A New Biomaterial Derived from Aloe vera—Acemannan from Basic Studies to Clinical Application
Abstract
:1. Introduction
2. Manufacturing Process of AC Products
2.1. Crude Extraction
2.2. Separation and Purification
2.3. Structure Identification
3. Application Forms of AC
3.1. AC Particle
3.2. AC Sponge
3.3. AC Hydrogel and Aerogel
3.4. AC Film
4. Effect of Acetyl Group on Bioactivity of AC
4.1. Acetylation Modification of Polysaccharide
4.2. Effect of Acetyl Groups on Biological Activity of Polysaccharides
4.3. Effect of Different Degrees of Acetylation Modification on AC
5. Biological Functions of AC
5.1. Immunoregulation
5.2. Antiviral Effect
5.3. Anti-Tumor Effect
5.4. Dental Tissue Regeneration
5.5. Osteogenesis
5.6. Soft Tissue Healing
6. Advances in the Clinical Application of AC
6.1. Regeneration of Dental Pulp–Dentin Complex
6.2. Bone Regeneration
6.2.1. Osteogenesis after Alveolar Surgery
6.2.2. Bone Augmentation in Oral Implantation Area
6.2.3. Repair of Periodontal Tissue after Treatment of Periodontitis
6.3. Treatment of Skin and Mucosal Disease
6.4. Reduction in Blood Sugar and Blood Lipids
7. Combined Application of AC and Other Compounds
7.1. Combining AC with Polysaccharide
7.1.1. Chitosan (CS)
7.1.2. Alginate (ALG)
7.1.3. Glycosaminoglycan (GAG)
7.2. Combining AC with Collagen (Col)
7.3. Combining AC with Lipids
7.4. Combining AC with Plants
7.5. Combining AC with Other Compounds
8. Conclusions and Prospects
8.1. Using Computer-Aided Drug Design (CADD) Systems for Drug Efficacy Analysis
8.2. Druggability Analysis of AC
8.3. Toxicity Analysis of AC
8.4. Exploring the Relationship between Surface Structure and Molecular Structure and Drug Activity
8.5. Limitations of AC Application in Tissue Engineering
8.6. Developing and Perfecting the Application Form of AC
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AC | Acemannan |
CS | Chitosan |
DeAC | Deacetylated acemannan |
FD | Freeze-drying |
IFD | Industrial freeze-drying |
SD | Spray-drying |
RWD | Refractance window drying |
RZD | Radiant zone drying |
SEM | Scanning electron microscopy |
PDLCs | Periodontal ligament cells |
PVA | Polyving akohol |
LPS | Lipopolysaccharide |
TCs | T cells |
NO | Nitric oxide |
INF-γ | Interferon-γ |
TNF-α | Tumor necrosis factor-α |
IL-1 | Interleukin-1 |
HIV | Human immunodeficiency virus |
FIV | Feline immunodeficiency virus |
BRM | Biological response modulators |
CVB3 | Coxsackievirus B3 |
NDV | Newcastle disease virus |
IBDV | Infectious bursal disease virus |
PAG | processed Aloe vera gel |
BMP-2 | Bone morphogentic protein-2 |
MTA | Mineral trioxide aggregate |
PDPCs | Primary human dental pulp cells |
TLR-2 | Toll-like receptor 2 |
COL-1 | Type I collagen |
FC | Formocresol |
BMSCs | Bone marrow mesenchymal stem cells |
Runx2 | Runt-related transcription factor 2 |
GDF-5 | Growth differentiation factor 5 |
DPC | Direct pulp capping |
CBCT | Cone-beam computed tomography |
GBR | Guided bone regeneration |
DBB | Deproteinized bovine bone |
ISQ | Implant stability quotient |
AV | Aloe vera |
ALN | Alendronate |
mSBI | Modified gingival sulcus bleeding index |
GTR | Guided tissue regeneration |
GAG | Glycosaminoglycan |
ALG | Alginate |
Col | Collagen |
SA | Stearic acid |
SLN | Solid lipid nanoparticles |
AZT | Zidovudine |
ACY | Acyclovir |
CADD | Computer aided drug design |
NOEL | No observed effect level |
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Function | Source | Dose/Form | Cell/Animal | Results | Ref |
---|---|---|---|---|---|
Immunomodulation | Freeze-dried gel | 0.5% (solution) | T cells from human PBMC |
| [60] |
Freeze-dried gel | 100 μg/mL (solution) | Immature dendritic cells (mouse) |
| [61] | |
Fresh gel | 1–8 mg/mL (hydrogel) | Macrophage cells (rats) |
| [62] | |
Freeze-dried gel | 0.5–5.0 mg/mL (gel) | T cells from human PBMC |
