Key Inorganic Components of Bone Matrix Nanohydroxyapatite: Comparison
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Please note this is a comparison between Version 2 by Amina Yu and Version 1 by Adhisankar Vadivelmurugan.

Each cell type has a specific binding motif on the extracellular matrix, and these interaction spots are nanometers in size; therefore, the physical properties of a surface such as roughness and topography are generally designed in nanoscales. In vitro, osteoblast adhesion, proliferation and differentiation, and mineralization are enhanced for nanomaterials with grain sizes less than 100 nm. The adherence of osteoblasts on the surface covered with titanium nanoparticles is threefold that on the conventional titanium-particle-coated surface. It becomes clear that anchorage-dependent bone-forming cells on rough scaffold surfaces show higher attachment, proliferation, and differentiation efficiency.

  • interfaces
  • bone matrix
  • osseointegration

1. Introduction

Galindo et al. [24][1] reported that a new method accumulates nHAp on a polymer matrix to produce composites with better physical properties and higher biocompatibility and bioactivity. To establish new biomedical applications, the interfacial interactions between polymer and HAp in biofusion should be investigated. Simple coating techniques have been used to establish nHAp/polymer blending interfaces for in vitro studies of interfacial interactions between proteins and cells, which reveal better biocompatibility, mechanical properties, and biodegradability. The cells cultured with the spherical nHAp suspension show better cellular responses including adhesion, proliferation, and cell–matrix interactions, which implies that spherical nHAp particles are more useful than acicular (needle-like)-shaped particles. The studies demonstrate that nHAp with a particle size of 20 nm increases the viability and proliferation of bone marrow mesenchymal stem cells (BMSCs) and represses the growth of osteosarcoma cells. Nano-HAp particles with diameters of approximately 50 nm exhibit apoptotic action of the hepatoma cell line. Studies of interfacial interactions formed between biomolecules and nHAp were performed, and the distribution of these interactions by appropriate protein preadsorption was also summarized. In addition, compared with pure HAp, doping strontium in HAp can improve solubility and promote the differentiation and mineralization of osteoblast-like cells, therefore, Sr–HAp as a substrate for bone cell culture scaffolds have attracted increasing attention in recent years [25,26,27][2][3][4]. Moreover, some studies have proven that bioglass (BG) can lead to the formation of a hydroxycarbonate apatite layer on the surface when BG contacts with body fluid, which then enhances bone regeneration [28][5]. Rizwan et al. [29][6] reported a low-pressure spark plasma sintering (SPS) procedure to prepare HAp–bioglass (BG) composite scaffold materials with BG contents up to 30 wt.%. When compared with traditional sintering, the delicate processing of the SPS procedure with compaction pressure and sintering time provided HAp–BG composite scaffolds without inordinate reactions among constituents, which also prohibited the crystallization of the BG. Increasing the BG content not only strengthens the physical properties, such as the relative density, bulk density, and hardness, but also demonstrates the enhanced bioactivity of the composite samples in vitro.

