Physical Properties Of Hydrogels Research Articles

Effect of bioactive borate glass on printability and physical properties of hydrogels

Hydrogels are a key component in bioinks and biomaterial inks for bioprinting due to their biocompatibility and printability at room temperature. The research described in the present paper contributes to the advancement of bioprinting by studying the effect of bioactive borate glass (BBG) incorporated into hydrogels on printability and physical properties. In this study, we fabricated 3D-printed hydrogel scaffolds using gelatin and alginate hydrogel mixture incorporated with various amounts of BBG, a bioceramic rich in therapeutic ions including boron, calcium, copper, and zinc. We investigated the effect of incorporating BBG on the density, viscosity, physical interactions, chemical structure, and shear thinning behavior of gelatin-alginate hydrogel biomaterial ink at different temperatures. After 3D printing and crosslinking of scaffolds, we measured mechanical properties and printing outcomes. The near-optimal extrusion temperature and pressure for uniform extrusion of hydrogel filaments at various BBG contents were determined. We compared the printing outcomes by quantifying the uniformity of printed filaments and shape fidelity of printed scaffolds. The rheological analysis showed that the addition of BBG increased the viscosity of the biomaterial inks and Young’s modulus of the 3D-printed scaffolds. Biomaterial inks with a dynamic viscosity within the range of 4.5 – 6.5 Pa·s showed the best printability across all samples. In conclusion, the inclusion of BBG contributes to a substantial improvement in the physical properties and printability of 3D-printed gelatin-alginate hydrogels.

Thermo-tunable Injectable Thermosensitive Hydrogel and its Application as Protein Carriers

It is known that polymer chemistries determine mechanical and physical properties of hydrogels and thus its drug delivery performance. In order to achieve desired drug release behavior, triblock copolyester PCT-PEG-PCT with proper hydrogel formulation has to be synthesized. This research has demonstrated a way to adjust hydrogel mechanical and gelation properties by simply physically mixing amphiphilic copolymers with different composition to achieve desired protein carriers. Tri-block copolymer poly (CL-co-TOSUO)-PEG-poly (CL-co-TOSUO), briefed as (PCT-PEG-PCT) with different composition have been successfully synthesized. These copolymers are thermosensitive and can form hydrogels in aqueous solution. Copolymers with higher percentage hydrophobic PCT blocks show higher mechanical stiffness and yet lower solubility. To reduce the crystallinity of the hydrophobic block and soften the hydrogel, the copolymer with long PCT blocks was physically mixed with ones with shorter PCT blocks. The polymer mixture demonstrated a moderated mechanical stiffness and desired solubility. The polymer mixture also achieved a gelation temperature at 37°C, which is desirable for drug delivery. Macromolecular drug, bovine serum albumin (BSA) was used as model drug for its release study. This protein drug was successfully loaded into the polymer mixture, and the drug release study shows the polymer mixture is able to extend a stable drug release for over 48 hours. This result confirms physical mixing of PCT-PET-PCT thermosensitive copolymers can tune gel properties and improve drug delivery performance without redesigning and synthesizing new polymers.

Advances in 3D Gel Printing for Enzyme Immobilization.

Incorporating enzymes with three-dimensional (3D) printing is an exciting new field of convergence research that holds infinite potential for creating highly customizable components with diverse and efficient biocatalytic properties. Enzymes, nature’s nanoscale protein-based catalysts, perform crucial functions in biological systems and play increasingly important roles in modern chemical processing methods, cascade reactions, and sensor technologies. Immobilizing enzymes on solid carriers facilitates their recovery and reuse, improves stability and longevity, broadens applicability, and reduces overall processing and chemical conversion costs. Three-dimensional printing offers extraordinary flexibility for creating high-resolution complex structures that enable completely new reactor designs with versatile sub-micron functional features in macroscale objects. Immobilizing enzymes on or in 3D printed structures makes it possible to precisely control their spatial location for the optimal catalytic reaction. Combining the rapid advances in these two technologies is leading to completely new levels of control and precision in fabricating immobilized enzyme catalysts. The goal of this review is to promote further research by providing a critical discussion of 3D printed enzyme immobilization methods encompassing both post-printing immobilization and immobilization by physical entrapment during 3D printing. Especially, 3D printed gel matrix techniques offer mild single-step entrapment mechanisms that produce ideal environments for enzymes with high retention of catalytic function and unparalleled fabrication control. Examples from the literature, comparisons of the benefits and challenges of different combinations of the two technologies, novel approaches employed to enhance printed hydrogel physical properties, and an outlook on future directions are included to provide inspiration and insights for pursuing work in this promising field.

