Table 1 Direct approaches for controlled release of GFs on various substrates for biomedical applications

From: Novel biomaterial strategies for controlled growth factor delivery for biomedical applications

Substrates

GFs

Immobilization approaches

Biological effect

Biomedical applications

Reference

PLGA scaffolds

VEGF

Physical encapsulation

The VEGF released from the polymer scaffolds was over 70% active up to 12 days

Bone regeneration

21

Alginate- sulfate/ alginate scaffolds

VEGF, PDGF, TGF-β1

Physical encapsulation

The triple factor-bound alginate-based porous scaffolds promoted vascularization in vivo

Vascularization

22

Gelatin hydrogel

bFGF

Physical encapsulation

The bFGF loaded hydrogel has stronger regenerative effects on acute vocal fold scarring than that of direct injection of bFGF

Vocal fold regeneration

125

Diblock copolymer matrix

Hepatocy-te growth factor (HGF)

Physical adsorption

The controlled HGF release promoted ECM synthesis and vocal fold regeneration

Vocal fold regeneration

126

PLA porous films

NGF

Encapsulation

This novel strategy significant promoted guided neurite extension from PC12 cells

Peripheral nerve regeneration

127

HA, TCP and neutralized glass ceramic

BMP-2, bFGF

Physical immobilization

Both GFs lose their biological activity after their initial burst on the surfaces of these inorganic carriers in vitro

Bone regeneration

23

Polydioxanone fiber

VEGF

Physical immobilization

VEGF treatment promoted new blood vessels and connective tissue formation

Pulp regeneration

128

Glass slides

BMP-2

LbL self-assembly

The BMP-2 being trapped in the LbL films and remaining their bioactive for more than 10 days

Bone regeneration

129

TCP/HAP granules

BMP-2

LbL self-assembly

LbL films-coated organic granules sequestered significant amounts of BMP-2, and enhanced the osteoinductivity of scaffolds

Bone regenration

130

Anodized titanium

BMP-2, bFGF

LbL self-assembly

LbL films were capable of sustained release of both GFs over 25 days, and increased bone growth

Bone regeneration

131

Polycaprolactone/β-TCP scaffolds

BMP-2, VEGF

LbL self-assembly

LbL films that sequester of BMP-2 VEGF in different ratios in degradable films

Bone regeneration

28

Gelatin based coatings

Nerve growth factor (NGF)

LbL self-assembly

The coatings can be applied to neural electrodes for sustained delivery of NGF to increase neuron density

Alzheimer’s disease treatment

132

PLGA scaffolds

VEGF

Carbodiimide crosslinking

Immobilized VEGF enhanced endothelial cell proliferation

Angiogenesis

133

Fibrin microthreads

HGF

Carbodiimide crosslinking

Myoblast proliferation increased significantly on stiffer, crosslinked, matrix, regardless of the amount of HGF

Skeletal muscle regeneration

134

Polyethylene terephthatalate (PET) surfaces

BMP-2

Carbodiimide crosslinking

BMPs grafted to PET surface promoted osteogenic differentiation of pre-osteoblastic cells

Bone regeneration

135

3D printed polycaprolactone (PCL) scaffolds

BMP-2

Mussel-inspired chemistry

This grafting realized sustained release of BMP-2 and enhanced cell proliferation and osteoconductivity of the scaffolds

Bone regeneration

136

Titanium surfaces

BMP-2

Mussel-inspired chemistry

The immobilization of BMP-2 induced stem cell to osteoblast and mineralization on titanium surfaces

Bone regenrationi

137

Collagen- GAG (CG) matrix

BMP-2, PDGF

Benzophenone (BP) photolitho- Graphy

Both factors could be covalently grafted to the CG matrix in defined patterns

Regenerative medicine application

138

Gelatin-based hydrogel

VEGF

Covalent immobilization

The gelatin-based drug-releasing hydrogel can induce capillary-like tube formation and axonal

Peripheral nerve regeneration

139

Chitosan collagen hydrogels

TGF-β

Covalent conjunction

The biofunctional hydrogel with controlled release of GF promoted chondrogenesis.

Cartilage regeneration

140

Fibrin matrices

PDGF

Covalent immobilization

PDGF conjugated fibrin matrix effectively increased tissue perfusion and induced the growth of a mature neovasculature

Ischemic tissue regeneration

141

Titanium surfaces

BMP-2

Reductive amination reaction

Immobilized BMP-2 at a surface density (>50 ng/cm2) significantly promoted the osteoblast functions

Bone regeneration

38

PLGA microspheres

BMP-2

Bioaffinity tethering

BMP-2-immobilized PLGA microspheres significantly enhanced ALP activity, calcium deposition of MG63 cells

Bone regeneration

142

Synthetic polymer matrix

FGF

Bioaffinity interaction

The EGF release promoted epithelization, collagen deposition, and granulation tissue formation.

Dermal regeneration

143

Thermoresposi-ve surfaces

Epidermal growth factor (EGF)

Affinity interaction

Heparin-decorated thermoresponsive surfaces facilitated the effective binding of EGF, which enhanced the functions of cultured hepatocytes

Liver disease treatments

47

ECM proteins

VEGF, PDGF TGF-β, FGF

Bioaffinity interaction

ECM would significantly enhance GF capacity to induce wound healing and bone repair

Wound healing舲 and bone regeneration

144

Hyaluronic acid hydrogel

BMP-2

Affinity interaction

BMP-2 immobilized hydrogel promoted formation of ectopic bone with better production of collagen fibers compared to delivering the BMP-2 in non-functionalized hydrogel

Bone regeneration

47

Titanium surfaces

BMP-2

ECM-inspired approach

The ECM-inspired microarchitecture and its immobilized BMP-2 with both cell affinitive and high GF loading capacity synergistically enhance the activity and osteogenetic differentiation of stem cells

Bone regeneration

50

  1. Abbreviation: GFs, growth factors.