2. Poly(ε-caprolactone)

In bone engineering applications, poly(ε-caprolactone) (PCL) can be classified among materials that enable biocompatibility with biodegradable polymers, as it is used to treat bone defects and has the effects of increasing bone ingrowth and regeneration [30,31][7][8]. Moreover, its good flexibility makes it an attractive candidate for accompanying tissue-guided regeneration (GTR) as a membrane for the treatment of periodontal diseases [32,33][9][10]. Nyberg et al. [34][11] reported the first successful 3D-printed composites with porous PCL mineral scaffolds and differentiated their relative capacities to drive osteoinduction in adipose-derived stem cells. Herein, the 3D-printing system PCL–Bio-Oss (BO) along with PCL–decellularized bone matrix (DCB) displayed more osteoinduction than the synthetic materials PCL–hydroxyapatite (HAp) or PCL–tricalcium phosphate (TCP). However, their results demonstrate that doping 3D-printed PCL scaffolds with DCB, BO, or synthetic particles provides different degrees of bone healing support in vivo.
Cho et al. [35][12] reported that the PCL–hydroxyapatite nanoparticle (nHAp) composite structure and the exposure of nHAp enhanced the mechanical properties as well as the bone-regeneration capability of the material-extrusion scaffold. In their study, a PCL–nHAp composite scaffold with a crystalline structure was assembled using a material extrusion method, indicating that mechanical properties were enhanced not only by the composition but also by the structure. Meanwhile, the mechanical properties and in vitro cell response were enhanced by increasing the weight ratio of the resolved nHAp. The electrospinning technique is a useful method to fabricate a mimic extracellular matrix (ECM) nanofibrous structure scaffold. The gelatin/PCL electrospun matrix surface coated with nHAp not only increased the roughness of the surface to enhance cell adhesion but also established a biomimetic environment to promote cell growth [36][13]. Naudot et al. [37][14] evaluated the efficiency of bone regeneration in a 3D cylindrical structure composite created from electrostatic template-excited deposition through the alternate deposition of electrospun PCL nanofibers, including electrosprayed hydroxyapatite nanoparticles (nHAp), to produce a honeycomb micropatterned substrate. They first established the cytocompatibility of this honeycomb PCL–nHAp scaffold in culture with BMSCs. The scaffold was then embedded (with or without seeded BMSCs) in a rat critical-sized calvarial defect model for 2 months. Microcomputed tomography was used every 2 weeks to observe new bone formation in situ. The images showed that the honeycomb PCL–nHAp scaffold was osteoconductive. In addition, the growth of the scaffold containing BMSCs was combined with remarkably greater bone volume during the 2-month experiment. Thus, if the biomimetic honeycomb PCL–nHAp scaffold can be loaded with patient MSCs, it might, therefore, have great potential in maxillofacial applications. Based on the Sr–HAp possessing elevated osteogenic potential relative to pure HAp, Tsai et al. [38][15] have produced PCL/Sr-substituted hydroxyapatite nanofibers (PCL/SrHANFs) with electrospinning to evaluate the behavior of osteoblasts. The results found that PCL/SrHANFs enhanced the expression level of osteogenic proteins, such as alkaline phosphatase (ALP), osteocalcin (OCN), and bone sialoprotein (BSP), compared to PCL membranes alone. Melt electrospinning writing (MEW) is a newly imminent 3D-printing technique to fabricate more advanced microfibril 3D scaffolds [39][16]. Wang et al. [40][17] united MEW with solution electrospinning (SE) technologies and successfully prepared PCL/gelatin micro/nano-fibril scaffolds. The mechanical strength of the scaffold was provided by the PCL microfibers and induced cell orientation, whereas the long-term hydrophilicity of the scaffold was increased by the inclusion of gelatin nanofibers and induced cell adhesion and proliferation. After 7 days of culture, their results showed that cells could be distributed throughout the whole multilayer dual-scale composite scaffold, which indicated that cells could migrate through the gaps between nanofibers. In contrast with conventional 3D scaffolds, the MEW composite scaffolds exhibited not only good mechanical properties in addition to cell orientation effects but also a cell-identified ECM-mimicking 3D microenvironment.