Modulation of spatial and topological inhomogeneities of linear polymer hydrogel

It is well known that physical properties such as optical transparency, mechanical strength and permeability of hydrogel are strongly related to inhomogeneities of hydrogel. The physical properties of hydrogel, including inhomogeneity, are affected by the polymer volume fraction and amount of crosslinker at the state of hydrogel preparation typically. To study the influence of polymer volume fraction and amount of crosslinker on the inhomogeneities of linear polymer hydrogel, molecular dynamics simulation is performed to reproduce gelation process and quantified inhomogeneities of the obtained hydrogel network. Furthermore, the generation and variation mechanisms of inhomogeneities in linear polymer hydrogel are revealed through investigation of crosslink pattern and formation and collapse of cluster. The results indicate that increase of the polymer volume fraction and decrease of amount of crosslinker can increase the spatial inhomogeneity of the hydrogel. The topological inhomogeneity increases almost monotonically with polymer volume fraction, but first increases and then decreases with the increase of the amount of crosslinker. It is concluded that inhomogeneities of linear polymer hydrogel can be flexibly modulated by polymer volume fraction and amount of crosslinker.

The influence of poly(allylamine hydrochloride) hydrogel crosslinking density on its thermal and phosphate binding properties

Sevelamer hydrochloride (SH) or Renagel® is an effective phosphate binder prescribed to prevent the absorption of phosphate in end stage renal disease (ESRD) patients. The relationship between SH structure and binding capacity and affinity is very important and can be used in characterising the sensitivity of the hydrogel to binding conditions. Thus, a series of hydrogels were prepared by varying the amount of crosslinker, whilst the other hydrogel components were kept constant. Variation of this parameter influenced the hydrogel structure as shown by swelling data, differential scanning calorimetry and solid state nuclear magnetic resonance spectroscopy. The hydrogels’ physical characteristics were found to correlate with the number of phosphate binding sites and affinity obtained from the Langmuir–Freundlich Isotherm (L–FI) and affinity distribution spectra (AD). The hydrogels formed using lower amounts of crosslinker showed a slight increase in binding capacity but with lower affinity. However, the influence of the pH of the binding media on the binding parameters of sevelamer hydrochloride was significant. This is the first report on the use of AD spectra generated from L-FI binding parameters in hydrogels, which demonstrates the sensitivity of the affinity and binding site numbers to changes in hydrogel physical properties and the pH of the binding media.

A Biomimetic Platelet-Rich Plasma-Based Interpenetrating Network Printable Hydrogel for Bone Regeneration.

Repair of bone defects caused by trauma or diseases is the primary focus of prosthodontics. Hydrogels are among the most promising candidates for bone tissue regeneration due to their unique features such as excellent biocompatibility, similarities to biological tissues, and plasticity. Herein, we developed a type of novel biomimetic interpenetrating polymeric network (IPN) hydrogel by combining methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr) through photo-crosslinking. Platelet-rich plasma (PRP), a patient-specific source of autologous growth factors, was incorporated into the hydrogel, and thereafter the hydrogels were biological mineralized by simulated body fluid (SBF). Physical properties of hydrogels were comprehensively characterized. In vitro studies demonstrated that the incorporation of PRP and biomineralization promoted the biocompatibility of hydrogel. Strikingly, the osteogenic bioactivities, including ALP activity, mineralized nodule formation, and expression of osteogenic markers were found substantially enhanced by this biomineralized PRP-hydrogel. Finally, a rabbit model of bone defect was employed to assess in vivo bone regeneration, micro-CT analysis showed that the biomineralized PRP-hydrogels could significantly accelerate bone generation. We believed that this novel biomineralized PRP-incorporated IPN hydrogel could be promising scaffolds for bone tissue regeneration.

Pseudocapacitive Conjugated Polyelectrolyte/2D Electrolyte Hydrogels with Enhanced Physico‐Electrochemical Properties

AbstractConducting polymer hydrogels (CPHs) are an attractive class of materials that synergize the electrical properties of organic semiconductors with the physical properties of hydrogels. Of particular interest is the implementation of CPHs as electrode materials for electrochemical energy storage by taking advantage of redox‐tunable conjugated backbones and the large electroactive surface area. Herein, the use of 2D electrolytes as an effective post‐polymerization additive to enhance the pseudocapacitive performance of CPHs, is demonstrated. By using the self‐doped conjugated polyelectrolyte CPE‐K hydrogel as a model system, improvements in cycling stability, specific capacitance and working voltage window upon addition of the 2D electrolytes, are shown. Furthermore, positively charged 2D electrolytes to be more effective than their negatively charged counterparts are revealed. Rheology measurements and SEM imaging indicate that the 2D electrolytes serve as non‐covalent cross‐linkers that help in forming a mechanically more robust and highly percolated conducting network. These results provide a new and simple to execute post‐polymerization strategy to optimize the electrochemical performance of CPH‐based pseudocapacitors.

