Mussel-inspired polydopamine decorated silane modified-electroconductive gelatin-PEDOT:PSS scaffolds for bone regeneration

May combine two claims.

PDA layer formation reduced the size of pores while maintaining scaffold uniformity.

“It was found that scaffolds had interconnected porous structures, so the PDA layer formation reduced the size of pores while maintaining scaffold uniformity.”

May combine two claims.

For surface-modified scaffolds, biodegradation rate was (8 ± 1)% after 2 weeks and (10 ± 1)% after 3 weeks.

“For surface-modified scaffolds, the biodegradation rate after 2 weeks reached (8 ± 1)%, after 3 weeks it was (10 ± 1)%.”

May combine two claims.

Coating gelatin-PEDOT:PSS constructs with PDA improved their mechanical properties and ability to resist biodegradation.

“As indicated, coating the gelatin-PEDOT:PSS constructs with PDA also improved their mechanical properties and their ability to resist biodegradation.”

May combine two claims.

PDA surface modification deposited a homogeneous PDA layer on the scaffold surface, resulting in a rougher surface.

“As a result of the surface modification, a homogeneous layer of PDA was deposited on the surface (Fig. 1C), resulting in a rougher surface.”

May combine two claims.

Uncoated scaffolds degraded 19.6% more rapidly after two weeks, 41.5% more after three weeks, and 51.3% more after four weeks than coated scaffolds.

“Un-coated scaffolds degrade 19.6% more rapidly after two weeks than coated scaffolds, followed by a 41.5% increase after three weeks, and a 51.3% increase after four weeks.”

May combine two claims. The quote only partly states this claim.

PDA coating decreased the average pore size of gelatin-PEDOT:PSS scaffolds from 239 ± 39 μm to 122 ± 39 μm, a statistically significant difference (p < 0.001).

“As a result of the PDA coating, the average pore size decreased substantially from 239 ± 39 μm to 122 ± 39 μm (Fig. 1E).”

• Also stated in: § Morphology observations · boosted

  “Average pore size of modified and un-modified scaffolds. (Difference is extremely statistically significant (***p < 0.001)).”

• Also stated in: § Morphology observations · hedged

  “It is evident from the considerable standard deviation of the mentioned measurements that there are differences in pore sizes between freeze-dried scaffolds with and without coatings.”

May combine two claims.

After four weeks in PBS, gelatin-PEDOT:PSS scaffolds showed signs of degradation (loosened pore walls) and greater microstructural damage than PDA-coated scaffolds.

“As a result of immersion of scaffolds in PBS solution for four weeks, the gelatin-PEDOT:PSS scaffolds showed signs of degradation, such as loosened pore walls, and there was a higher degree of damage to the microstructure than in the PDA-coated scaffolds.”

May combine two claims.

Cells formed filopodia in PDA-modified structures, whereas the gelatin-PEDOT:PSS sample showed weaker cell adhesion and spreading.

“According to the FE-SEM micrographs, the cells formed filopodia in modified structures with PDA (Fig. 5B); however, the gelatin-PEDOT:PSS sample showed weaker cell adhesion and spreading (Fig. 5A).”

• AssumptionRests on an assumption: A stimulating framework must be provided for bone cells in the form of 3D structures (scaffolds) to heal large bone defects.

May combine two claims.

After immersion in SBF, calcium phosphate rich crystalline layers are shown on the surface of both scaffold types, but PDA-coated samples displayed higher intensity of characteristic HA peaks.

“After immersion of samples in SBF, calcium phosphate rich crystalline layers are shown on the surface of both type of scaffolds. Nevertheless, PDA-coated samples displayed a higher intensity of the characteristic HA peaks.”

Classified as probably not a substantial claim. May combine two claims.

Gelatin is formed by hydrolyzing collagen and is regularly used in bone regeneration due to its hydrophilicity, biodegradability, RGD sequences, simulation of bone's organic matrix phase, and non-immunogenicity.