3. Poly(lactic-co-glycolic Acid), PLGA

PLGA has been used in several clinical applications and has been shown to be biocompatible, nontoxic, and noninflammatory [41,42][18][19] but rarely used in the orthopedics area owing to its low mechanical strength, ductile characteristics, and absence of osteogenic bioactivity [43][20]. Generally, the surface chemistry of PLGA does not entirely support cell adhesion for enhancing bone ingrowth and proliferation because of its hydrophobic nature [44][21]. Organic solvents are commonly used to fabricate polymer/ceramic composite scaffolds; however, they have the potential to destroy cells or tissues. In addition, composite scaffolds fabricated using conventional and traditional methods limit the exposure of ceramic on the scaffold surface. A novel fabrication technique was proposed to expose the ceramic on the surface of the scaffold to enhance the osteoconductivity and bioactivity of the scaffold. PLGA/nHAPF scaffolds were assembled through the gas spraying and particulate leaching (GF/PL) technique without the use of organic solvents [45][22]. Selective staining of ceramic particles showed that nHAp on the scaffold surface was more numerous on the GF/PL scaffold than on scaffolds prepared with traditional solvent casting and particulate leaching (SC/PL). In vivo evaluation was performed by embedding both scaffolds into critical-size defects in rat skulls for 8 weeks to observe bone regeneration. In defect areas, bone formation was more comprehensive on the GF/PL scaffolds than on the SC/PL scaffolds as examined with histological analyses and microcomputed tomography. Higher exposure of HA nanoparticles on the scaffold surface may be responsible for more bone formation on the GF/PL scaffolds than on the SC/PL scaffolds. Li et al. [46][23] utilized gelatin as the medium to coat nHA and chitosan on PLLA microspheres. Compared with noncoated PLLA microspheres, the greatest proliferation-promoting effect was observed with the nHA-coated microspheres, and the nHA/chitosan microcarriers enhanced osteogenic expression.
Wang et al. [47][24] established a biomimetic, ordered nanostructure on the surface of the interior pores of nHAP-coated PLGA scaffolds and studied the effects of the porosity of the PLGA/nHAP on cell behaviors. Both the viability and proliferation rates of cells implanted in the nHAP-coated PLGA scaffolds were greater than those in the PLGA scaffolds alone. In bone defect repairs, the radius defects had, after 12 weeks of implantation of nHAP-coated PLGA scaffolds, fully recovered with undoubtedly better bone formation than that seen with the group of PLGA scaffolds, as shown by X-ray, microcomputerized tomography, and histological experiments. Mao et al. [48][25] reported the assembly of poly(lactic acid)/ethyl cellulose/hydroxyapatite (PLA/EC/HAp) composite scaffolds for potential applications as weight-bearing bone replacements in tissue engineering. The mixed method used herein this study greatly expanded the mechanical properties more than the particulate leaching method. The results show that PLA/EC/HAp scaffolds at the 20 wt.% HAp loading level demonstrated excellent mechanical properties along with the desired porous structure. The porosity, contact angle, compressive yield strength, and percent of weight loss after 56 days met the physiological requirements regulating bone regeneration. These results suggested that the PLA/EC/HAp scaffolds assembled by combining several fabrication techniques such as high-concentration solvent casting, particulate leaching, and room-temperature compression molding have possible applications in bone tissue engineering.

