↑ Bagherifard, Sara (2017-02-01). "Mediating bone regeneration by means of drug eluting implants: From passive to smart strategies" . Materials Science and Engineering: C. 71: 1241–1252. doi:10.1016/j.msec.2016.11.011. ISSN   0928-4931. PMID   27987680. Archived from the original on 2023-04-19. Retrieved 2023-04-19.
  9. ↑ Debela, Dejene Tolossa; Muzazu, Seke GY; Heraro, Kidist Digamo; Ndalama, Maureen Tayamika; Mesele, Betelhiem Woldemedhin; Haile, Dagimawi Chilot; Kitui, Sophia Khalayi; Manyazewal, Tsegahun (January 2021). "New approaches and procedures for cancer treatment: Current perspectives". SAGE Open Medicine. 9: 205031212110343. doi:10.1177/20503121211034366. ISSN   2050-3121. PMC   8366192 . PMID   34408877.
  10. ↑ Exner, Agata A; Saidel, Gerald M (2008-07-01). "Drug-eluting polymer implants in cancer therapy" . Expert Opinion on Drug Delivery. 5 (7): 775–788. doi:10.1517/17425247.5.7.775. ISSN   1742-5247. PMID   18590462. S2CID   137675666. Archived from the original on 2024-03-16. Retrieved 2023-04-19.
  11. ↑ Kim, Hyeong Min; Woo, Se Joon (2021-01-15). "Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives". Pharmaceutics. 13 (1): 108. doi: 10.3390/pharmaceutics13010108 . ISSN   1999-4923. PMC   7830424 . PMID   33467779.
  12. ↑ Ross, Amy E.; Bengani, Lokendrakumar C.; Tulsan, Rehka; Maidana, Daniel E.; Salvador-Culla, Borja; Kobashi, Hidenaga; Kolovou, Paraskevi E.; Zhai, Hualei; Taghizadeh, Koli; Kuang, Liangju; Mehta, Manisha; Vavvas, Demetrios G.; Kohane, Daniel S.; Ciolino, Joseph B. (2019-10-01). "Topical sustained drug delivery to the retina with a drug-eluting contact lens". Biomaterials. 217: 119285. doi: 10.1016/j.biomaterials.2019.119285 . ISSN   0142-9612. PMID   31299627. S2CID   196349778.
  13. ↑ Weldon, Christopher B.; Tsui, Jonathan H.; Shankarappa, Sahadev A.; Nguyen, Vy T.; Ma, Minglin; Anderson, Daniel G.; Kohane, Daniel S. (2012-08-10). "Electrospun drug-eluting sutures for local anesthesia". Journal of Controlled Release. 161 (3): 903–909. doi:10.1016/j.jconrel.2012.05.021. hdl:1721.1/101125. ISSN   0168-3659. PMC   3412890 . PMID   22609349.
  14. 1 2 Johnson, Ashley R.; Forster, Seth P.; White, David; Terife, Graciela; Lowinger, Michael; Teller, Ryan S.; Barrett, Stephanie E. (2021-05-04). "Drug eluting implants in pharmaceutical development and clinical practice" . Expert Opinion on Drug Delivery. 18 (5): 577–593. doi:10.1080/17425247.2021.1856072. ISSN   1742-5247. PMID   33275066. S2CID   227282368. Archived from the original on 2023-04-19. Retrieved 2023-04-19.
  15. 1 2 3 4 5 6 Fayzullin, Alexey; Bakulina, Alesia; Mikaelyan, Karen; Shekhter, Anatoly; Guller, Anna (2021-12-09). "Implantable Drug Delivery Systems and Foreign Body Reaction: Traversing the Current Clinical Landscape". Bioengineering. 8 (12): 205. doi: 10.3390/bioengineering8120205 . ISSN   2306-5354. PMC   8698517 . PMID   34940358.
  16. 1 2 Li, Jianyu; Mooney, David J. (2016-10-18). "Designing hydrogels for controlled drug delivery". Nature Reviews Materials. 1 (12): 16071. Bibcode:2016NatRM...116071L. doi:10.1038/natrevmats.2016.71. ISSN   2058-8437. PMC   5898614 . PMID   29657852.
  17. ↑ Yang, Wan-Wan; Pierstorff, Erik (February 2012). "Reservoir-Based Polymer Drug Delivery Systems". SLAS Technology. 17 (1): 50–58. doi: 10.1177/2211068211428189 . PMID   22357608. S2CID   44557959.
  18. 1 2 3 Diaz-Rodriguez, Patricia; Sánchez, Mirian; Landin, Mariana (2018-12-13). "Drug-Loaded Biomimetic Ceramics for Tissue Engineering". Pharmaceutics. 10 (4): 272. doi: 10.3390/pharmaceutics10040272 . ISSN   1999-4923. PMC   6321415 . PMID   30551594.
  19. 1 2 Nilawar, Sagar; Uddin, Mohammad; Chatterjee, Kaushik (2021). "Surface engineering of biodegradable implants: emerging trends in bioactive ceramic coatings and mechanical treatments". Materials Advances. 2 (24): 7820–7841. doi: 10.1039/D1MA00733E . ISSN   2633-5409. S2CID   242035715. Archived from the original on 2024-03-16. Retrieved 2023-04-19.
  20. ↑ Singh, Maninder; Gill, Amoljit Singh; Deol, Parneet Kaur; Agrawal, Anupam; Sidhu, Sarabjeet Singh (2022-08-28). "Drug eluting titanium implants for localised drug delivery" . Journal of Materials Research. 37 (16): 2491–2511. Bibcode:2022JMatR..37.2491S. doi:10.1557/s43578-022-00609-y. ISSN   0884-2914. S2CID   249326879. Archived from the original on 2024-03-16. Retrieved 2023-04-19.
  21. 1 2 Brudno, Yevgeny; Silva, Eduardo A.; Kearney, Cathal J.; Lewin, Sarah A.; Miller, Alex; Martinick, Kathleen D.; Aizenberg, Michael; Mooney, David J. (2014-09-02). "Refilling drug delivery depots through the blood". Proceedings of the National Academy of Sciences. 111 (35): 12722–12727. Bibcode:2014PNAS..11112722B. doi: 10.1073/pnas.1413027111 . ISSN   0027-8424. PMC   4156738 . PMID   25139997.
  22. ↑ Anderson, James M.; Rodriguez, Analiz; Chang, David T. (April 2008). "Foreign body reaction to biomaterials". Seminars in Immunology. 20 (2): 86–100. doi:10.1016/j.smim.2007.11.004. PMC   2327202 . PMID   18162407.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.