Silk‐Based Biomaterials for Cardiac Tissue Engineering

Abstract

Cardiovascular diseases are one of the leading causes of death globally. Among various cardiovascular diseases, myocardial infarction is an important one. Compared with conventional treatments, cardiac tissue engineering provides an alternative to repair and regenerate the injured tissue. Among various types of materials used for tissue engineering applications, silk biomaterials have been increasingly utilized due to their biocompatibility, biological functions, and many favorable physical/chemical properties. Silk biomaterials are often used alone or in combination with other materials in the forms of patches or hydrogels, and serve as promising delivery systems for bioactive compounds in tissue engineering repair scenarios. This review focuses primarily on the promising characteristics of silk biomaterials and their recent advances in cardiac tissue engineering.

Adhesive silk hydrogel patches for localized and sustained delivery of cell-derived nanovesicles

“…Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45,47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

“…To address the challenge of systemic NV delivery, we incorporated NVs into a silk fibroin hydrogel system to control their spatiotemporal delivery directly to heart tissue. Silk fibroin, a natural biopolymer, is gaining traction for cardiovascular applications due to its biocompatibility, tunable porosity and degradation, low-cost, mechanical strength and intrinsic bioactivity, making it well suited to provide structural support to the infarcted myocardium compared to other natural biomaterials [45, 47, 102, 103]. Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo .…”

“…Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo . Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45, 47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

Adhesive silk hydrogel patches for localized and sustained delivery of cell-derived nanovesicles

“…Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45,47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

“…To address the challenge of systemic NV delivery, we incorporated NVs into a silk fibroin hydrogel system to control their spatiotemporal delivery directly to heart tissue. Silk fibroin, a natural biopolymer, is gaining traction for cardiovascular applications due to its biocompatibility, tunable porosity and degradation, low-cost, mechanical strength and intrinsic bioactivity, making it well suited to provide structural support to the infarcted myocardium compared to other natural biomaterials [45, 47, 102, 103]. Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo .…”

“…Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo . Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45, 47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

An Implantable and Degradable Silk Sericin Protein Film Energy Harvester for Next‐Generation Cardiovascular Electronic Devices

“…In the present work, SS was chosen as the base biomaterial due to its excellent biocompatibility, diverse bioactivity, and abundant asymmetric amino acids with adjustable structures. [27,28,32,33,57,58] A biomaterial film based on F-SS was fabricated for the first time using a self-assembly strategy combined with a chemical crosslinking method to demonstrate that SS can exhibit piezoelectric properties through structural adjustments. The developed F-SS/ZnO/PVA-based piezoelectric film showed a high lon-gitudinal piezoelectric tensor d 33 of 12.0 pC N −1 (Figure 3F), surpasses most bio-organic films [13,[41][42][43][44][45] and exceeds those of many polymer-based piezoelectric hydrogels (Table S2, Supporting Information).…”

A Degradable and Biocompatible Supercapacitor Implant Based on Functional Sericin Hydrogel Electrode

“…Herein, silk sericin was selected as the raw biomaterial owing to its excellent biocompatibility along with diverse bioactivities. [24][25][26][27][28] Degradable SrMA/A-rGOhydrogel-based SC was successfully prepared by cross-linking MA-and-A-rGO-comodified sericin sequentially with 4PEGSC and PEGDA, and displayed excellent stability, exceptional electrochemical properties, and biosafety. The remarkable performance was mainly dependent on the utilization of sericin.…”

Adhesive silk hydrogel patches for localized and sustained delivery of cell-derived nanovesicles

“…Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45,47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

“…To address the challenge of systemic NV delivery, we incorporated NVs into a silk fibroin hydrogel system to control their spatiotemporal delivery directly to heart tissue. Silk fibroin, a natural biopolymer, is gaining traction for cardiovascular applications due to its biocompatibility, tunable porosity and degradation, low-cost, mechanical strength and intrinsic bioactivity, making it well suited to provide structural support to the infarcted myocardium compared to other natural biomaterials [45, 47, 102, 103]. Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo .…”

“…Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo . Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45, 47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

An Implantable and Degradable Silk Sericin Protein Film Energy Harvester for Next‐Generation Cardiovascular Electronic Devices

