The basic method of bone tissue engineering is to use scaffold material as a carrier, and plant cells cultured in vitro on it to induce their growth and differentiation, and finally form new bone. It is not difficult to see that tissue engineering materials play a crucial role in the whole process.
From the perspective of bearing capacity, bone tissue engineering materials need to match the mechanical properties of bones, and have certain mechanical strength and toughness, so as to provide good support while avoiding stress obstruction. From the perspective of biocompatibility, the ideal bone tissue engineering material must have good biocompatibility, will not cause all kinds of rejection reactions in the human body, and have a certain porosity and good surface activity, which is conducive to cell adhesion, nutrient entry and blood vessel growth. In addition, it is necessary to ensure that the material implanted in the human body is degradable, the degradation rate needs to match the rate of new tissue regeneration, and the degradation products are non-toxic.
At present, there are a variety of materials used in bone tissue engineering, in general, they can be divided into inorganic non-metallic materials, metal materials, organic polymer materials, composite materials, etc.
1. Inorganic non-metallic materials
As far as the current research is concerned, the most widely used inorganic non-metallic materials in the field of bone tissue engineering are bioactive ceramics, also known as biodegradable ceramics, which have good biocompatibility. Bioactive ceramics can be divided into dense and porous types according to their structure.
Commonly used bioactive ceramics include hydroxyapatite (HA), tricalcium phosphate (β-TCP), silicate bioactive ceramics, etc.
1. Hydroxyapatite (HA):
It is a kind of bioactive material, the main components are calcium and phosphorus, similar to the composition of inorganic salt components of human bone in the natural state, and the structure is also extremely similar, this porous structure can significantly promote the large-scale adhesion, proliferation and differentiation of bone cells, after its implantation in the human body, it has a strong ability to bond with bone tissue, and is a good bone tissue defect repair material, which solves the problem of rejection of the possible existence of autologous bone tissue and allogeneic bone tissue with less source of autologous bone tissue, so it is widely used in the field of hard tissue repair and replacement.
Figure 1 Hydroxyapatite
2. Tricalcium phosphate (β-TCP):
According to its structure, it can be divided into high-temperature phase α-TCP and low-temperature phase β-TCP, the former has a greater degradation rate than the latter, and β-TCP is mainly used in bone defect repair. The chemical composition of β-TCP is non-cytotoxic, can bear the normal load of the implant site after implantation, meets the mechanical property requirements of human hard tissues, and has good biocompatibility, bone guidance and degradability, and is rapidly degraded in the physiological environment after implantation, and the degradation products Ca and P can enter the living circulatory system (Fig. 2).
Fig.2 Tricalcium phosphate bone scaffold
3. Silicate bioactive ceramics:
Compared with hydroxyapatite and tricalcium phosphate, the research of silicate bioactive ceramics started late. In recent years, silicate bioactive ceramics have attracted more and more attention from researchers, mainly because silicate bioactive ceramics can release bioactive ions such as silicon (Si) ions. From the perspective of elements, silicon is an important trace element in human tissues, and the quality of bone and its absorption level are directly related, especially in the stage of young bone development, silicon will be enriched in the new bone calcification area, promoting the early calcification of bone tissue. Therefore, if silicate bioactive ceramics are implanted into the human body as bone tissue engineering scaffold materials, they can significantly promote the proliferation and differentiation of bone tissue cells and bone tissue repair.
II. Descendable metal materials
Metal materials have high mechanical strength, good elasticity, plasticity and other comprehensive properties, and have been used as orthopedic implants for many years. At present, widely used metal materials include stainless steel, titanium alloy, cobalt alloy, etc., which are all permanent implants, which are easy to cause complications such as stress blocking, metal ion release, and chronic inflammation after long-term implantation in the human body.
In recent years, the research and development of magnesium-based biomedical materials has attracted close attention. Compared with other commonly used metal materials, magnesium mainly has the following advantages:
(1) Magnesium is the fourth most abundant cation in the human body, second only to calcium, potassium and sodium, and is also an essential nutrient element in the human body, which can activate a variety of enzymes and stabilize the structure of DNA and RNA, which has an important impact on the function of nerves, muscles, bones and hearts.
(2) It has good biocompatibility and biodegradability, and studies have shown that during the degradation process, the daily release of magnesium is only at the milligram level, which is far lower than the daily magnesium intake of the human body;
(3) Good mechanical compatibility, the density of magnesium is 1.74g/cm3, which is the closest to the density of human bone among all metal materials used in bone tissue engineering, which can effectively reduce the stress shielding effect and promote the growth of new bone.
