Artificial bone

Last updated
Flexible hydrogel-HA composite, which has a mineral-to-organic matrix ratio approximating that of human bone Hydrogel-HA.jpg
Flexible hydrogel-HA composite, which has a mineral-to-organic matrix ratio approximating that of human bone

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. [1]

Contents

Bone fracture, which is a complete or partial break in the bone, is a very common condition that has more than three million US cases per year. [2] Human bones have the ability to regenerate themselves by cycle of bone resorption and bone formation. The cell responsible for bone resorption is osteoclast, while the cell responsible for bone formation is osteoblast. That being said, the human body can regenerate fractured bone. However, if damage to bone is caused by a disease or severe injury, it becomes difficult for the body to repair itself. When the human body is unable to regenerate the lost bone tissue, surgeons come in and replace the missing bone using autografts, allografts, and synthetic grafts (artificial bone). When comparing artificial bone to autograft and allograft, it is less invasive and more biocompatible since it avoids the risk of unknown viral infections. [3]

The use of solid freeform fabrication in design of composite scaffolds The use of Solid Freeform Fabrication in design of composite scaffolds.png
The use of solid freeform fabrication in design of composite scaffolds

When designing implanted biomaterials, key criteria are biocompatibility, osteoconductivity, high porosity and biomechanics compatibility. Artificial bone was initially made of materials like metals and solid ceramics, which are strong enough to sustain the loading in bone. However, the rigidity of those materials created an enormous burden on patients and was not consistent with the criteria for implanting biomaterials. Artificial bones made of metal and ceramic tend to do poorly in terms of biocompatibility since it is difficult to blend into bone tissues. [4] Thus, to better help those in need to live a more comfortable life, engineers have been developing new techniques to produce and design better artificial bone structure and material.

The two major components of bone are hydroxyapatite [Ca10(PO4)6(OH)2], and collagen fibers. Hydroxyapatite, which is one of the most stable forms of calcium phosphate, makes up about 60 to 65 percent of the bone. [5] The rest of the bone is composed of materials including chondroitin sulfate, keratan sulfate and lipid. [5] Increased research and knowledge regarding the organization, structure of properties of collagen and hydroxyapatite have led to many developments in collagen-based scaffolds in bone tissue engineering. The structure of hydroxyapatite is very similar to that of the original bone, and collagen can act as molecular cables and further improve the biocompatibility of the implant. [6]

Overview

Demographics of bone injury

In the United States, more than 6.5 million bone defects and more than 3 million facial injury cases have been reported each year. More than 2.2 million bone graft procedures are performed worldwide per year. The common causes for bone graft are tumor resection, congenital malformation, trauma, fractures, surgery, osteoporosis, and arthritis. [7] According to the National Ambulatory Medical Care Survey (NAMCS), in 2010, there were approximately 63 million visits to the orthopedic surgery department and about 3.5 million visits for fractures in the emergency departments in the U.S. Among the 6.5 million bone fracture or defect cases, approximately 887,679 people were hospitalized. [8]

Structure of chitin Structure of Chitin.png
Structure of chitin

Current areas of bone grafting (types of bones, composites)

Research on material types in bone grafting has been traditionally centered on producing composites of organic polysaccharides (chitin, chitosan, alginate) and minerals (hydroxyapatite). Alginate scaffolds, composed of cross-linked calcium ions, are actively being explored in the regeneration of skin, liver, and bone. [9] Alginate's ability to scaffold and makes it a novel polysaccharide. Even though many minerals can be adapted for bone composition, hydroxyapatite remains the dominant material, as its strength and the known Jager-Fratzl model of human bone provide a pre-existing framework for spacing and fabrication.

Material types

Preparation of chitin and chitosan from marine crustaceans Preparation of chitin and chitosan from marine crustaceans.png
Preparation of chitin and chitosan from marine crustaceans