“Gelatin is a polymer that is formed by hydrolyzing collagen, and is regularly used in bone regeneration due to its hydrophilicity, biodegradability, RGD sequences, simulation of bone's organic matrix phase, and non-immunogenicity.14”

• cites [14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Freeze-dried Sr-doped bioactive glass/chitosan composite scaffolds had a porous structure meeting the optimal pore size required for bone TE and developed bioactivity and cell activity.

“Kuo et al.8 fabricated Sr-doped bioactive glass (BG)/chitosan composite scaffolds via freeze-drying technique. A porous structure was obtained that met the optimal pore size required for bone TE, allowing the scaffolds to develop bioactivity and cell activity.”

• cites [8]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Mechanical deformation of bone compresses its tubular structure, causing ion flow through the canalicular system and creating a localized electromagnetic field that is more intense at thinner sites due to greater strain; osteoblasts initiate bone formation when they detect this strain-induced EMF.

“By compressing the tubular structure of bone during mechanical deformation, a flow of bone-containing ions occurs through the canalicular system, creating a localized electromagnetic field (EMF) that results more intense at thinner sites of the bone due to a greater strain. When the strain-induced EMF is detected, osteoblasts will initiate bone formation.27,28”

• cites [27]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [28]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Freeze-dried graphene-oxide containing PHEMA-gelatin scaffolds had randomly-oriented interconnected pores.

“Further, Nokoorani et al.9 synthesized graphene-oxide containing poly hydroxyethyl methacrylate (PHEMA)-gelatin scaffolds by freeze-drying, which allowed the constructs to have randomly-oriented interconnected pores.”

• cites [9]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Electrical stimulation influences osteoblast adhesion, proliferation, differentiation, protein synthesis, and bone formation by altering cytoskeleton structure and controlling ion channels.

“Moreover, electrical stimulation has been shown to influence osteoblast adhesion, proliferation, differentiation, protein synthesis, and finally bone formation by altering the structure of the cytoskeleton in bone tissue and controlling ion channels.29”

• cites [29]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

GPTMS is a promising bioactive gelatin modifier for biomineralization and osteogenic performance, and is suitable for chemical cross-linking because it contains amine-friendly coupling agents and hydrolysable functional groups.

“In this context, due to the importance of biomineralization and osteogenic performance in bone regeneration, a bioactive gelatin modifier ((3-glycidyloxypropyl) trimethoxy silane (GPTMS)) is a promising candidate. GPTMS is suitable for chemical cross-linking because it contains amine-friendly coupling agents and hydrolysable functional groups.18”

• cites [18]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Scaffolds containing electrically conductive components provide a favorable environment for osteoblast proliferation and accelerate tissue regeneration.

“Scaffolds containing electrically conductive components, from electroconductive polymeric nanofibers22,23 to metal nanoparticles,24,25 have been shown to provide a favorable environment for the proliferation of osteoblasts, thereby contributing to accelerating tissue regeneration.”

• cites [22]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [23]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [24]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Gelatin's dissolution rate after interaction with water is promoted by amines and hydroxyl functional groups, and cross-linking can overcome this problem.

“However, dissolution rate after interaction with water molecules is promoted, arising from amines and hydroxyl functional groups present in the chemical structure. This problem could be overcome by applying cross-linking techniques.16,17”

• cites [16]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [17]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Bone has self-healing capacity, but large defects require external interventions to regenerate effectively.

“In spite of the fact that bone has a self-healing capacity,1 large defects will require external interventions in order to regenerate effectively.”

• cites [1]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Selection of appropriate materials with chemical composition and mechanical properties similar to the target tissue is a challenge in tissue engineering.

“One of the challenges of TE is the selection of appropriate materials with chemical composition and mechanical properties similar to those of the target tissue.12”

• cites [12]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Existing therapeutic substrates have drawbacks (poor restoration of biochemical and biomechanical function, lack of porosity, unsuitable durability, loosening, and toxic byproducts with pH changes causing inflammation) that prevent satisfactory repair of large bone defects.