| [63] | |
Fresh gel | 2 mg/mL (solution) | Splenocytes and macrophages (chicken) |
| [65] | |
Fresh gel | 100 μg/mL (solution) | RAW 264.7 cells (mouse) |
| [66] | |
Fresh gel | 500 μg/mL (solution) | Macrophage cells (chicken) |
| [67] | |
Fresh gel | 1–2 mg/mL (solution) | Hematopoietic progenitors (mouse) |
| [68,69] | |
Fresh gel | 50 mg/kg (pellet) | Splenocytes (mouse) |
| [70] | |
Antiviral effect | Fresh gel | 31.25–62.5 mg/mL (solution) | CEM-SS1 and MT-2(2) cells |
| [72] |
Fresh gel | 2–100 mg/kg (solution) | Lymphocytes (cats) |
| [73] | |
Lyophilized powder | 0.5 mg/kg (solution) | Mouse |
| [76] | |
Lyophilized powder | 0.1–0.5 mg/mL (solution) | Chicken |
| [77] | |
Anti-tumor effect | Fresh gel | Solution | Macrophages (mouse) |
| [79] |
Fresh gel | 200–400 mg/kg (gel) | Mouse |
| [80] | |
Fresh gel | - | Mouse |
| [81] | |
Regeneration of dental tissue | Fresh gel | 0.25–1 mg/mL (solution) | Periodontal fibroblasts and pulpal fibroblasts |
| [84] |
Fresh gel | 1–8 mg/mL (sponge) | Dental pulp cells (rats) |
| [85] | |
Fresh gel | 0.5–4 mg/mL (Sponge) | Dental pulpal cells (rats) |
| [86] | |
Fresh gel | 0.5–8 mg/mL (solution) | Cementoblasts |
| [87] | |
Bone formation | Fresh gel | 2–8 mg/mL (sponge) | BMSCs (rats) |
| [88] |
Fresh gel | Sponge | Rats |
| [35] | |
Fresh gel | 0.25–4 mg/mL (sponge) | PDLCs (dogs) |
| [38] | |
Soft tissue healing | Fresh gel | 150 μg/mL (solution) | Skin fibroblasts (mouse) |
| [89] |
Fresh gel | 0.01–10 mg/mL (solution) | Human gingival fibroblasts |
| [90] | |
Fresh gel | 2–16 mg/mL (solution) | GFs (rats) |
| [91] | |
Fresh gel | 25–75% (hydrogel) | Rats |
| [40] | |
Fresh gel | Gel | Sheep |
| [92] |
Clinical Application | Year | Application Field | Sample Size (Unit) | Follow-Up Time | Form/Dose | Control Group | Results | Ref |
---|---|---|---|---|---|---|---|---|
Regeneration of pulp–dentin complex | 2022 | Apexogenesis | 2 (people) | 12 months | Sponge | - | Preserved pulp vitality and form apical stop. | [100] |
2020 | Pulpotomy (young permanent teeth) | 50 (tooth) | 12 months | Sponge | MTA | Induced continued root formation. | [99] | |
2017 | Pulpotomy (deciduous teeth) | 46 (tooth) | 12 weeks | Sponge | FC | Promoted dentin bridge formation. | [98] | |
2015 | DPC (deciduous teeth) | 42 (tooth) | 6 months | Sponge (0.4 mg) | calcium hydroxide | Promoted dentin bridge and soft tissue formation. | [36] | |
Bone formation | 2023 | Periodontal surgery | 3 (tooth) | 5 years | Sponge | - | Reduced probing pocket depth, increased clinical attachment level, and bone density. | [110] |
2022 | GBR | 20 (people) | 6 months | Particle | DBB | Enhanced dimensional stability of the regenerated tissue. | [107] | |
2021 | Alveolar ridge preservation | 35 (people) | 12 months | Sponge (20, 50 mg) | Spontaneous blood-clotting | Reduced tooth socket volume. | [101] | |
2020 | Lateral sinus augmentation | 1 (people) | 6 months | Sponge (150 mg) | - | Increased bone height significantly. | [105] | |
2019 | Indirect sinus augmentation | 30 (people) | 6 months | Sponge (50 mg) | No-treatment control | Enhanced endo-sinus bone formation greatly. | [34] | |
2019 | Apical surgery | 22 (tooth) | 12 months | Sponge (5, 10 mg) | Spontaneous blood-clotting | Enhanced early bone healing. | [102] | |
2018 | Periodontitis with furcation defects | 90 (people) | 12 months | Gel | ALN | Improved periodontal pocket depth and attachment loss. | [108] | |
2016 | Alveolar ridge preservation | 99 (people) | 3 months | Sponge (50 mg) | Spontaneous blood-clotting | Increased the bone density and tooth socket healing. | [37] | |
2002 | Alveolar osteitis | 1194 (people) | 7 days | Hydrogel | Gelfoam | Reduced the incidence of alveolar osteitis. | [103] | |