Materials suited for use in artificial bones need to be biocompatible, osteoconductive, and mechanically strong. [5] Hydroxyapatite is often used in artificial bone studies because it has the biocompatibility and osteoconductivity required for an effective, long-lasting bone implant, but is quite brittle, [5] and further exhibits a dissolution rate of about 10 wt% per year, which is significantly slower than the growth rate of newly formed bone, necessitating measures to enhance its dissolution rate. [10] For applications that require a material with better toughness, nanostructured artificial nacre may be used due to its high tensile strength and Young's modulus. [11] In many cases, using one type of material limits the capabilities of an artificial bone implant, so composites are utilized. Implants composed of chitosan and hydroxyapatite take advantage of chitosan's biocompatibility and its ability to be molded into complex porous shapes as well as hydroxyapatite's osteoconductivity to create a composite that features all three traits. [5] Other composites suitable for use in artificial bone are those using alginate, a biopolymer known for its scaffold-forming properties. Uses for alginate in composites include chitosan composites for bone tissue repair, bioglass composites for repairing or replacing defective or diseased bone, or ceramic-collagen composites for bone regeneration. [9] The material used in an artificial bone implant ultimately depends on the type of implant being created and its use.

3D printing of artificial bones

3D printing is becoming an efficient way to produce artificial bones. First, a bone model is created by means of reconstruction of CAT scan images obtained from the patient. Then the artificial bone materials are used as "filament" for 3D printing. According to the resolution grafts, the 3D bone model would be divided into some layers. The printer would print a layer, then next one upon the last, and finally producing an artificial bone. Most of recently studies show hydroxyapatite (HA) nanocrystals are ideal material for 3D printed artificial bones. HA nanocrystals are synthesized by wet synthesis using diammonium phosphate and calcium chloride as phosphorus and calcium precursors, respectively. [12] Furthermore, polycaprolactone (PCL) can also be used for 3D printing producing of artificial bone in some research reports. Compared to repairing damaged bones, 3D printing technique could produce implants which meets personalized repair needs. On the other hand, 3D printing techniques produce implants with few adverse effects on patients. Host cells of varying classifications, such as lymphocytes and erythrocytes, display minimal immunological response to artificial grafts. [13]

Advantages

Material properties

Effective bone substitute materials should exhibit good mechanical strength along with adequate bioactivity. Bioactivity, which is often gauged in terms of dissolution rates and the formation of a mineral layer on the implant surface in-vivo, can be enhanced in biomaterials, in particular hydroxyapatite, by modifying the composition and structure by doping. [10] As an alternative to hydroxyaptatite systems, Chitosan composites have been thoroughly studied as one material to use for artificial bone. [5] Chitosan by itself can be easily modified into complex shapes that include porous structures, making it suitable for cell growth and osteoconduction. [5] In addition, chitosan scaffolds are biocompatible and biodegradable, but have low toughness, and the material itself is not osteoconductive. [5] Hydroxyapatite, on the other hand, features excellent biocompatibility but is hindered by its brittle nature. [14] When implemented with hydroxyapatite as a composite, both the toughness and osteoconductivity significantly improve, making the composite a viable option for material for artificial bone. [5] Chitosan can also be used with carbon nanotubes, which have a high Young's modulus (1.0–1.8 TPa), tensile strength (30–200 GPa), elongation at break (10–30%), and aspect ratio (>1,000). [5] Carbon nanotubes are very small in size, chemically and structurally stable, and bioactive. [5] The composite formed by carbon nanotubes and chitosan greatly improves the toughness of chitosan. [5] Nanostructured artificial nacre is another option for creating artificial bone. [11] Natural nacre is composed of an arrangement of organic and inorganic layers similar to brick and mortar. [9] This along with the ionic crosslinking of tightly folded molecules allow nacre to have high strength and toughness. [9] Artificial nacre that mimicked both the structure and the effect of the ionic bonds had a tensile strength similar to natural nacre as well as an ultimate Young's modulus similar to lamellar bone. [11] From a mechanical standpoint, this material would be a viable option for artificial bone.

Design consideration

Clinical results

Several aspects of any artificial bone design must be considered before implementing the design into a patient. Artificial bone implants that are an ill fit inside a patient due to events such as leaving the recipient bone unfixed can cause redness and swelling at the recipient region. [3] Ill fit implants may also be caused by sintering, which can cause dimensional contraction of an implant by up to 27%. [15] Osteoconductivity is another important consideration for artificial bone design. Sintered materials increase the crystallinity of calcium phosphate in certain artificial bones, which leads to poor resorption by osteoclasts and compromised biodegradability. [15] One study avoided this by creating inkjet-printed, custom-made artificial bones that utilized α-tricalcium phosphate (TCP), a material that converts to hydroxyapatite and solidifies the implant without the use of sintering. [15] In addition, α-TCP is biocompatible and helps form new bone, which is better for patients in the long term. [3] Artificial bone designs must be biocompatible, have osteoconductivity, and last for long periods of time inside a patient in order to be a viable solution compared to autologous and allogeneic bone implants.