“While some therapeutic substrates have shown promising results, there are a number of drawbacks (poor restoration of biochemical and biomechanical function, lack of porosity, unsuitable durability of products as well as loosening and toxic byproducts with pH changes causing inflammation, etc.) that prevent satisfactory results in the repair of large bone defects.2,3”

• cites [2]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [3]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

GPTMS is non-toxic and can induce biomineralization (hydroxyapatite formation), which is important in bone regeneration.

“It has been found that this non-toxic cross-linker can induce biomineralization (hydroxyapatite formation) which is important in bone regeneration.19”

• cites [19]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The peptide sequence of glycine, proline, and hydroxyproline in gelatin scaffolds boosted bone marrow stem cell attachment and accelerated bone regeneration.

“Nouri-Felekori et al.15 showed that the peptide sequence of glycine, proline, and hydroxyproline in gelatin scaffolds boosted bone marrow stem cell attachment and accelerated bone regeneration.16”

• cites [15]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [16]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim. May combine two claims.

Freeze-dried scaffolds of pure PEDOT:PSS significantly enhanced gene expression and ALP activity in MC3T3-E1 cells after 4 weeks, suggesting potential use in bone tissue regeneration.

“Guex et al.32 demonstrated that freeze-dried scaffolds of pure PEDOT:PSS significantly enhanced gene expression and alkaline phosphatase (ALP) activity in MC3T3-E1 cells after 4 weeks, suggesting that this scaffold could potentially be used in the regeneration of bone tissue.”

• cites [32]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Freeze-drying allows scaffolds to achieve complex geometry, high porosity, homogeneous pores, and interconnected pores.

“The freeze-drying technique allows to achieve a complex scaffold geometry, as well as high porosity, homogeneous pores, and interconnected ones.7”

• cites [7]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• AssumptionRests on an assumption: The porous structure of freeze-dried scaffolds affects tissue ingrowth and simulates the microstructure of cancellous bone.

May combine two claims.

Surface functionalization strategies can provide a suitable surface for pre-adsorption of proteins and for enhancing cell adhesion, proliferation, and osteogenic differentiation.

“Surface functionalization strategies can provide a suitable surface for pre-adsorption of proteins and for enhancing cell adhesion, proliferation, and osteogenic differentiation.33”

• cites [33]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

PDA surface modification enhances the stability and long-term durability of the scaffolds.

“indicating enhanced stability and long-term durability of the scaffolds after surface modification.”

May combine two claims.

Silane coupling agents such as GPTMS can positively influence bioactivity due to Si ions and stimulate apatite growth.

“It has been shown that silane coupling agents, such as GPTMS, can positively influence the bioactivity behavior of constructs due to the presence of Si ions, and therefore this compound can stimulate the growth of apatite.82”

• cites [82]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

PDA contributes to improved adhesion and proliferation of MC3T3-E1 cells and upregulation of ALP activity and osteogenic-related gene expression.

“PDA was also found to contribute to an improved adhesion and proliferation of MC3T3-E1 cells as well as to the upregulation of ALP activity and the expression of osteogenic-related genes.”

• cites [40]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

In aqueous media, gelatin degrades through hydrolysis, and its cross-linking with GPTMS enhances its resistance to degradation.

“In aqueous media, gelatin is degraded through the process of hydrolysis, and its cross-linking with GPTMS enhances its resistance to degradation, as demonstrated by Nouri-Felekori et al.77”

• cites Nouri-Felekori et al.77Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

PDA coating improves water absorption capacity and provides a hydrophilic construct for better cellular interactions, resulting in high ECM formation.

“According to Patra et al.,75 PDA coating improves water absorption capacity and therefore, provides a hydrophilic construct for better cellular interactions, resulting in a high level of extracellular matrix (ECM) formation.”

• cites Patra et al.,75Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Many molecules in the human body, including H2O2, microorganisms, and free radicals, can cause oxidative degradation of PDA molecules.

