Foreword

The research and development level and industrialization scale of new materials have become an important indicator for measuring a country's economic development, scientific and technological progress and national defense strength. Accelerating the development of new materials has important strategic significance for promoting technological innovation and industrial upgrading.

Degradable medical polymer materials can be gradually degraded due to specific or non-specific breakage of molecular chains in the in vivo environment, and the degradation products can be absorbed by the human body or excreted through the metabolic process without causing secondary damage to human health. It has become a class of biomedical materials that have attracted much attention.

my country's "14th Five-Year Plan" and "Made in China 2025" have proposed to focus on the development of high-value medical devices such as fully degradable vascular stents.

Degradable medical materials have good compatibility with human tissues, can be absorbed or completely excreted by the human body after being degraded in the human body, will not accumulate in the internal tissues or organs of the human body, and have strong stability and easy processing. Because of its simplicity, it has broad development prospects in the medical field and has been used in tissue repair, implant intervention, drug delivery, wound healing, etc.

More and more studies have shown that the effective application of biodegradable polymer materials in complex in vivo environments, especially the final clinical translation of materials, still faces a series of key issues and challenges. In order to adapt to medical applications in different in vivo environments, degradable polymer materials are made into different types of materials or products such as micro-nano particles, gels, and implantable devices through self-assembly, chemical reactions, and molding processes.

Natural degradable medical materials

Natural degradable polymer biomaterials include proteins (collagen, fibrin, silk, etc.), polysaccharides (starch, alginate, chitin, hyaluronic acid derivatives, etc.), natural polyesters, etc. Although natural degradable medical materials have a similar structure to human tissues, they will have various adverse consequences in the process of interacting with the human body. Therefore, synthetic degradable medical biomaterials that can be designed and developed have greater application potential in the medical field.

Synthetic degradable medical materials

Synthetic degradable biomedical polymer materials can be degraded into small molecules or monomers under the action of acid, alkali or enzymes in the body, or metabolized into carbon dioxide and water, and degraded by themselves after implantation in the body. At present, the research on the synthesis of degradable biomedical polymer materials is mainly based on the properties of polymer materials to develop their applications in the medical field.

Aliphatic polyester has good biocompatibility and biodegradability, and is an important raw material for the synthesis of degradable polymer medical materials. Polyglycolic acid (PGA), polylactic acid (PLA), and polylactic-co-glycolic acid (PLGA) are the most commonly used biodegradable biomedical polymer materials in biological tissue engineering and 3D scaffolds.

Polyglycolic acid (PGA) has rapidly degraded hydrophilic properties and can be rapidly dissolved in the human body. In addition, due to its flexibility in material properties, PGA can be used in scaffold-based tissue engineering construction, as well as drug delivery and wound healing. , it has been demonstrated that PGA binds fibrin in the treatment of soft tissue wounds.

Polylactic acid (PLA) is another widely used degradable material in biomedicine. Although its structure is similar to PGA, its properties are quite different. Due to its good relatively long-term mechanical properties in the human body, it is a load-bearing material for orthopaedic fixation. At present, a variety of orthopedic products have been developed based on PLA, such as soft tissue fixation screws and phantom suture anchors. The development of polylactic acid-based degradable medical polymer materials is one of the most active research topics in recent years. Various medical device companies in my country continue to explore self-developed biodegradable material products. Absorbable coronary stents based on composite materials such as Lepu Medical NeoVas and Shandong Huaan Xinsorb have been approved by the State Food and Drug Administration in China.

Poly(lactic-co-glycolic acid) (PLGA) controls the degradation rate and retention time in the human body by adjusting the ratio of PGA and PLA, so PLGA is often used in combination with ceramic/bioactive materials to enhance the ability of bone regeneration. Experiments have proved that the implant of PLGA and alloy composite material has obvious antibacterial, osteoconductive, osteoinductive and other properties, which provides a new direction for orthopedic surgery.

Polycaprolactone (PCL) can be degraded by microorganisms, hydrolysis, enzymatic, etc. Compared with PLA, PGA, PLGA, the degradation rate is slow, so it is generally used for long-term implants and drug delivery. Studies have shown that PCL can be used for effective drug delivery and delivery, and research on micro- and nano-scale drug delivery systems with PCL as the core is still hot. Additionally, PCL-calcium phosphate scaffolds have been shown to be cytocompatible in vitro for tissue repair.