“…In the present work, SS was chosen as the base biomaterial due to its excellent biocompatibility, diverse bioactivity, and abundant asymmetric amino acids with adjustable structures. [27,28,32,33,57,58] A biomaterial film based on F-SS was fabricated for the first time using a self-assembly strategy combined with a chemical crosslinking method to demonstrate that SS can exhibit piezoelectric properties through structural adjustments. The developed F-SS/ZnO/PVA-based piezoelectric film showed a high lon-gitudinal piezoelectric tensor d 33 of 12.0 pC N −1 (Figure 3F), surpasses most bio-organic films [13,[41][42][43][44][45] and exceeds those of many polymer-based piezoelectric hydrogels (Table S2, Supporting Information).…”

A Degradable and Biocompatible Supercapacitor Implant Based on Functional Sericin Hydrogel Electrode

“…Herein, silk sericin was selected as the raw biomaterial owing to its excellent biocompatibility along with diverse bioactivities. [24][25][26][27][28] Degradable SrMA/A-rGOhydrogel-based SC was successfully prepared by cross-linking MA-and-A-rGO-comodified sericin sequentially with 4PEGSC and PEGDA, and displayed excellent stability, exceptional electrochemical properties, and biosafety. The remarkable performance was mainly dependent on the utilization of sericin.…”

Adhesive silk hydrogel patches for localized and sustained delivery of cell-derived nanovesicles

“…Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45,47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

“…To address the challenge of systemic NV delivery, we incorporated NVs into a silk fibroin hydrogel system to control their spatiotemporal delivery directly to heart tissue. Silk fibroin, a natural biopolymer, is gaining traction for cardiovascular applications due to its biocompatibility, tunable porosity and degradation, low-cost, mechanical strength and intrinsic bioactivity, making it well suited to provide structural support to the infarcted myocardium compared to other natural biomaterials [45, 47, 102, 103]. Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo .…”

“…Previous studies have demonstrated the feasibility of combining NVs in decellularized ECM-based [104] and hybrid polyvinyl alcohol/chitosan-based systems (PBA-CP) [105], enabling controlled release of NVs from different hydrogels, while maintaining wound healing capacity in vivo . Unlike ECM-based hydrogels, which often suffer from batch variability and limited tunability, or synthetic hydrogels which are largely biologically inert, silk combines reproducibility, bioactivity, and mechanical strength [45, 47]. Importantly, while previous studies have demonstrated the feasibility of incorporating vesicles into various natural and synthetic biomaterials for cardiac repair, these approaches remain limited by reliance on native EVs with limited scalability and invasiveness of intra-myocardial injection delivery [93].…”

An Implantable and Degradable Silk Sericin Protein Film Energy Harvester for Next‐Generation Cardiovascular Electronic Devices

“…In the present work, SS was chosen as the base biomaterial due to its excellent biocompatibility, diverse bioactivity, and abundant asymmetric amino acids with adjustable structures. [27,28,32,33,57,58] A biomaterial film based on F-SS was fabricated for the first time using a self-assembly strategy combined with a chemical crosslinking method to demonstrate that SS can exhibit piezoelectric properties through structural adjustments. The developed F-SS/ZnO/PVA-based piezoelectric film showed a high lon-gitudinal piezoelectric tensor d 33 of 12.0 pC N −1 (Figure 3F), surpasses most bio-organic films [13,[41][42][43][44][45] and exceeds those of many polymer-based piezoelectric hydrogels (Table S2, Supporting Information).…”

A Degradable and Biocompatible Supercapacitor Implant Based on Functional Sericin Hydrogel Electrode

“…Herein, silk sericin was selected as the raw biomaterial owing to its excellent biocompatibility along with diverse bioactivities. [24][25][26][27][28] Degradable SrMA/A-rGOhydrogel-based SC was successfully prepared by cross-linking MA-and-A-rGO-comodified sericin sequentially with 4PEGSC and PEGDA, and displayed excellent stability, exceptional electrochemical properties, and biosafety. The remarkable performance was mainly dependent on the utilization of sericin.…”