Challenges

Surface properties

Artificial grafts maintain comparable compressive strength, but occasionally lack similarity to human bone in response to lateral or frictional forces. [16] In particular, the topography of artificial bone is inaccurate compared to its natural counterpart. In Grant et al., artificial bone grafts produced by fused deposition had on average a 20% lower coefficient of friction compared to real bone. [16] While CT scans and subsequent bone models are highly indicative of real bone for internal composition, the final product relies on the resolution of the printer. In cases where printer defects occur, the most likely issue is a decrease in compressive strength due to unintentional voids. [15] After implantation, decreased cellular proliferation and differentiation is evident as patients increase with age. This prolongs the integration of grafts and hinders the formation of bone tissue. In animal models, the incorporation of allografts causes teratoma formation. Whether or not the probability of this event is significantly increased remains to be seen. [2] Thus, scaffolding with other biological agents is necessary to mimic the framework of the body. Type I collagen, which constitutes a significant portion of the organic mass of bone, is a frequently used scaffolding agent. Alternatively, the polymer chitosan possesses similar biological response, namely the promotion of osteogenesis in vivo. [2]

Fabrication limitations

More modern fabrication techniques include inkjet printing. [17] In one study, a 3D inkjet printer produced autograft implants for the lower jaw of 10 patients. The hydroxyapatite implant was produced from tricalcium phosphate powder which hardened after hydration. [17] The surgical procedure was conducted for both aesthetic and function. All patients indicated satisfaction with the bone product. In another study, which examined replicate goat femurs, hydroxyapatite nanocrystals were produced and mixed on-site before loading a 3D printer. The study noted a slight decrease in compressive strength of the femurs, which could be attributed to imperfect printing and an increased ratio of cancellous bone. In general, 3D printing techniques produce implants with few adverse effects in patients. Host cells of varying classifications, such as lymphocytes and erythrocytes, displayed minimal immunological response to artificial grafts. [2] Only in the case of improper sterilization or previous predisposition to infection did any significant complications occur. The speed of printing is the primary rate-limiting step in artificial bone production. Depending on the type of bone implant, printing time can range from an hour to several. [15] As printers produce higher resolution grafts, the duration of printing increases proportionally.

Biological response

Research on artificial bone materials has revealed that bioactive and resorbable silicate glasses (bioglass), glass-ceramics, and calcium phosphates exhibit mechanical properties that are similar to human bone. [18] Similar mechanical properties do not assure biocompatibility. The body's biological response to those materials depends on many parameters including chemical composition, topography, porosity, and grain size. [18] If the material is metal, there is a risk of corrosion and infection. If the material is ceramic, it is difficult to form the desired shape, and bone can't reabsorb or replace it due to its high crystallinity. [3] Hydroxyapatite, on the other hand, has shown excellent properties in supporting the adhesion, differentiation, and proliferation of osteogenesis cell since it is both thermodynamically stable and bioactive. [18] Artificial bones using hydroxyapatite combine with collagen tissue helps to form new bones in pores, and have a strong affinity to biological tissues while maintaining uniformity with adjacent bone tissue. [3] Despite its excellent performance in interacting with bone tissue, hydroxyapatite has the same problem as ceramic in reabsorption due to its high crystallinity. Since hydroxyapatite is processed at a high temperature, it is unlikely that it will remain in a stable state. [3]

Related Research Articles

<span class="mw-page-title-main">Biopolymer</span> Polymer produced by a living organism

Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers, suberin and lignin, cutin and cutan, melanin, and polyhydroxyalkanoates (PHAs).

<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">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">Bioactive glass</span> Surface reactive glass-ceramic biomaterial

Bioactive glasses are a group of surface reactive glass-ceramic biomaterials and include the original bioactive glass, Bioglass. The biocompatibility and bioactivity of these glasses has led them to be used as implant devices in the human body to repair and replace diseased or damaged bones. Most bioactive glasses are silicate-based glasses that are degradable in body fluids and can act as a vehicle for delivering ions beneficial for healing. Bioactive glass is differentiated from other synthetic bone grafting biomaterials, in that it is the only one with anti-infective and angiogenic properties.