Treatment of skin and mucosal diseases | 2013 | Aphthous ulcer | 100 (people) | 7 days | Gel (0.5%) | Triamcinolone | Reduced ulcer size and pain. | [111] |
1998 | Pressure ulcers | 30 (people) | 10 weeks | Hydrogel | Moist saline gauze | Promoted ulcer healing. | [114] | |
Improvement of blood sugar and lipids | 2011 | Advanced Type 2 Diabetes | 35 (people) | 2 months | Capsule (300 mg) | Placebo capsules | Lowered the blood levels of fasting glucose and glycosylated hemoglobin significantly. | [116] |
2011 | Hyperlipidemic Type 2 Diabetes | 67 (people) | 2 months | Capsule (300 mg) | Placebo capsules | Lowered the fasting blood glucose, HbA1c, total cholesterol, and LDL levels significantly. | [117] |
Drug | Application Field | Application Form | Result/Function | Ref |
---|---|---|---|---|
AC + CS | Wound healing | Hydrogel | Weakened the mechanical strength and biological activity of the CS gel with increasing AC. | [118] |
AC + CS | Wound healing | Film | Resulted in strong synergistic effects and leaded to mixed junction zones formation. | [41] |
AC + CS | Osseointegration | Solution | Improved osseointegration with a seamless implant interface. | [119] |
AC + CS | Carrier modification | Solution | Enhanced drug loading capacity. | [120] |
AC + CS | Tissue regeneration | Scaffold | Repaired tissue defects caused by ameloblastoma. | [121] |
AC + ALG | Wound healing | Film | Leaded to more resistant and stable structures. | [41] |
AC + ALG | Antioxidation | Film | Enhanced the antioxidant capacity. | [123] |
AC + ALG + CS | Wound healing | Film | Retained and created a moist environment around the wound to promote its healing. | [42] |
AC + GAG | Bone healing | Scaffold | Binded with a TLR-2 target receptor. | [126] |
Ac + COL | Pulp regeneration | Scaffold | Increased expression of dentin extracellular matrix proteins. | [132] |
AC + SA | Carrier modification | Nanoparticle | Improved hydrophilicity to enhance drug absorption. | [135] |
AC + Caffeate + ALG | Treatment of osteoarthritis | Bead | Promoted ATDC5 chondrocyte-like cell growth and cartilage-like extracellular matrix formation. | [136] |
AC + Curcumin | Wound healing | Hydrogel | Reduced wound healing days greatly. | [138] |
AC + Curcumin | Osseointegration | Hydrogel | Inhibited osteoblast differentiation. | [139] |
AC + Resveratrol | Treatment of skin cancer | Scaffold | Inhibited the growth of A431 skin cancer cells and skin pathogens (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). | [143] |
AC + Moringa oleifera | Osseointegration | Hydrophilic gel | Increased bone contact with implant. | [144] |
AC + Silver salt | Wound healing | Gel | Showed broad-spectrum antimicrobial activity. | [146] |
AC + Honey | Wound healing | Hydrogel | Inhibited the growth of Staphylococcus aureus, Escherichia coli, and candida albicans. | [39] |
AC + AZT or ACY | Antiviral | - | Inhibited the replication of HIV-1 and HSV-1. | [147] |
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Bai, Y.; Niu, Y.; Qin, S.; Ma, G. A New Biomaterial Derived from Aloe vera—Acemannan from Basic Studies to Clinical Application. Pharmaceutics 2023, 15, 1913. https://doi.org/10.3390/pharmaceutics15071913
Bai Y, Niu Y, Qin S, Ma G. A New Biomaterial Derived from Aloe vera—Acemannan from Basic Studies to Clinical Application. Pharmaceutics. 2023; 15(7):1913. https://doi.org/10.3390/pharmaceutics15071913
Chicago/Turabian StyleBai, Yingjie, Yimeng Niu, Shengao Qin, and Guowu Ma. 2023. "A New Biomaterial Derived from Aloe vera—Acemannan from Basic Studies to Clinical Application" Pharmaceutics 15, no. 7: 1913. https://doi.org/10.3390/pharmaceutics15071913
APA StyleBai, Y., Niu, Y., Qin, S., & Ma, G. (2023). A New Biomaterial Derived from Aloe vera—Acemannan from Basic Studies to Clinical Application. Pharmaceutics, 15(7), 1913. https://doi.org/10.3390/pharmaceutics15071913