4. Naturally Derived Materials

The degradation rate of chitosan mainly depends on the degree of crystallinity and acetylation [49][26]. Chemical alteration of the chitosan polymer significantly affects the degradation and solubility rate, and the biodegradation of a highly deacetylated form was observed over several months in vivo [50][27]. In brief, chitosan can be degraded by nontoxic products in vivo, so it has been commonly used in diverse biomedical applications. However, its application in tissue engineering is limited by poor hydrophilicity and cytocompatibility. Acevedo et al. [51][28] reported that they prepared a new gelatin–chitosan polymeric membrane that incorporated osteoconductive materials, nHAP, and titania nanoparticles. Modulation of the mechanical properties and the biodegradable rate of the nanocomposite membrane was completed with UV-radiation-induced cross-linking. The basic function of gelatin-based materials is to act as a physical barrier, but titania and hydroxyapatite nanoparticles, known as osteoconductive materials, endow the composite with osteogenic potential. The described material is a great alternative to other bone-regeneration membranes and has the potential to be used in oral/orthopedic applications.
Chitosan is often used in a gel form for application; for example, Wang et al. [52][29] combined nHAp and chitosan to fabricate a drug-containing hydrogel to investigate its efficiency to treat infected bone defects. Their results showed that the infection was eliminated, and the defects were restored faster than those in the control group. Abazar et al. [53][30] reported that electrospun nanofibrous scaffolds were assembled by applying HAp, polyvinyl alcohol (PVA), chitosan polymers, and platelet-rich plasma (PRP), a bioactive substance isolated from human blood. An in vitro study of scaffold osteoinductivity was performed via osteogenic differentiation of mesenchymal stem cells (MSCs), and an in vivo study of osteoconductivity was performed by implantation into a critical-sized rat calvarial defect. In vitro alkaline phosphatase activity, calcium content, and gene expression assays demonstrated that the scaffolds had good structures and good biocompatibility. The in vivo results showed that the defect was renovated to a good extent in animals implanted with PVA–chitosan–HAp. One of the main challenges for preparing polymer and nHAp composites as bone scaffolds is physicochemical homogeneity. Correia et al. [54][31] developed a new procedure to fabricate a nanocomposite composed of in situ growth of nHAp coated with alginate (ALG), overcoming the problem. Then, they mixed nHAp/ALG nanocomposites with polyvinyl alcohol (PVA) to obtain nanofiber matrix scaffolds with electrospinning.
Beta-tricalcium phosphate (β-TCP) is an osteoconductive material that has been used in clinical applications for several years, and it has also been found that β-TCP can transform into HAp under stimulation of the osteoclastic degradation environment in vitro [55][32]. Huang et al. [56][33] established an organic, solvent-free, injectable, mechanically strong, and biodegradable material by incorporating different concentrations of β-TCP into PCL with the intention of use for medical purposes. Xu. et al. reported [57][34] that a hydrophobic derivative of agarose, agarose acetate (AGA), was blended with the bioactive material β-TCP to assemble AGA/β-TCP nanofibrous membranes through an electrospinning process. After the assembly of β-TCP, the hydrophilicity and mechanical properties of agarose acetate were significantly improved. rBMSCs expressed higher proliferation and osteogenic differentiation levels on nanofibrous membranes containing the β-TCP matrix. In addition, the nanofibrous membranes showed no accessible inflammatory response in vivo during 4 weeks of implantation.