<span class="mw-page-title-main">Bone grafting</span> Bone transplant

Bone grafting is a surgical procedure that replaces missing bone in order to repair bone fractures that are extremely complex, pose a significant health risk to the patient, or fail to heal properly. Some small or acute fractures can be cured without bone grafting, but the risk is greater for large fractures like compound fractures.

<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">Nanofiber</span> Natural or synthetic fibers with diameters in the nanometer range

Nanofibers are fibers with diameters in the nanometer range. Nanofibers can be generated from different polymers and hence have different physical properties and application potentials. Examples of natural polymers include collagen, cellulose, silk fibroin, keratin, gelatin and polysaccharides such as chitosan and alginate. Examples of synthetic polymers include poly(lactic acid) (PLA), polycaprolactone (PCL), polyurethane (PU), poly(lactic-co-glycolic acid) (PLGA), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(ethylene-co-vinylacetate) (PEVA). Polymer chains are connected via covalent bonds. The diameters of nanofibers depend on the type of polymer used and the method of production. All polymer nanofibers are unique for their large surface area-to-volume ratio, high porosity, appreciable mechanical strength, and flexibility in functionalization compared to their microfiber counterparts.

<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.

A nerve guidance conduit is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical treatments for nerve injuries. When direct suturing of the two stumps of a severed nerve cannot be accomplished without tension, the standard clinical treatment for peripheral nerve injuries is autologous nerve grafting. Due to the limited availability of donor tissue and functional recovery in autologous nerve grafting, neural tissue engineering research has focused on the development of bioartificial nerve guidance conduits as an alternative treatment, especially for large defects. Similar techniques are also being explored for nerve repair in the spinal cord but nerve regeneration in the central nervous system poses a greater challenge because its axons do not regenerate appreciably in their native environment.

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">Bioceramic</span> Type of ceramic materials that are biocompatible

Bioceramics and bioglasses are ceramic materials that are biocompatible. Bioceramics are an important subset of biomaterials. Bioceramics range in biocompatibility from the ceramic oxides, which are inert in the body, to the other extreme of resorbable materials, which are eventually replaced by the body after they have assisted repair. Bioceramics are used in many types of medical procedures. Bioceramics are typically used as rigid materials in surgical implants, though some bioceramics are flexible. The ceramic materials used are not the same as porcelain type ceramic materials. Rather, bioceramics are closely related to either the body's own materials or are extremely durable metal oxides.

Socket preservation or alveolar ridge preservation is a procedure to reduce bone loss after tooth extraction. After tooth extraction, the jaw bone has a natural tendency to become narrow, and lose its original shape because the bone quickly resorbs, resulting in 30–60% loss in bone volume in the first six months. Bone loss, can compromise the ability to place a dental implant, or its aesthetics and functional ability.

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.

<span class="mw-page-title-main">Cell encapsulation</span>

Cell encapsulation is a possible solution to graft rejection in tissue engineering applications. Cell microencapsulation technology involves immobilization of cells within a polymeric semi-permeable membrane. It permits the bidirectional diffusion of molecules such as the influx of oxygen, nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products and therapeutic proteins. At the same time, the semi-permeable nature of the membrane prevents immune cells and antibodies from destroying the encapsulated cells, regarding them as foreign invaders.

<span class="mw-page-title-main">Surface modification of biomaterials with proteins</span>

Biomaterials are materials that are used in contact with biological systems. Biocompatibility and applicability of surface modification with current uses of metallic, polymeric and ceramic biomaterials allow alteration of properties to enhance performance in a biological environment while retaining bulk properties of the desired device.

Materials that are used for biomedical or clinical applications are known as biomaterials. The following article deals with fifth generation biomaterials that are used for bone structure replacement. For any material to be classified for biomedical applications, three requirements must be met. The first requirement is that the material must be biocompatible; it means that the organism should not treat it as a foreign object. Secondly, the material should be biodegradable ; the material should harmlessly degrade or dissolve in the body of the organism to allow it to resume natural functioning. Thirdly, the material should be mechanically sound; for the replacement of load-bearing structures, the material should possess equivalent or greater mechanical stability to ensure high reliability of the graft.

