J. Mater. Sci. Technol. ›› 2020, Vol. 59: 227-233.DOI: 10.1016/j.jmst.2020.03.074
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Xiao Lina, Yanjie Baib, Huan Zhouc, Lei Yanga,c,*()
Received:
2020-01-05
Revised:
2020-03-02
Accepted:
2020-03-03
Published:
2020-12-15
Online:
2020-12-18
Contact:
Lei Yang
Xiao Lin, Yanjie Bai, Huan Zhou, Lei Yang. Mechano-active biomaterials for tissue repair and regeneration[J]. J. Mater. Sci. Technol., 2020, 59: 227-233.
Fig. 1. Schematic illustration of the rationale and mechanisms of mechano-active biomaterials for tissue repair and regeneration. (a) Mechano-active biomaterials can dynamically utilize the mechanical stimuli to realize the spatially-temporally controlled release or the targeted delivery of molecules/cells (M/C) for tissue repair and regeneration. The main mechanisms include: (i) compression/tension-induced deformation of the bulk carriers, (ii) temporary loss of the hydrogel structure by rupturing the physical crosslinks, (iii) disintegration of the aggregates of nanoparticles with drugs into nanoscale components, (iv) deformation and disintegration of the drug-loaded vesicles. (b) Reconstruction of the mechanical environment at the tissue-level that are beneficial for tissue repair and regeneration. (c) Biomimetic mechano-active biomaterials can accommodate or utilize important mechanical cues to accelerate tissue remodeling or healing process via a mechanobiological effect.
Material systems | Mechanisms | Cargo release behavior | Potential applications | Ref. |
---|---|---|---|---|
Hyaluronic hydrogel covalently integrated with dexamethasone (DEX)-loaded block copolymer micelles (BCMs) | A force-induced reversible deformation of BCMs and the penetration of water into BCMs. | DEX release is controlled in a strain-dependent manner by external compression | Treatment of osteoarthritis-like symptoms with intra-articular hydrogel injections | [ |
Hydrogel physically and chemically attached with cargo-filled mechano-sensitive liposomes | Proper level of mechanical force applied to the hydrogel ruptures the liposomes and releases the cargo | Release increases with the increasing force (within 200 cycles, 0.016 % cargo release per cycle for 10 % strain and 0.034 % for 25 % strain, respectively) | A long-term intra-articular drug release | [ |
Polyacrylamide (PAAm) with pyrene-loaded BCMs | Stretch-induced reversible micelle deformation leads to a dynamic release of pyrene | In the presence of the selected stretching regimen, the amount of pyrene released during each stretch period at 60% strain was approximately two times higher than that at 30% strain, and 2.5 times higher than that by the static controls | Precise release of drug and therapeutic agents for tissue repair or regeneration | [ |
A highly stretchable elastomer imbedded with alginate microgels containing drug-encapsulated polymeric nanoparticles | The deformation of the enlarged surface area of microdepot under stretching of elastomer substrate facilitates the drug release | Tensile strain can effectively stimulate the release of DOX, with an increase in the release amount at a higher strain. An interval of 4 h was sufficient for the drug to “recharge” in the microdepots | ? Skin-mountable device for treating skin diseases ? Delivery of drugs to the body through transcutaneous administration ? Integrated with | [ |
Highly textured superhydrophobic electrosprayed microparticle coatings with a cellulose/polyester core | Stretching induces formation of periodic parallel cracks in coating, leading to more exposure of the core surface to water | The release of entrapped cisplatin and 7-ethyl-10-hydroxycamptothecin was controlled by the magnitude of applied strain. Strain-dependent release rates depended on the lipophilicity of the drugs | Drug delivery applications to the tissue where periodic mechanical forces are generated | [ |
A drug-loaded polyurethane layer coated with a titanium layer | Under tensile strain, micro-sized cracks are generated and propagated in the titanium layer, acting as a channel for the drug molecules to diffuse into the surroundings | The amount of released drug increases with the applied strain. The drug release profile has a highly linear correlation with the ‘ratio of the exposed region under strain’ | Drug-releasing or -eluting stents. Self-administered drug delivery system for patients in emergency | [ |
