Nanomaterials-Upconverted Hydroxyapatite for Bone Tissue Engineering and a Platform for Drug Delivery

Figures & data

Figure 1 Some important properties of a bone scaffold.

Figure 2 Methods to synthesize the synthetic HA.

Figure 3 HA reinforced with other materials to form bone scaffold.

Figure 4 Structure of (A) Gram-positive and (B) Gram-negative bacteria.

Figure 5 Chemical structure of chitosan.

Notes: Adapted from Sami El-banna F, Mahfouz ME, Leporatti S, El-kemary M, Hanafy NAN. Chitosan as a Natural Copolymer with Unique Properties for the Development of Hydrogels. Appl Sci. 2019;9(11):2193 (doi.org/10.3390/app9112193).²⁶

Figure 6 Formation of calcium alginate.

Table 1 Effects of OMMT Towards Tensile Strength, Hemocompatibility, Cell Growth and Antibacterial Activity of HA-Based Nanocomposite

	CTS (%wt)	OMMT (%wt)	Tensile Strength (MPa)	Hemocompatible (%)	Proliferation of MG-63 Cells	Antibacterial Activity (mm)
						L. fusiformis	B. cereus	E. coli
ZnCH	95	0	16.16±0.32	5.5	Lowest	12.3±0.62	11.6±0.51	11.259
ZnCHM I	90	5	30.13±0.16	4	Highest	17.2±0.72	12.8±0.62	11.8±0.57
ZnCHM II	85	10	29.80±0.21	5	Moderate	18.0±0.58	13.5±0.58	12.4±0.55
ZnCHM III	80	15	23.07±0.26	7	Higher than control	12.3±0.62	14.1±0.51	12.9±0.68

Notes:Data from Bhowmick A, Lal S, Pramanik N, et al.⁸

Table 2 HA-Based Nanocomposites for Drug Delivery System

HA Nanocomposites	Drug Used	Drug Release Properties	Antibacterial Activity	Reference
HA-alginate	Ciprofloxacin	–	–	[^Citation6]
HA-MWCNTs	Ciprofloxacin	Sustained-release for a month	–	[^Citation3]
HA-K-carrageenan-chitosan	Ciprofloxacin	Sustained-release at 120 hours	A significant zone of inhibition against E. coli and S. aureus	[^Citation88]
Carbonated HA coatings on titanium plates	Gentamicin	Sustained-release up to 24 hours	A high content of gentamicin against S. epidermis	[^Citation103]
HA-coated titanium	Gentamicin	Sustained-release after 48 hours	Partially eliminates S. aureus and S. epidermis	[^Citation79]

Table 3 Recent Patents on Hydroxyapatite-Based Nanocomposites for Bone Tissue Engineering

