Protein-Based Hydrogels and Their Biomedical Applications

Abstract

Hydrogels made from proteins are attractive materials for diverse medical applications, as they are biocompatible, biodegradable, and amenable to chemical and biological modifications. Recent advances in protein engineering, synthetic biology, and material science have enabled the fine-tuning of protein sequences, hydrogel structures, and hydrogel mechanical properties, allowing for a broad range of biomedical applications using protein hydrogels. This article reviews recent progresses on protein hydrogels with special focus on those made of microbially produced proteins. We discuss different hydrogel formation strategies and their associated hydrogel properties. We also review various biomedical applications, categorized by the origin of protein sequences. Lastly, current challenges and future opportunities in engineering protein-based hydrogels are discussed. We hope this review will inspire new ideas in material innovation, leading to advanced protein hydrogels with desirable properties for a wide range of biomedical applications.

Genetically Engineered Protein-Based Bioadhesives with Programmable Material Properties

“…For instance, even with advanced cross-linking methods or double cross-linking, silk-derived hydrogels exhibited a tensile strength of 10–15 kPa, and gelatin-based hydrogels had tensile strength less than 95 kPa. ,,, In comparison, our 16KLV-2Mfp hydrogel displayed a tensile strength of 3.0 ± 0.3 MPa. Additionally, hydrogels made of naturally derived protein polymers such as chitosan, gelatin, and collagen showed adhesion of less than 100 kPa on wet tissue surfaces. ,,, Similarly, the adhesion of some silk-based hydrogels and mussel-inspired polymers is also lower than 30 kPa. , In comparison, our 16KLV-2Mfp protein hydrogel exhibited an adhesion of 416 ± 20 kPa, substantially higher than those in previous reports.…”

“…Additionally, hydrogels made of naturally derived protein polymers such as chitosan, gelatin, and collagen showed adhesion of less than 100 kPa on wet tissue surfaces. 1,18,52,53 Similarly, the adhesion of some silk-based hydrogels and musselinspired polymers is also lower than 30 kPa. 4,54 In comparison, our 16KLV-2Mfp protein hydrogel exhibited an adhesion of 416 ± 20 kPa, substantially higher than those in previous reports.…”

“…that match the target tissue. Several types of commercial bioglues have been recently developed, including cyanoacrylates, polyester-based adhesives, and poly­(acrylic acid)-based glues. − Most bioglues are synthetic polymers with limited biodegradability, high toxicity, and lack of tunability. − Furthermore, many existing bioglues do not have desirable adhesion to wet biological tissues, thus limiting their practical use. ,, A class of bioglues that has not been extensively explored are those that are completely made of proteins. , Protein-based adhesives are generally biocompatible and bioabsorbable as many protein-based biomaterials have been used for biomedical applications. ,,− Additionally, recombinant proteins synthesized from DNA templates allow their protein sequences to be precisely controlled, enabling fine-tuning of mechanical and adhesive properties to match specific requirements for biomedical applications. ,,, These features are hardly achieved by other materials.…”

Blending recombinant amyloid silk proteins generates composite fibers with tunable mechanical properties

“…7,8 Despite the challenges posed by their repetitive sequences and biased amino acid compositions, recent advances in synthetic biology have overcome many obstacles in the heterologous synthesis of mechanically robust PBMs. [9][10][11] Several microbially produced PBMs have displayed mechanical performances comparable to or even higher than their natural counterparts. [12][13][14][15] While most recombinant PBMs typically comprise a single purified protein-an approach crucial for studying material sequence-structure-property relationships-natural PBMs commonly contain a mixture of different proteins with unique attributes in their amino acid compositions, secondary structures, and molecular weights (MWs).…”

“…7,8 Despite the challenges posed by their repetitive sequences and biased amino acid compositions, recent advances in synthetic biology have overcome many obstacles in the heterologous synthesis of mechanically robust PBMs. 9–11 Several microbially produced PBMs have displayed mechanical performances comparable to or even higher than their natural counterparts. 12–15…”