Bio-inks are materials used to produce engineered/artificial live tissue using 3D printing. These inks are mostly composed of the cells that are being used, but are often used in tandem with additional materials that envelope the cells. The combination of cells and usually biopolymer gels are defined as a bio-ink. They must meet certain characteristics, including such as rheological, mechanical, biofunctional and biocompatibility properties, among others. Using bio-inks provides a high reproducibility and precise control over the fabricated constructs in an automated manner. These inks are considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM).

Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface i.e. the bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.

Artificial ligaments are devices used to replace damaged ligaments. Today, the most common use of artificial ligaments is in anterior cruciate ligament reconstruction. Although autotransplantation remains the most common method of ligament reconstruction, numerous materials and structures were developed to optimize the artificial ligament since its creation in the World War I era. Many modern artificial ligaments are made of synthetic polymers, such as polyethylene terephthalate. Various coatings have been added to improve the biocompatibility of the synthetic polymers. Early artificial ligaments developed in the 1980s were ineffective due to material deterioration. Currently, the Ligament Advanced Reinforcement System (LARS) artificial ligament has been utilized extensively in clinical applications. Tissue engineering is a growing area of research which aims to regenerate and restore ligament function.

Bioactive glass S53P4 (BAG-S53P4) is a biomaterial consisting of sodium, silicate, calcium and phosphate. S53P4 is osteoconductive and also osteoproductive in the promotion, migration, replication and differentiation of osteogenic cells and their matrix production. In other words, it facilitates bone formation and regeneration (osteostimulation). S53P4 has been proven to naturally inhibit the bacterial growth of up to 50 clinically relevant bacteria strains.