References

  1. Galindo, T.G.P.; Chai, Y.; Tagaya, M. Hydroxyapatite Nanoparticle Coating on Polymer for Constructing Effective Biointeractive Interfaces. J. Nanomater. 2019, 2019, 6495239.
  2. Tsai, S.W.; Yu, W.X.; Hwang, P.A.; Huang, S.S.; Lin, H.M.; Hsu, Y.W.; Hsu, F.Y. Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO-CaCO3 Nanofibers with a Mesoporous Structure as Drug Delivery Carriers. Pharmaceutics 2018, 10, 179.
  3. Lino, A.B.; McCarthy, A.D.; Fernández, J.M. Evaluation of strontium-containing PCL-PDIPF scaffolds for bone tissue engineering: In vitro and in vivo studies. Ann. Biomed. Eng. 2019, 47, 902–912.
  4. Tsai, S.-W.; Hsu, Y.-W.; Pan, W.-L.; Vadivelmurugan, A.; Hwang, P.-A.; Hsu, F.-Y. Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior. J. Funct. Biomater. 2022, 13, 168.
  5. Shoaib, M.; Bahadur, A.; Iqbal, S.; Al-Anazy, M.M.; Laref, A.; Tahir, M.A.; Channar, P.A.; Noreen, S.; Yasir, M.; Iqbal, A.; et al. Magnesium doped mesoporous bioactive glass nanoparticles: A promising material for apatite formation and mitomycin c delivery to the MG-63 cancer cells. J. Alloys Compd. 2021, 866, 159013.
  6. Rizwan, M.; Genasan, K.; Murali, M.R.; Raghavendran, H.R.B.; Alias, R.; Cheok, Y.Y.; Wong, W.F.; Mansor, A.; Hamdi, M.; Basirun, W.J.; et al. In vitro evaluation of novel low-pressure spark plasma sintered HA–BG composite scaffolds for bone tissue engineering. RSC Adv. 2020, 10, 23813–23828.
  7. Sukanya, V.S.; Mohanan, P.V. Degradation of Poly(ε-caprolactone) and bio-interactions with mouse bone marrow mesen-chymal stem cells. Colloids Surf. B Biointerfaces 2018, 163, 107–118.
  8. Garot, C.; Bettega, G.; Picart, C. Additive Manufacturing of Material Scaffolds for Bone Regeneration: Toward Application in the Clinics. Adv. Funct. Mater. 2020, 31, 2006967.
  9. Kalluri, L.; Duan, Y. Parameter Screening and Optimization for a Polycaprolactone-Based GTR/GBR Membrane Using Taguchi Design. Int. J. Mol. Sci. 2022, 23, 8149.
  10. Wu, D.T.; Munguia-Lopez, J.G.; Cho, Y.W.; Ma, X.; Song, V.; Zhu, Z.; Tran, S.D. Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine. Molecules 2021, 26, 7043.
  11. Nyberg, E.; Rindone, A.; Dorafshar, A.; Grayson, W.L. Comparison of 3D-Printed Poly-ɛ-Caprolactone Scaffolds Functionalized with Tricalcium Phosphate, Hydroxyapatite, Bio-Oss, or Decellularized Bone Matrix. Tissue Eng. Part A 2017, 23, 503–514.
  12. Cho, Y.S.; Gwak, S.J.; Cho, Y.S. Fabrication of Polycaprolactone/Nano Hydroxyapatite (PCL/nHA) 3D Scaffold with Enhanced In Vitro Cell Response via Design for Additive Manufacturing (DfAM). Polymers 2021, 13, 1394.
  13. Gautam, S.; Sharma, C.; Purohit, S.D.; Singh, H.; Dinda, A.K.; Potdar, P.D.; Chou, C.F.; Mishra, N.C. Gelatin-polycaprolactone-nanohydroxyapatite electrospun nanocomposite scaffold for bone tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2021, 119, 111588.
  14. Naudot, M.; Garcia, A.G.; Jankovsky, N.; Barre, A.; Zabijak, L.; Azdad, S.Z.; Collet, L.; Bedoui, F.; Hébraud, A.; Schlatter, G.; et al. The combination of a poly-caprolactone/nano-hydroxyapatite honeycomb scaffold and mesenchymal stem cells promotes bone regeneration in rat calvarial defects. J. Tissue Eng. Regen. Med. 2020, 14, 1570–1580.
  15. Tsai, S.-W.; Yu, W.-X.; Hwang, P.-A.; Hsu, Y.-W.; Hsu, F.-Y. Fabrication and Characteristics of PCL Membranes Containing Strontium-Substituted Hydroxyapatite Nanofibers for Guided Bone Regeneration. Polymers 2019, 11, 1761.
  16. Kade, J.C.; Dalton, P.D. Polymers for Melt Electrowriting. Adv. Healthc. Mater. 2021, 10, 2001232.
  17. Wang, Z.; Wang, H.; Xiong, J.; Li, J.; Miao, X.; Lan, X.; Liu, X.; Wang, W.; Cai, N.; Tang, Y. Fabrication and in vitro evaluation of PCL/gelatin hierarchical scaffolds based on melt electrospinning writing and solution electrospinning for bone regeneration. Mater. Sci. Eng. 2021, 28, 112287.
