Preclinical in vivo Performance of Novel Biodegradable, Electrospun Poly(lactic acid) and Poly(lactic-co-glycolic acid) Nanocomposites: A Review
Abstract
:1. Introduction
2. Material Characteristics and Degradation Behavior
3. Biocompatibility in Preclinical Studies
3.1. Aim of the Review on Biocompatibility
3.2. Search Strategy
3.3. Review Process
3.4. Results
3.4.1. Description of Materials
3.4.2. Description of Experimental Methods
Author | Scaffold Components | Scaffold Architecture | Fiber Diameter |
---|---|---|---|
Adegani et al. [33] | PLGA 15% (wt/wt) solution dissolved in DMF/THF coating with willmite nanoparticles | porous structure | 300 ± 500 nm; willmite coating did not affect fiber diameter |
Dinarvand et al. [34] | PLLA dissolved in chloroform with a 4% (w/v) concentration coating with HA, BG, TCP; HA + BG | nanofibrous structure with homogeneous distribution of bioceramics along the surface of PLLA | 822 ± 97 nm |
Jaiswal et al. [35] | PLLA with molecular weight 300,000 Da blend with G (3:1) composited with HA | no information | no information |
Jiang et al. [36] | PLGA (85:15) 10% with molecular weight of 80,000 Da dissolved in a mixture of chloroform + DMF (1:1) mixed with HA (20:1) mixed with HA + SIM (20:1:1) | scaffolds with smooth and nanofibrous morphology | PLGA: 550 ± 50 nm PLGA + HA: 240 ± 30 nm PLGA + HA + SIM: 270 ± 30 nm |
Lee et al. [38] | PLLA (5.7–8.2 dL/g viscosity; Resomer L 214 S) dissolved in HFIP (2 wt % for random, 2.5 wt % for aligned fibers) coating with polydopamine | scaffolds with random and aligned fiber orientation | 1 μm in both structures |
Ko et al. [37] | PLLA (3.3–4.3 dL/g viscosity; Resomer L 210 S) dissolved in trifluorethanol mixed with DBP (1.0:0.2) | nanofibrous scaffold with randomly oriented fibers with a homogeneous distribution | 300–700 nm |
Schneider et al. [9] | PLGA (Resomer) (85:15) with a molecular weight of 380,300 g/mol and 181,900 g/mol blend with TCP nanoparticles (40 wt %) | fibers exhibiting a porous structure, TCP-containing fibers revealed an increased roughness | 5–10 μm |
Schofer et al. [30] | PLLA (Resomer) 4% (w/w) dissolved in DCM incorporation of BMP-2 | three-dimensional non-woven network of nanofibers, fibers showed a porous structure | 775 ± 294 nm |
Shim et al. [31] | PLLA (intrinsic viscosity 0.63 dL/g, molecular weight: 250,000 g/mol); 8% PLLA dissolved in DCM/HFIP or in DCM/DMF or in DCM/acetone with volume ratios (90:10) 3% PLLA in DCM/HFIP (90:10) | PLLA mixture below 2% w/v resulted in beaded fibers, for concentrations > 4%, the fibers fused at the contact points | 400 nm–7 μm |
Yanagida et al. [32] | PLLA (Lactel: intrinsic viscosity: 0.9–1.2 dL/g) dissolved in DMC at 15 wt % mixed or coated, or mixed and coated with HA nanocrystals | PLLA/HA nanocomposite fibers, where HA nanocrystals were mixed into the PLLA matrix as well as coated onto the PLLA surface had submicron-sized dimples on their surfaces | PLLA fibers: 6.1 ± 1.9 μm PLLA/HA mixed: 7.6 ± 1.9 μm |
Author | Animal Model | Defect Size (Diameter) and Wound Treatment | Time of Evaluation | Methods of Evaluation | Area of Regenerated Bone | Histological Results |
---|---|---|---|---|---|---|
Adegani et al. [33] | rats | 8 mm calvarial critical size defects, precise treatment of the wound is not described | 8 weeks | MSCT histology evaluation by two independent radiologists | PLGA + willmite: 70% PLGA: 35% Empty: 5% | No sign of inflammation |
Dinarvand et al. [34] | rats | 8 mm calvarial critical size defects, wound was closed with sutures | 8 weeks | MSCT Digital mammo-graphy histology evaluation by two independent radiologists | PLLA-HA-BG: 63% PLLA-TCP: 44% PLLA-HA: 23% PLLA-BG: 20% PLLA: 13% Empty: 12% | No sign of inflammation |