Polyurethane (PUR) is ideal for medical devices due to its toughness, durability, biocompatibility, and biostability, often used as heart valves, vascular grafts, catheters, and prostheses, among others. Combined with lysine diisocyanate, PUR enhances cell proliferation and adhesion and can be used to develop highly porous scaffolds.

Polyethylene glycol (PEG) has excellent gel properties and degradability, good biocompatibility, non-toxicity and low immunogenicity. In medical devices, PEG derivatives are mainly multi-armed structures. Due to their relatively large molecular weight, they can form hydrogels, which can be mainly used for surgical suturing and hemostasis, assisting tissue regeneration and wound healing. After spraying the PEG hydrogel to the wound site, the hydrogel rapidly solidified to prevent wound bleeding and infection, and degraded on its own after the wound healed. Meanwhile, spraying the PEG hydrogel onto the organ surface can effectively prevent the adhesion of internal organs during surgery.

Application of degradable medical materials

1. Coronary stent

From the perspective of the evolution of coronary stents, coronary stents have gone through four development stages: relay balloon expansion, bare stent drug-eluting stents (DES) and degradable stents. Compared with traditional permanent metal stents, degradable stents can effectively avoid short-term and long-term risks of permanent implants in the body, such as long-term inflammation, displacement and fracture risk caused by long-term stimulation of foreign bodies; it can also avoid MRI, Imaging tests such as CT have a persistent impact.

After the introduction of degradable stents in 2011, it is expected to solve the problem of permanent implantation and benefit patients significantly, and it has become the research and development direction of leading cardiovascular enterprises. In February 2019, the biodegradable stent (NeoVas) developed by Lepu Medical was officially approved by the State Drug Administration and was the first biodegradable stent approved for marketing in China. In June 2020, the world's first two patients with IBS implanted with iron-based degradable coronary stents completed a two-year follow-up in Fuwai Hospital, proving that iron-based stents can be safely degraded in the human body.

2. Vena Cava Filter

At present, the mainstream design in the domestic and foreign markets is the recyclable vena cava filter, but the recovery rate of the filter in actual clinical practice is low, and if the filter is not recovered and left in the patient's body for a long time, it will lead to many complications. The degradable vena cava filter has the functions of recycling and degradation conversion at the same time, which can be degraded and converted into a stent-like structure in the patient's body, without the need for secondary surgery, and at the same time reduce the long-term complication rate of long-term indwelling of the filter.

3. Oral Restorative Film

Oral repair membranes can be subdivided into collagen membranes, metal membranes, synthetic membranes and allogeneic periosteum according to the source of materials, and can be subdivided into absorbable membranes and non-absorbable membranes according to whether the materials can be degraded. Among them, the non-degradable membrane requires a second operation to remove, and the non-collagen absorbable membrane does not require a second operation, but has the side effect of inflammation caused by acidic degradation products. In comparison, degradable collagen membranes have the most comprehensive advantages.

At present, the mainstream biodegradable collagen-based oral prosthetic membranes use tissue engineering technology on calf skin, pig skin or pig intestinal mucosa, undergo strict and effective decellularization treatment, and fire extinguishing treatment of viruses and other pathogens, retaining the natural collagen fiber spatial structure. . The main component is collagen, and no external chemical cross-linking agent is added during the production process. It is a pure natural biological material and can be degraded in the body without the need for secondary surgery. The degradation products will not cause the body's immune response.

Suggestions on the development of degradable medical materials industry in China

The development of biomedical materials has become the "source of living water" for the innovation and development of medical devices in my country. The future development trend of the biodegradable medical materials industry will be to combine the function and technology of polymers for specific biomedical applications. The development of degradable medical materials should meet the development needs of the downstream medical device industry, develop a new generation of vascular stents, nerve repair catheters, artificial bone tissue repair materials and other products, and explore the artificial construction of valves, liver, kidney and other tissues and organoids, actively Promote the application of bio-3D printing technology.

The collaborative innovation of government, industry, academia and research is an important guarantee for the sustainable development of biomedical material technology and industry. It is necessary to establish more collaborative innovation platform systems for talent training and key technology research and development, so that the market, enterprises and scientific research institutes can better cooperate, accelerate the research and development, testing, production, and application of new products, and build a complete modern biomaterials science and industry innovation system . Domestic innovative biomedical materials and medical devices will be preferentially included in the scope of medical insurance, and the process of localization and substitution of high-end medical device products will be accelerated.