References

  1. ↑ "ARTIFICIAL BONE GRAFTS: PRO OSTEON". Arthroscopy.com. Archived from the original on 2013-04-04. Retrieved 2013-11-16.
  2. 1 2 3 4 Kashte, Shivaji; Jaiswal, Amit Kumar; Kadam, Sachin (2017). "Shivaji Kashte, Amit Kumar Jaiswal, Sachin Kadam. (2017). Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges". Tissue Engineering and Regenerative Medicine. 14 (1): 1–14. doi:10.1007/s13770-016-0001-6. PMC   6171575 . PMID   30603457.
  3. 1 2 3 4 5 6 Saijo, Hideto; Fujihara, Yuko; Kanno, Yuki; Hoshi, Kazuto; Hikita, Atsuhiko; Chung, Ung-il; Takato, Tsuyoshi (2016). "Saijo, H., Fujihara Y., Kanno Y., Hoshi K., Hikita A., Chung U., Takato T. (2016). Clinical Experience of full custom-made artificial bones for the maxillofacial region". Regenerative Therapy. 5: 72–78. doi:10.1016/j.reth.2016.08.004. PMC   6581837 . PMID   31245504.
  4. ↑ "Creating Artificial Bones for Faster Bone Regeneration". Tokyo Institute of Technology. Retrieved 2018-04-20.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 Venkatesan, Jayachandran; Kim, Se-Kwon (2010). "Venkatesan, J., & Kim, S.-K. (2010). Chitosan Composites for Bone Tissue Engineering—An Overview". Marine Drugs. 8 (8): 2252–2266. doi: 10.3390/md8082252 . PMC   2953403 . PMID   20948907.
  6. ↑ Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca (2012). "Ferreira, A. M., Gentile, P., Chiono, V., & Ciardelli, G. (2012). Collagen for bone tissue regeneration". Acta Biomaterialia. 8 (9): 3191–3200. doi:10.1016/j.actbio.2012.06.014. PMID   22705634.
  7. ↑ Kashte, Shivaji; Jaiswal, Amit Kumar; Kadam, Sachin (2017). "Shivaji Kashte, Amit Kumar Jaiswal, Sachin Kadam. (2017). Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges". Tissue Engineering and Regenerative Medicine. 14 (1): 1–14. doi:10.1007/s13770-016-0001-6. PMC   6171575 . PMID   30603457.
  8. ↑ "NAMCS: Factsheet-ORTHOPEDIC SURGERY". Centers for disease control and prevention. Retrieved 2018-04-20.
  9. 1 2 3 4 Venkatesan, Jayachandran; Bhatnagar, Ira; Manivasagan, Panchanathan; Kang, Kyong-Hwa; Kim, Se-Kwon (2015). "Venkatesan, J., Bhatnagar, I., Manivasagan, P., Kang, K., & Kim, S. (2015). Alginate composites for bone tissue engineering: A review". International Journal of Biological Macromolecules. 72: 269–281. doi:10.1016/j.ijbiomac.2014.07.008. PMID   25020082.
  10. 1 2 Zhu, H.; et al. (2018). "Nanostructural insights into the dissolution behavior of Sr-doped hydroxyapatite". Journal of the European Ceramic Society. 38 (16): 5554–5562. arXiv: 1910.10610 . doi:10.1016/j.jeurceramsoc.2018.07.056. S2CID   105932012.
  11. 1 2 3 Tang, Zhiyong; Kotov, Nicholas A.; Magonov, Sergei; Ozturk, Birol (2003). "Tang, Z., Kotov, N. A., Magonov, S., & Ozturk, B. (2003). Nanostructured artificial nacre". Nature Materials. 2 (6): 413–418. doi:10.1038/nmat906. PMID   12764359. S2CID   6192932.
  12. ↑ Fan, Chunquan; Li, Jiashun; Xu, Guohua; He, Hailong; Ye, Xiaojian; Chen, Yuyun; Sheng, Xiaohai; Fu, Jianwei; He, Dannong (2010). "Fan, C., Li, J., Xu, G., He, H., Ye, X., Chen, Y., Sheng, X., Fu, J., He, D. (2010). Facile fabrication of nano-hydroxyapatite/silk fibroin composite via a simplified coprecipitation route". Journal of Materials Science. 45 (21): 5814–5819. doi:10.1007/s10853-010-4656-4. S2CID   136591597.
  13. ↑ Kashte, Shivaji; Jaiswal, Amit Kumar; Kadam, Sachin (2017). "Shivaji Kashte, Amit Kumar Jaiswal, Sachin Kadam. (2017). Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges". Tissue Engineering and Regenerative Medicine. 14 (1): 1–14. doi:10.1007/s13770-016-0001-6. PMC   6171575 . PMID   30603457.
  14. ↑ Zhou, Hongjian; Lee, Jaebeom (2011). "Zhou, H., & Lee, J. (2011). Nanoscale hydroxyapatite particles for bone tissue engineering". Acta Biomaterialia. 7 (7): 2769–2781. doi:10.1016/j.actbio.2011.03.019. PMID   21440094.
  15. 1 2 3 4 5 Saijo, Hideto; Igawa, Kazuyo; Kanno, Yuki; Mori, Yoshiyuki; Kondo, Kayoko; Shimizu, Koutaro; Suzuki, Shigeki; Chikazu, Daichi; Iino, Mitsuki; Anzai, Masahiro; Sasaki, Nobuo; Chung, Ung-il; Takato, Tsuyoshi (2009). "Saijo H, Igawa K, Kanno Y, Mori Y, Kondo K, Shimizu K, Suzuki S, Chikazu D, Iino M, Anzai M, Sasaki N, Chung UI, Takato T. (2009). Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology". Journal of Artificial Organs. 12 (3): 200–205. doi:10.1007/s10047-009-0462-7. PMID   19894095. S2CID   35626675.
  16. 1 2 Grant, J.A.; Bishop, N.E.; Götzen, N.; Sprecher, C.; Honl, M.; Morlock, M.M. (2007). "Grant, J., Bishop, N., Götzen, N., Sprecher, C., Honl, M., & Morlock, M. (2007). Artificial composite bone as a model of human trabecular bone: The implant-bone interface". Journal of Biomechanics. 40 (5): 1158–1164. doi:10.1016/j.jbiomech.2006.04.007. PMID   16806236.
  17. 1 2 Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong (2014). "Xu, N., Ye, X., Wei, D., Zhong, J., Chen, Y., Xu, G., & He, D. (2014). 3D Artificial Bones for Bone Repair Prepared by Computed Tomography-Guided Fused Deposition Modeling for Bone Repair". ACS Applied Materials & Interfaces. 6 (17): 14952–14963. doi:10.1021/am502716t. PMID   25133309.
  18. 1 2 3 Hoppe, Alexander; Güldal, Nusret S.; Boccaccini, Aldo R. (2011). "Hoppe, A., Güldal, N. S., & Boccaccini, A. R. (2011).A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics". Biomaterials. 32 (11): 2757–2774. doi:10.1016/j.biomaterials.2011.01.004. PMID   21292319.
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.