“Many molecules in the human body, including H2O2, microorganisms, and free radicals, can cause oxidative degradation of PDA molecules.68”

• cites [68]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Deposited PDA adheres to the inner wall of scaffolds and narrows pore sizes, explaining the statistically significant difference between coated and uncoated scaffolds.

“As deposited PDA adheres to the inner wall of scaffolds, it narrows pore sizes, thus making the difference between coated and uncoated scaffolds statistically significant.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Nano-hydroxyapatite particles coated with PDA and incorporated into PCL matrix create a bioactive and cytocompatible scaffold that accelerates apatite layer formation.

“Another study has shown that nano-hydroxyapatite particles coated with PDA and incorporated into PCL matrix create a bioactive and cytocompatible scaffold that accelerates the formation of apatite layers.83”

• cites [83]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

PDA serves as a site for anchoring cells and incorporating biological molecules.

“In addition, PDA serves as a site for anchoring cells and incorporating biological molecules.37”

• cites [37]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Each experiment was repeated five times.

“Each experiment was repeated five times”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

After PDA coating, formation of HA on poly(l-lactide) fibrous membrane was significantly accelerated and hydrophilicity was greatly improved.

“For example, after PDA coating, Chen et al.40 demonstrated that not only was the formation of HA on poly(l-lactide) fibrous membrane significantly accelerated, but also their hydrophilicity was greatly improved.”

• cites [40]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Previously, the authors demonstrated a positive effect on controlling the biodegradation rate of alginate dialdehyde-gelatin scaffolds when modified with PDA.

“Previously, we have demonstrated a positive effect on controlling the biodegradation rate of alginate dialdehyde-gelatin scaffolds when modified with PDA.79”

• cites [79]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

In Dimassi et al. study, formation of spherical particles on PDA-coated chitosan nanofibers was observed and analyzed by XRD and FE-SEM.

“At the same time, in Dimassi et al. study84 the formation of spherical particles on the surface of PDA-coated chitosan nanofibers was observed and analyzed by XRD and FE-SEM.”

• cites Dimassi et al.84Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Vona et al. demonstrated that PDA coating of living diatom microalgae enhanced their degradation resistance in acidic media.

“Besides, Vona et al.80 demonstrated that PDA coating of living diatom microalgae also enhanced their degradation resistance in acidic media.”

• cites Vona et al.80Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Successful PDA deposition on the scaffold can be determined by the change in color from light blue to dark brown.

“As shown by Han et al.,46 successful PDA deposition on the scaffold can be determined by the change in color from light blue to dark brown.”

• cites Han et al.,46Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

It generally takes two months for the defect site to undergo endochondral ossification after the cartilaginous calluses have been bridged.

“It generally takes two months for the defect site to undergo endochondral ossification after the cartilaginous calluses have been bridged.”

• cites [76]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Peaks at 500 and 1050 cm−1 are attributed to PO43− and C-O asymmetric stretching is observed at 1400 cm−1.

“Peaks at 500 and 1050 cm−1 are attributed to PO43− and C–O asymmetric stretching is observed at 1400 cm−1.87”

• cites [87]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

In damaged tissue, cartilaginous calluses form within two weeks.

“In damaged tissue, cartilaginous calluses form within two weeks.”

• cites [76]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Following the initiation of bone regeneration, bone remodeling can begin as early as three to four weeks later.

“Following the initiation of bone regeneration, bone remodeling can begin as early as three to four weeks later.76”

• cites [76]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Ca2+ ions can be adsorbed at the interface, and consequently PO43− ions from SBF are attracted to the surface for nucleating calcium phosphate.

“Accordingly, Ca2+ ions can be adsorbed at the interface, and in consequence, PO43− ions from SBF are attracted to the surface for finally nucleating calcium phosphate.91”

• cites [91]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The mechanism and kinetics of biodegradation are affected by factors including chemical composition, hydrophilicity, pore size and shape, and surface area.

“The mechanism and kinetic of biodegradation are affected by a variety of factors including chemical composition, hydrophilicity, pore size and shape, and surface area.17”

• cites [17]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.