Ceramic composite sponge (CCS) | The resilient nature and hierarchical pore structure allow liquids to flow in and out of CCS under cyclic compressive strains. Water content and strain are two logic control gates of release. | Achieved precise and logical release of both hydrophobic and hydrophilic molecules (about 100 nanogram/cycle) and fibroblasts (about 1400 cells/cycle) in proportion to the strains | Tissue engineering scaffold for bone, cartilage, blood vessel, muscle and myocardium repair by precise release of drugs or cells | [ |
Amide-bearing 1,3-dipalmitami dopropan-2-yl 2-(trimethylammonio)ethyl phosphate (Pad-PC-Pad) phospholipid vesicles | Under fluid shear stress, the lenticular shape of the liposomes leads to preferential breaking points along the vesicle’s equator | Pad-PC-Pad vesicles preferentially release drugs in response to high shear stress | Treating cardiovascular diseases in a targeted manner | [ |
Aggregates of multiple nanoparticles (NPs) immobilized with the tissue plasminogen activator | Microscale aggregates of nanoparticles break up into nanoscale components when exposed to abnormally high fluid shear stress | Pathological levels of shear caused large increase in the disintegration of the microscale aggregates into NPs compared to the physiological levels of shear | Thrombolytic therapies with high safety for administration of clot-busting drugs to patients with life-threatening clots | [ |
Table 1 Examples of mechano-active biomaterials for precisely controlled delivery.
Material systems | Mechanisms | Cargo release behavior | Potential applications | Ref. |
---|---|---|---|---|
Hyaluronic hydrogel covalently integrated with dexamethasone (DEX)-loaded block copolymer micelles (BCMs) | A force-induced reversible deformation of BCMs and the penetration of water into BCMs. | DEX release is controlled in a strain-dependent manner by external compression | Treatment of osteoarthritis-like symptoms with intra-articular hydrogel injections | [ |
Hydrogel physically and chemically attached with cargo-filled mechano-sensitive liposomes | Proper level of mechanical force applied to the hydrogel ruptures the liposomes and releases the cargo | Release increases with the increasing force (within 200 cycles, 0.016 % cargo release per cycle for 10 % strain and 0.034 % for 25 % strain, respectively) | A long-term intra-articular drug release | [ |
Polyacrylamide (PAAm) with pyrene-loaded BCMs | Stretch-induced reversible micelle deformation leads to a dynamic release of pyrene | In the presence of the selected stretching regimen, the amount of pyrene released during each stretch period at 60% strain was approximately two times higher than that at 30% strain, and 2.5 times higher than that by the static controls | Precise release of drug and therapeutic agents for tissue repair or regeneration | [ |
A highly stretchable elastomer imbedded with alginate microgels containing drug-encapsulated polymeric nanoparticles | The deformation of the enlarged surface area of microdepot under stretching of elastomer substrate facilitates the drug release | Tensile strain can effectively stimulate the release of DOX, with an increase in the release amount at a higher strain. An interval of 4 h was sufficient for the drug to “recharge” in the microdepots | ? Skin-mountable device for treating skin diseases ? Delivery of drugs to the body through transcutaneous administration ? Integrated with | [ |
Highly textured superhydrophobic electrosprayed microparticle coatings with a cellulose/polyester core | Stretching induces formation of periodic parallel cracks in coating, leading to more exposure of the core surface to water | The release of entrapped cisplatin and 7-ethyl-10-hydroxycamptothecin was controlled by the magnitude of applied strain. Strain-dependent release rates depended on the lipophilicity of the drugs | Drug delivery applications to the tissue where periodic mechanical forces are generated | [ |
A drug-loaded polyurethane layer coated with a titanium layer | Under tensile strain, micro-sized cracks are generated and propagated in the titanium layer, acting as a channel for the drug molecules to diffuse into the surroundings | The amount of released drug increases with the applied strain. The drug release profile has a highly linear correlation with the ‘ratio of the exposed region under strain’ | Drug-releasing or -eluting stents. Self-administered drug delivery system for patients in emergency | [ |