SEMI-INTERPENETRATING HYDROGEL SYSTEM BASED ON KATIRA GUM (KG) AND POLYVINYL ALCOHOL: SYNTHESIS AND CHARACTERIZATION

The semi-interpenetrating network (SIPN) based hydrogel was synthesized from katira gum and polyvinyl alcohol in an aqueous medium through cross-linking by glutaraldehyde. The structure and physical properties of hydrogel were assessed by 1H NMR, FTIR, TGA, XRD, and DSC. The morphological properties and surface charge of the preparations were studied by SEM and zeta potential, respectively. FTIR ascertained the formation of ether linkages in SIPN hydrogel and the alterations in the amorphous structure were revealed by XRD analysis. The thermograms also reflected the formation of effective cross-linkages in synthesized hydrogel as revealed by changes in peak positions of glass-transition temperature. Outcomes of the study disclosed that the SIPN hydrogel of katira gum could be synthesized by applying polyvinyl alcohol and glutaraldehyde. The developed SIPN may be potentially applied in drug delivery, tissue engineering, ion exchange, cell proliferation, dye removal, and heavy metal ions removal from wastewater.

A flexible rapid self-assembly scaffold-net DNA hydrogel exhibiting cell mobility control

DNA hydrogels have unique properties, such as specific identifiable molecular structures, programmable self-assembly, and excellent biocompatibility, which have led to increasing researches in the field of nanomaterials and biomedical over the past two decades. However, effective methods to regulate the microstructure of DNA hydrogels still lack, which limits their applications in tissue engineering. By introducing DNA scaffolds into rolling circle amplification (RCA) products and implementing rapid self-assembly strategy, we can produce a regulable new type scaffold-net DNA hydrogel in a short time. Scaffolds concentration and RCA time can regulate the microcharacteristics and physical properties of hydrogels. Scaffold-net DNA hydrogels will be a promising bionic platform for the studies of cancer cell metastatic and microenvironment biophysics.

Hydrogels derived from acellular porcine corneal stroma enhance corneal wound healing

Acellular cornea derived hydrogels provide significant advantages in preserving native corneal stromal keratocyte cells and endothelial cells. However, for clinical application, hydrogel physical properties need to be improved, and their role in corneal epithelial wound healing requires further investigation. In this study, an acellular porcine corneal stroma (APCS) hydrogel (APCS-gel) was successfully prepared from 20 mg/ml APCS, demonstrated optimal light transmittance and gelation kinetic properties and retained critical corneal ECM of collagens and growth factors. Compared with fibrin gel, the APCS-gel had a higher porosity ratio and faster nutrition diffusion with an accompanying improvement in the proliferation of primary rabbit corneal epithelial cells (RCECs) and stromal cells (RCSCs). These corneal cell types also displayed improved viability and cellular infiltration. Furthermore, the APCS-gel provides significant advantages in the preservation of RCECs stemness and enhancement of corneal wound healing in vitro and in vivo. After 7 days of culture, 3-4 layers of RCECs were formed on the APCS-gel in vitro, while only 1-2 layers were found on the fibrin gel. More corneal stem/progenitor cell phenotypes (K12-, p63+, ABCG2+) and proliferation phenotypes (Ki67+) were detected on the APCS-gel than fibrin gel. Using a corneal epithelial wound healing model, we also found faster reepithelization in corneas that received APCS-gel compared to fibrin gel. Additionally, our APCS-gel demonstrated better physical and biological properties when compared to Tisseel, a clinically used type of fibrin gel. In conclusion, our APCS-gel provided better corneal epithelial and stromal cell biocompatibility to fibrin gels and due to its transparency and faster gelation time could potentially be superior for clinical purposes. Statement of significanceExtracellular matrix (ECM) can be used to provide tissue specific physical microstructure and biochemical cues for tissue regeneration. Here, we produced an ECM hydrogel derived from acellular porcine cornea stroma (APCS-gel) that retained critical biological characteristics of the native tissue and provided significant transparency and fast gelation time. Our data demonstrated that the APCS-gel was superior to clinically used fibrin gel, as the APCS-gel showed high porosity and permeability, better corneal stromal keratocytes infiltration, increased cellular proliferation and retention of corneal epithelial cells stemness. The APCS-gel improved corneal wound healing in vitro and in vivo. This APCS-gel may have clinical utility for corneal diseases, and the more general approach used to make this hydrogel might be used in other tissues.

Modulation of injectable hydrogel properties for slow co-delivery of influenza subunit vaccine components enhance the potency of humoral immunity.