Patents/Year	Method of Invention	Claims	Reference
CN 110665055/2020	The scaffold is produced by mixing calcium nitrate and ammonium phosphate to synthesize hydroxyapatite, the sericin solution taken from silkworm cocoons after being immersed in a lithium bromide aqueous solution.	A complex porous scaffold derived from sericin and nano-hydroxyapatite used as a carrier to monitor the growth factors of bone morphogen 2 by detecting the loading and release of the osteogenesis process.	[^Citation20]
CN 110898257/2020	Polymerization of polylactide-propylene glycol methacrylate and hydroxyapatite.	The photocurable composite produced for bone tissue engineering to improve the mechanical property, biocompatibility, biodegradability and porosity without using a toxic solvent.	[^Citation114]
CN 110639060/2020	3D bio-printed silk fibroin-based bone tissue engineering scaffold was prepared by mixing the silk fibroin fibers, lithium bromide, gelatin, hydroxyapatite and hyaluronic acid.	The 3D bioprinting silk fibroin produced from a short material preparation process with high solubility property to engage in body metabolism to induce the growth of osteoblast, non-toxic and cheap.	[^Citation63]
CN 109260525/2019	Calcium phosphate-based bioactive ceramic printing ink was prepared by mixing hydroxyapatite, tricalcium phosphate (TCP), binder (PVA) and ethanol. The 3D printing scaffold is produced using three-dimensional inkjet printing, selective laser etching (SLS), stereo light-curing molding and digital light processing (DLP).	The 3D-printing technology is used for controlling the shape and microporous structure of scaffold to repair hard tissue.	[^Citation14]
CN 109758609/2019	The 3D scaffold produced by mixing calcium chloride, zinc chloride, deionized water, creatine phosphate, chitosan and silk fibroin.	The composite that is composed of more than one material is preferred to improve the scaffold performance with a fine method of synthesis, simple and low cost.	[^Citation16]
CN109589450/2019	The method to synthesis-guided bone tissue regeneration is simple by mixing MXene and synthetic hydroxyapatite nanowires in a specific condition.	The addition of MXene as guided bone tissue regeneration material to separate different epithelial tissue in the growing process, as well as act as a supporter for bone scaffold and, potentially, prevent any infection.	[^Citation117]
US 20180071433/2018	The porous scaffold comprised: porous tannin powder particles, dried polyethylene glycol particles, hydroxyapatite, organic acid, formaldehyde solution and biodegradable polymer (polyurethane, polylactic acid, etc).	The bone graft is biocompatible with optimum porosity and pore diameter, high compressive strength and osteocompotent of stem cells stimulate bone growth.	[^Citation99]
CN 108339152/2018	A mixture containing aliphatic polyester-polyethylene glycol block copolymer, Span-80, Tween-60, stabilizer and silver nitrate.	The loaded silver nanoparticles can provide bacteriostatic activity, and the loaded hydroxyapatite provides osteogenic activity.	[^Citation86]
CN 108297396/2018	Mix gelatin, sodium alginate, water, nanoscale hydroxyapatite with the first freeze-drying treatment, curing treatment, cleaning and second freeze drying to produce a bone tissue engineering scaffold.	The 3D bone tissue engineering scaffold is produced through extrusion deposition type 3D printing, and this method will strengthen hydroxyapatite and increase the biological affinity of the scaffold.	[^Citation47]
CN 107982578/2018	The scaffold produced by reacting these materials: β-cyclodextrin (soft segment component for polyurethane synthesis), hexamethylene diisocyanate (hard segment component), nano-hydroxyapatite and stannous octoate (catalyst).	The nanocomposite scaffold has a porous structure with good biocompatibility and mechanical properties and a simple method with low cost.	[^Citation23]
CN 106421894/2017	Hydroxyapatite powder undergoes surface modification by stearic acid, mixing the hydroxyapatite powder and a poly-L-lactic acid solution and electrostatic spinning on a mixed solution.	The scaffold has a connected porous structure that gives a pathway for nutrient transmission, the hydroxyapatite material is not degraded easily, while the product of the degradation process is useful for human metabolism.	[^Citation27]
CN 106512099/2017	The method used in producing bone tissue engineering scaffold is by mixing chitosan, acetic acid, sodium hydroxide, deionized water and calcium chloride and dipotassium phosphate, to generate hydroxyapatite.	The scaffold has high compressive strength (1.5–4.5 MPa), larger pore size, uniform distribution of nano-acicular hydroxyapatite and better biological activity.	[^Citation43]
CN 107158477/2017	The ratio amount of hydroxyapatite/collagen powder added is 0.2–0.1% of lactoferrin then, filter and centrifuge at the suitable condition. The end product will be a freeze-dried process to remove impurities.	The composites have good biocompatibility, and the addition of lactoferrin will improve the osteogenic activity of the composite. The hydroxyapatite/collagen composite can release lactoferrin at an optimum rate.	[^Citation71]
CN 105963789/2016	The scaffold materials comprise gelatin, deionized water, hydroxyapatite, stearic acid (pore former), ethanol and glutaraldehyde (aid in the cross-linking process).	The method used to produce bone tissue scaffold is low cost, uses non-toxic materials, modifies the pore size of the scaffold to an optimum size and strengthens the hydroxyapatite up to 30 MPa.	[^Citation113]
US 20150343117/2015	The method used to produce collagen/HA composites directed press a collagen scaffold into a perfusion chamber of a closed-loop perfusion flow system and constantly delivering a mineralization perfusion fluid via collagen scaffold at an optimum rate and produce collagen/HA composites.	The collagen/HA composites that are prepared using dynamic intrafibrillar mineralization are able to give a stable environment with low cytotoxicity, biodegradable and convenient for human mesenchymal stem cell (hMSC) growth.	[^Citation42]

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