Ceramic composite sponge (CCS) | The resilient nature and hierarchical pore structure allow liquids to flow in and out of CCS under cyclic compressive strains. Water content and strain are two logic control gates of release. | Achieved precise and logical release of both hydrophobic and hydrophilic molecules (about 100 nanogram/cycle) and fibroblasts (about 1400 cells/cycle) in proportion to the strains | Tissue engineering scaffold for bone, cartilage, blood vessel, muscle and myocardium repair by precise release of drugs or cells | [ |
Amide-bearing 1,3-dipalmitami dopropan-2-yl 2-(trimethylammonio)ethyl phosphate (Pad-PC-Pad) phospholipid vesicles | Under fluid shear stress, the lenticular shape of the liposomes leads to preferential breaking points along the vesicle’s equator | Pad-PC-Pad vesicles preferentially release drugs in response to high shear stress | Treating cardiovascular diseases in a targeted manner | [ |
Aggregates of multiple nanoparticles (NPs) immobilized with the tissue plasminogen activator | Microscale aggregates of nanoparticles break up into nanoscale components when exposed to abnormally high fluid shear stress | Pathological levels of shear caused large increase in the disintegration of the microscale aggregates into NPs compared to the physiological levels of shear | Thrombolytic therapies with high safety for administration of clot-busting drugs to patients with life-threatening clots | [ |
Fig. 2. Strain-sensitive mechano-active drug delivery systems. (a) Hyaluronic acid hydrogels with a compression-modulated dexamethasone release capacity (reprinted with permission from [23]); (b) A hydrogel trapped with drug-loaded liposomes, which releases drugs through the rupture of the liposomes under proper level of stress (reprinted with permission from [24]); (c) Stretching-triggered drug release from the nanoparticles into microdepots on an elastomeric substrate (reprinted with permission from [26]); (d) Crack development in the superhydrophobic barrier coating on a hydrophilic mesh core when stretched (reprinted with permission from [27]); (e) A ceramic-starch composite sponge (CCS) with a hierarchically porous structure, demonstrating a mechano-active delivery of molecules and cells with high precision (reprinted with permission from [30]).
Fig. 3. Shear-sensitive mechano-active drug delivery systems. (a) Shear-sensitive lenticular vesicles made from an artificial 1,3-diaminophospholipid which are stable under static conditions but release their contents at elevated shear stress via preferential breaking points along the vesicle’s equator (reprinted with permission from [32]). (b) Microaggregates of nanoparticles (large spheres) remain intact in the pre-stenotic region, but then disintegrate into nanoparticles (small spheres) when they flow through a constriction and accumulate in the endothelial cells (reprinted with permission from [33]); (c) A hydrogel with a shear-mediated release of anti-TNFα (reprinted with permission from [35]).
Fig. 4. A finite-element simulation optimized gel-point adhesive starch hydrogel as a mechano-active epicardial patch for treating a myocardial infarction [44]. (a) Illustration of the finite-element simulation model for the epicardial patch; (b) Effect of viscous dissipation with a Maxwell viscoelastic patch on stroke volume, pointing the optimized effect when having G"/G′ ratio ~ 1; (c) Dependence of G′, G′′ and the G"/G′ ratio of the gel-point adhesive epicardial patch (GPAP) on the frequency of oscillation, showing a gel-point viscoelastic characteristic. The GPAP not only accommodates the cyclic deformation of the myocardium but also actively interacted with it to reconstruct normal mechanical environment. Inset shows a stretched GPAP film adhering firmly on a pig epicardium; (d) GPAP significantly decreased the left ventricular relaxation time constant, indicating markedly improved biomechanical function of the left ventricle when the GPAP was applied after a myocardial infarction. (a, b, c and d reprinted with permission from [44]).
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