  18. Zerankeshi, M.M.; Bakhshi, R.; Alizadeh, R. Polymer/metal composite 3D porous bone tissue engineering scaffolds fabricated by additive manufacturing techniques: A review. Bioprinting 2022, 25, e00191.
  19. Hosseini, E.S.; Dervin, S.; Ganguly, P.; Dahiya, R. Biodegradable Materials for Sustainable Health Monitoring Devices. ACS Appl. Bio Mater. 2021, 4, 163–194.
  20. Zhao, D.; Zhu, T.; Li, J.; Cui, L.; Zhang, Z.; Zhuang, X.; Ding, J. Poly(lactic-co-glycolic acid)-based composite bone-substitute materials. Bioact. Mater. 2020, 6, 346–360.
  21. Zheng, S.; Guan, Y.; Yu, H.; Huang, G.; Zheng, C. Poly-L-lysine-coated PLGA/poly (amino acid)-modified hydroxyapatite porous scaffolds as efficient tissue engineering scaffolds for cell adhesion, proliferation, and differentiation. New J. Chem. 2019, 43, 9989–10002.
  22. Mondal, S.; Pal, U. 3D hydroxyapatite scaffold for bone regeneration and local drug delivery applications. J. Drug Deliv. Sci. Technol. 2019, 53, 101131.
  23. Li, L.; Song, K.; Chen, Y.; Wang, Y.; Shi, F.; Nie, Y.; Liu, T. Design and Biophysical Characterization of Poly (l-Lactic) Acid Microcarriers with and without Modification of Chitosan and Nanohydroxyapatite. Polymers 2018, 10, 1061.
  24. Wang, D.X.; He, Y.; Bi, L.; Qu, Z.H.; Zou, J.W.; Pan, Z.; Fan, J.J.; Chen, L.; Dong, X.; Liu, X.N.; et al. Enhancing the bioactivity of Poly(lactic-co-glycolic acid) scaffold with a nano-hydroxyapatite coating for the treatment of segmental bone defect in a rabbit model. Int. J. Nanomed. 2013, 8, 1855–1865.
  25. Mao, D.; Li, Q.; Bai, N.; Dong, H.; Li, D. Porous stable poly (lactic acid)/ethyl cellulose/hydroxyapatite composite scaffolds prepared by a combined method for bone regeneration. Carbohydr. Polym. 2018, 180, 104–111.
  26. Islam, N.; Dmour, I.; Taha, M.O. Degradability of chitosan micro/nanoparticles for pulmonary drug delivery. Heliyon 2019, 5, e01684.
  27. Tabassum, N.; Ahmed, S.; Ali, M.A. Chitooligosaccharides and their structural-functional effect on hydrogels: A review. Carbohydr. Polym. 2021, 261, 117882.
  28. Acevedo, C.A.; Olguín, Y.; Briceño, M.; Forero, J.C.; Osses, N.; Díaz-Calderón, P.; Jaques, A.; Ortiz, R. Design of a biodegradable UV-irradiated gelatin-chitosan/nanocomposed membrane with osteogenic ability for application in bone regeneration. Mater. Sci. Eng. C 2019, 99, 875–886.
  29. Wang, Y.; Zhao, Z.; Liu, S.; Luo, W.; Wang, G.; Zhu, Z.; Ma, Q.; Liu, Y.; Wang, L.; Lu, S.; et al. Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model. BMC Musculoskelet. Disord. 2022, 23, 557.
  30. Abazari, M.F.; Nejati, F.; Nasiri, N.; Khazeni, Z.A.S.; Nazari, B.; Enderami, S.E.; Mohajerani, H. Platelet-rich plasma incorporated electrospun PVA-chitosan-HA nanofibers accelerates osteogenic differentiation and bone reconstruction. Gene 2019, 720, 144096.
  31. Correia, G.S.; Falcão, J.S.A.; Castro Neto, A.G.; Silva, Y.J.A.; Mendonça, L.T.B.; Barros, A.O.S.; Santos-Oliveira, R.; de Azevedo, W.M.; Alves Junior, S.; Santos, B.S. In situ preparation of nanohydroxyapatite/alginate composites as additives to PVA electrospun fibers as new bone graft materials. Mater. Chem. Phys. 2022, 282, 125879.
  32. Diez-Escudero, A.; Espanol, M.; Beats, S.; Ginebra, M.P. In vitro degradation of calcium phosphates: Effect of multiscale porosity, textural properties and composition. Acta Biomater. 2017, 60, 81–92.
  33. Huang, S.H.; Hsu, T.T.; Huang, T.H.; Lin, C.Y.; Shie, M.Y. Fabrication and characterization of polycaprolactone and tricalcium phosphate composites for tissue engineering applications. J. Dent. Sci. 2017, 12, 33–43.
  34. Xu, Z.; Zhao, R.; Huang, X.; Wang, X.; Tang, S. Fabrication and biocompatibility of agarose acetate nanofibrous membrane by electrospinning. Carbohydr. Polym. 2018, 197, 237–245.
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