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Table 1 Synthesis strategy, methods and results of natural biomaterials based on novel techniques and tools

From: Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications

Strategies

Natural biomaterials

Methods, the involved strains or cells, and results

References

Novel chassis strains/cells

γ-PGA

Produced in engineering bacteria for high production

[66]

AMPs

Produced in C. reinhardtii for stable expression of AMPs

[71]

PLA & PLGA

Produced in engineered E. coli

[72]

PHAs

Produced in H. bluephagenesis under high salt concentration and non-sterile conditions

[72]

PHAs

Produced in engineered C. glutamicum for PHAs with free exotoxins and endotoxins

[73]

HA

Produced in engineered C. glutamicum for HA with free exotoxins and endotoxins

[73]

Alginate

Produced in engineering bacteria for high production

[96]

Cellulose

Produced in Acetobacteraceae, Gluconacetobacter and Komagataeibacter for a large proportion of cellulose

[76]

Collagen

Produced in engineering bacteria for high production

[99]

Fibroin

Produced in engineered B. subtilis, S. cerevisiae and Chinese hamster ovary cells

[78,79,80]

Synthetic biology tools

PHAs

Manipulated the PHA synthesis-related genes via CRISPR-Cas9

[94]

 

Increased the production of PHB via optimization of ribosomal binding site

[87]

HA

Increased the production of HA via optimization of ribosomal binding site

[88]

Fibroin

Incorporated spider silk protein genes into the Bombyx mori genome via CRISPR-Cas9

[84]

AMPs

Inserted hLYZ gene into the bovine β-casein locus via zinc finger nucleases

[85]

AMPs

Produced cecropin P1 with 31 amino acid residues and hBD-2 in cell-free biosynthesis system

[86]

Metabolic engineering

PHAs

Increased the production of PHA via PadhE, GabD, MCC, UdhA, FadA, FadB, FtsZ and MreB

[91,92,93,94, 96]

HA

Regulated HA via genes DivIVA and FtsZ down or up

[101]

Collagen

Increased the production of human-like collagen via optimization of carbon/nitrogen molar ratios

[99]

Alginate

Metabolic flux analysis shows higher production of alginate acetylation in the cultures with limited oxygen

[98]

Cellulose

Biomaterial properties of bacterial cellulose can be regulated through metabolic flux

[100]

AI & ML

AMPs

Predicted new AMPs via neural network

[102]

HA

Predicted multiple genes expression in a pathway of HA based on AI

[108]

HA

Simplified pathway design of HA via AI

[108]

PHAs

Predicted the Tg of PHAs via recurrent neural network

[108, 109]

Cellulose

Predicted the location of PHA-accumulating bacteria in a mixed microbial culture by recurrent neural network

[111]

Collagen

Deduced the tensile strength of PLA fused deposition models by Taguchi L9 orthogonal array

[108]

Cellulose

Enzymatic kinetics of cellulose synthesis was described by artificial neural networks

[113,114,115,]

  1. PLA Polylactic acid, PLGA Poly (lactic-co-glycolic acid), E. coli Escherichia coli, PHAs Polyhydroxyalkanoate, PHB Polyhydroxybutyrate, HA Hyaluronic acid, γ-PGA Gamma-poly-glutamic acid, AMPs Antimicrobial peptides, hLYZ Human lysozyme, hBD-2 Human beta-defensin 2, Tg Glass Transition temperature, AI Artificial intelligence, ML Machine learning, H. bluephagenesis Halomonas bluephagenesis, C. glutamicum Corynebacterium glutamicum, CRISPR-Cas9 Clustered regularly interspaced short palindromic repeats—CRISPR associated protein 9, adhE Alcohol dehydrogenase, GabD Succinate-semialdehyde dehydrogenase, MCC 2-Methylcitrate cycle, UdhA Pyridine nucleotide transhydrogenase, FadA Acetyl-CoA C-acyltransferase, FadB Fatty acid oxidation complex subunit alpha, FtsZ Cell division protein, MreB Rod shape-determining protein