Fig.3. Porous metals
3. Organic polymer materials
1. Natural polymer materials
Including collagen, chitosan, fibrin, alginate, etc., these natural polymer materials have good biocompatibility and have cell recognition signals, which are conducive to cell adhesion, proliferation and differentiation.
(1) Collagen: It is a natural protein, accounting for more than 30% of the total protein in the human body, and is also one of the main components of bone tissue, with the highest content in the extracellular matrix, which can provide an indispensable three-dimensional structure for calcified tissue structure. Collagen itself is non-toxic, can be recognized and labeled by cellular enzymes, in which cells can well adhesion, proliferation and differentiation, play an osteogenic role, its superior biocompatibility and biodegradability make it widely used in bone tissue engineering scaffold materials, and its degradation products can be absorbed by the body.
(2) Chitosan: It has good biocompatibility and biodegradability, no immune response to the human body and tissues, and has a certain effect of anti-inflammatory and wound healing, and can be made into a three-dimensional porous scaffold with certain mechanical strength and suitable for different defect parts, which is an ideal extracellular matrix material.
(3) Fibrin: Like collagen, fibrin is also a natural component of the extracellular matrix. Fibrin gel is a three-dimensional network structure formed by the cross-linking of peptide bonds by fibrin monomers under the action of thrombin and Ca2+, which is plastic, adhesive and degradable. In addition, because fibrin is derived from its own blood, the prepared fibrin gel has no immunogenicity problems and is an ideal extracellular matrix material.
(4) Alginate: It is a polysaccharide polymer isolated from seaweed, which is composed of dexmannitol uronic acid and L-guloic acid, which can provide a good three-dimensional growth environment for cells and maintain a good morphology, and its degradation products have no side effects on the human body, therefore, alginate is often used as a carrier for cell culture in bone tissue culture to synthesize polymer materials (Fig. 4).
Fig.4. Alginate powder
2. Artificial synthetic polymer materials
It has good degradable absorption, and at the same time, the composition, structural form, mechanical properties, and degradation rate of the material can be pre-designed and controlled to a certain extent to meet different needs, and can be standardized for large-scale production, so it is a scaffold material with more research and wide application in tissue engineering materials.
The main synthetic polymer materials commonly used in bone tissue engineering include polylactic acid (PLA), polyglycolic acid (PGA) and lactic acid/glycolic acid copolymer (PLGA), as well as polycaprolactone (PCL) and polyhydroxybutyrate (PHB).
(1) Polylactic acid (PLA): There are three isomers, namely L-polylactic acid (PLLA), D-based polylactic acid (PDLA), and racemic polylactic acid (PDLLA), of which PDLLA is an amorphous structure, with flexible mechanical properties and a relatively short degradation time, about 6~12 months.
(2) Polyglycolic acid (PGA): It has only moderate initial mechanical properties, and its strength decays quickly during degradation, but it has good biocompatibility and can promote the adhesion and proliferation, induction and differentiation of osteoblasts.
(3) Lactic acid/glycolic acid copolymer (PLGA): It is a polymer formed by the copolymerization of lactic acid and glycolic acid monomer, which has good biocompatibility and biodegradability, and can be made into porous scaffolds, and provide initial strength, regulate and control its degradation rate, so that it matches the growth rate of new bone, and then let the stress gradually transfer from the material to the new bone tissue.
(4) Polycaprolactone (PCL): It has stable chemical properties and good mechanical properties, is non-toxic to the human body, easy to process and mold, and has the characteristics of inducing tissue regeneration, regulating cell growth and functional differentiation after chemical modification.
Fig.5 PCL material
(5) Polyhydroxybutyrate (PHB): It is non-toxic and immunogenic to the human body, and has good biocompatibility and degradability, which is conducive to cell adhesion and differentiation, making it a new tissue engineering material. Its unique piezoelectric effect that stimulates the formation of new bone makes it ideal as an internal fixation material for fractures.
Fourth, composite materials
In today's rapid development of bone tissue engineering, the application of single materials is more and more limited due to its own characteristics, and it is difficult to meet the multiple requirements of bone tissue engineering for materials: for simple inorganic materials, although they have good biocompatibility and are easy to induce the generation of new bone, they are brittle, brittle, and brittle. For simple organic polymer materials, although they have good degradable absorption, their structure and function are quite different from the real bone tissue of the human body, and there are shortcomings such as poor mechanical properties, and the accumulation of degradation products makes the surrounding environment acidic, which is not conducive to tissue healing.