Jaiswal et al. [35] | rats | 5 mm calvarial critical size defects, pericranium and skin was closed in layers | 6 and 10 weeks | Micro-CT digital X-ray, hematology and serum biochemistry histology evaluation with an image software | 6 weeks: PLLA-G-HA: ≈94% PLLA-HA: ≈64% Empty: 30% PLLA: 26% PLLA-G: 13% 10 weeks: PLLA-G-HA: 98% PLLA-G: 80% PLLA-HA: 76% PLLA: 60% Empty: 34% | No sign of inflammation |
Jiang et al. [36] | rats | 5 mm calvarial defects, wound was closed with sutures | 4 and 8 weeks | Micro-CT histology evaluation with an image software | 4 weeks: PLGA-HA-SIM: ≈4.2% PLGA-HA: <1% Empty: <1% 8 weeks: PLGA-HA-SIM: ≈10% PLGA-HA: <4% Empty: <2% | - |
Lee et al. [38] | mice | 4 mm calvarial critical size defects, wound was closed with sutures | 8 weeks | Micro-CT SEM histology precise method of evaluation is not described | PLLA + DA aligned fibers: 28.86 ± 6.5% PLLA + DA random fibers: 10.58 ± 0.9% PLLA aligned fibers: 5.25 ± 3.7% PLLA random fibers: 3.35 ± 1.8% | No sign of inflammation |
Ko et al. [37] | rats | 8 mm calvarial critical size defects, a polyvinyl membrane was laid over the defects and the wound was closed with sutures | 8 and 12 weeks | Micro-CT nhistology precise method of evaluation is not described | 8 weeks: PLLA: minimal newly formed bone PLLA + DBP: greater extent of newly formed bone than PLLA alone 12 weeks: PLLA: 70% PLLA + DBP: 90% | PLLA: large numbers of inflammatory cells (12 weeks) PLLA + DBP: Minimal inflammatory reactions (12 weeks) |
Schneider et al. [9] | rabbits | 6 mm calvarial non-critical size, wound was closed with sutures | 4 weeks | Radiography Micro-CT histology evaluation with an image software | PLGA/TCP: 34.9 ± 17% Bio Oss: 30.8 ± 14.3% Empty: 28.4 ± 14.9% PLGA: 25.1 ± 14.6% | No sign of inflammation |
Schofer et al. [30] | rats | 5 mm calvarial critical size defects, the wound was closed by suturing the overlaying tissue and skin | 4, 8, and 12 weeks | CCT histology evaluation with an image software | 4 weeks: PLLA/BMP-2: 31% BS: 4% PLLA: 3% Empty: 1% 8 weeks: PLLA/BMP-2: 48% BS: 6% LLA: 5% Empty: 3% 12 weeks: PLLA/BMP-2: 48% BS: 26% PLLA: 2% Empty: 9% | No sign of inflammation |
Shim et al. [31] | rabbits | 8mm calvarial defects Wound was closed with sutures | 2 and 4 weeks | histology | - | 2 weeks: cells (mostly connective tissue and inflammatory cells) penetrated the three-dimensional scaffolds. 4 weeks: new bone formation was observed |
Yanagida et al. [32] | rats | 3 mm calvarial defects Wound was closed with sutures | 4 weeks | histology | - | PLLA: rarely new bone HAP-mixed/coated PLLA: new bone was more elongated |
3.4.3. New Bone Formation at Different Time Points
(1) PLGA
(2) PLLA
3.4.4. Biocompatibility Based on the Descriptive Histological Evaluation
(1) PLGA
(2) PLLA
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Holderegger, C.; Schmidlin, P.R.; Weber, F.E.; Mohn, D. Preclinical in vivo Performance of Novel Biodegradable, Electrospun Poly(lactic acid) and Poly(lactic-co-glycolic acid) Nanocomposites: A Review. Materials 2015, 8, 4912-4931. https://doi.org/10.3390/ma8084912
Holderegger C, Schmidlin PR, Weber FE, Mohn D. Preclinical in vivo Performance of Novel Biodegradable, Electrospun Poly(lactic acid) and Poly(lactic-co-glycolic acid) Nanocomposites: A Review. Materials. 2015; 8(8):4912-4931. https://doi.org/10.3390/ma8084912
Chicago/Turabian StyleHolderegger, Claudia, Patrick R. Schmidlin, Franz E. Weber, and Dirk Mohn. 2015. "Preclinical in vivo Performance of Novel Biodegradable, Electrospun Poly(lactic acid) and Poly(lactic-co-glycolic acid) Nanocomposites: A Review" Materials 8, no. 8: 4912-4931. https://doi.org/10.3390/ma8084912