To sum up, it is a research hotspot in the field of bone tissue engineering to compound several single materials through a certain method, give full play to the advantages of each single material, learn from each other's strengths and complement each other's weaknesses in performance, and optimize the combination, so as to improve the mechanical strength, degradation time, and biological activity of bone tissue engineering materials. For composite scaffolds, they can be divided into composite stents of the same kind of materials and composite stents of different materials.
For the composite scaffolds of the same materials, there are mainly natural polymer material composite scaffolds, synthetic polymer material composite scaffolds and inorganic material composite scaffolds, and for different kinds of material composite scaffolds, there are mainly natural polymer materials and inorganic materials composites, synthetic polymer materials and inorganic materials and metal matrix composites.
Among these composites, natural materials have shortcomings such as difficult to reproduce properties, difficult to produce in large quantities, and unable to maintain spatial configuration during in vivo hydrolysis; the bulk degradation characteristics of synthetic biopolymer materials will cause the scaffold to lose its structural integrity prematurely, and the accumulation of local degradation products will cause inflammatory reactions; and the composite between synthetic inorganic materials has the shortcomings of high brittleness, poor wettability, and poor degradation performance.
Cross-lamination can overcome the shortcomings of single-material scaffolds. Among them, the combination of inorganic non-metallic materials and organic polymer materials to develop porous composite materials with good biological activity and mechanical properties is one of the most promising materials in bone tissue engineering. Organic polymer materials can supplement the toughness of inorganic materials, so as to meet the standard of mechanical requirements, while inorganic materials can induce new bone formation, which plays a buffering role in the acidic environment after degradation of polymer materials in this process.
Fig.6. Polymer/inorganic composite scaffold
At the same time, some researchers have set their sights on metal-based crossover composites, seeking new types of degradable bone tissue engineering scaffolds. With the rapid development of tissue engineering, bone tissue engineering materials are also undergoing a transformation from single materials to composite materials, and the types of materials available for people to choose are becoming more and more diverse according to the different mechanical properties and biocompatibility requirements of different bone tissues, and they are constantly innovating.
However, there are still many unsolved problems in practical clinical application, especially the application research of new materials is becoming a new research focus. For example, the combination of polyetheretherketone (PEEK) and more advanced biomechanical design and additive manufacturing technology enables bone tissue repair to be customized for different groups of people and different tissues, so as to obtain better repair results.
bibliography
[1] Cui Yan, Yang Fan, Liu Jiahe, Li Chenzhi, Li Yancheng, Wu Mingjian, Li Zhenhao, Xiong Wanqi, Liu Baoyi.3D Research progress of printing porous tantalum internal structure and surface modification in bone tissue engineering[J].Biological Orthopedic Materials and Clinical Research,2024,21(01):65-70.
[2] Yang Jiajie, Liu Hefei, Shi Xiaojian, Shen Meihua, Qin Chao, Shen Lingjie, Shi Kaibing.3D Digital design and analysis of printed porous titanium scaffolds[J].Biological Orthopedic Materials and Clinical Research,2024,21(01):79-85+89.
[3] Liu Wei, Zhao Jingsheng, Wang Yilin, Li Suli.3D Optimal design of interbody fusion device for printing different bone densities[J].China Journal of Medical Devices,2024,48(01):20-25.
[4] Wu Yan, Wang Yudong, Liu Mengxing, Shi Dufang, Hu Nan, Feng Wei.Design, manufacturing and application of porous implants based on 3D printing process[J].China Journal of Medical Devices,2024,48(01):15-19.
[5] Fu Ruizhi, Jiang Xi, Li Yuan, Zhu Jinqing, Ma Chunbao.Application of titanium metal powder in 3D printing of orthopedic implants and its impact on 3D printing[J].China Medical Device Information,2024,30(01):18-21.
[6] Yang Yunxiao, Zhao Yu, Wang Minghai, Yang Zezheng, Wang Jinwu.3D Printing personalized cervical orthopedic brace can alleviate and treat early cervical spondylosis[J].Chinese Tissue Engineering Research,1-6.
[7] Chen Huiguo, Shao Rongxue, Ruan Liqi, Le Jun, Hu Jintao, Zhou Hui.3D Application of print-guided template in osteoporosis posterior lumbar fusion[J].Journal of Practical Orthopedics,2023,29(12):1057-1061.
[8] He Xijing, Pei Fuxing, Huang Weidong.3D Printing Orthopedic Therapeutics.People's Medical Publishing House.2021/09.ISBN: 9787117315616.
[9] Fu Xiaobing et al.Regenerative Medicine:Biomaterials and Tissue Regeneration.People's Medical Publishing House.2021/09/01.ISBN:9787117312844.
Disclaimer: This article comes from professional journals and books, edited and synthesized by Orthopedics Online, if it involves copyright issues, please contact us.