Vaccines are critical for combating infectious diseases across the globe. Influenza, for example, kills roughly 500,000 people annually worldwide, despite annual vaccination campaigns. Efficacious vaccines must elicit a robust and durable antibody response, and poor efficacy often arises from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system's natural response to extended pathogen exposure during infection by designing an easily administered slow‐delivery influenza vaccine platform. We utilized an injectable and self‐healing polymer‐nanoparticle (PNP) hydrogel platform to prolong the co‐delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique dynamic physical characteristics whereby physicochemically distinct influenza hemagglutinin antigen and a toll‐like receptor 7/8 agonist adjuvant could be co‐delivered over prolonged timeframes that were tunable through simple alteration of the gel formulation. We show a relationship between hydrogel physical properties and the resulting immune response to immunization. When administered in mice, hydrogel‐based vaccines demonstrated enhancements in the magnitude and duration of humoral immune responses compared to alum, a widely used clinical adjuvant system. We found stiffer hydrogel formulations exhibited slower release and resulted in the greatest improvements to the antibody response while also enabling significant adjuvant dose sparing. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of influenza subunit vaccines.

Hydroxy-tyrosol as a Free Radical Scavenging Molecule in Polymeric Hydrogels Subjected to Gamma-Ray Irradiation

Biomedical engineering is employing hydrogels with increasingly exciting possibilities for the treatment and regeneration of pathologically altered, degenerated, or traumatized tissues. Still, the sterilization processes may undesirably change the chemical and physical properties of hydrogels through cross-linking reactions. This work aims to characterize a new method of producing polyethylene oxide (PEO) hydrogels exploiting hydroxy-tyrosol (HT), an anti-oxidant molecule derived from olive leaf and olive oil, as a free radical scavenger to either prevent or limit gamma-ray-induced cross-linking. For this purpose, we produced hydrogels with PEO with two different buffer solutions (phosphate and citrate), varying HT concentration. We analyzed hydrogel preparations before and after gamma-ray irradiation, assessing the viscosity through rheological analysis and the chemical changes through IR analysis. We performed high-performance liquid chromatography (HPLC) analysis to measure residual HT in hydrogels after irradiation. The obtained results show that radiation-induced cross-linking and increase in viscosity of PEO hydrogels can be prevented by tailoring the concentration of HT as a free radical scavenging agent. Irradiation only consumes small amounts of HT; its presence in polymeric hydrogels can significantly impact biomedical applications by its anti-oxidant and anti-microbial activities.

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships.

Hydrogel physical properties are tuned by altering synthesis conditions such as initial polymer concentration and polymer-cross-linker stoichiometric ratios. Traditionally, differences in hydrogel synthesis schemes, such as end-linked poly(ethylene glycol) diacrylate hydrogels and cross-linked poly(vinyl alcohol) hydrogels, limit structural comparison between hydrogels. In this study, we use generalized synthesis variables for hydrogels that emphasize how changes in formulation affect the resulting network structure. We identify two independent linear correlations between these synthesis variables and swelling behavior. Analysis through recently updated swollen polymer network models suggests that synthesis-swelling correlations can be used to make a priori predictions of the stiffness and solute diffusivity characteristics of synthetic hydrogels. The same experiments and analyses performed on methacrylamide-modified gelatin hydrogels demonstrate that complex biopolymer structures disrupt the linear synthesis-swelling correlations. These studies provide insight into the control of hydrogel physical properties through structural design and can be used to implement and optimize biomedically relevant hydrogels.

Hydrogels for Large-Scale Expansion of Stem Cells

Stem cells show great promise for various pre-clinical and clinical applications, including drug screening, disease treatments, and regenerative medicine. In these applications, producing high-quality and large amount of stem cells is highly demanded. Despite challenging, with the development of hydrogel-based cell culture technology, tremendous progress has been made in stem cell expansion and directed differentiation. Hydrogels are soft materials with abundant water. Many hydrogel properties, including biodegradability, mechanical strength, and porosity have been shown to play essential roles in regulating stem cell proliferation and differentiation. The biochemical and physical properties of hydrogels can be specially tailored to mimic the native microenvironment that various stem cells reside in in vivo. A few hydrogel-based systems have been developed for successful stem cell culture and expansion in vitro. In this review, we summarize various types of hydrogels that have been designed to effectively enhance the proliferation of hematopoietic stem cells (HSCs), mesenchymal stem/stromal cells (MSCs), and pluripotent stem cells (PSCs), respectively. According to each stem cell type's preference, we also discuss the strategies for fabricating hydrogels of biochemical and mechanical cues and other characters representing the stem cells’ in vivo microenvironment.

Injectable nanofibrillar hydrogels based on charge-complementary peptide co-assemblies.

Injectable hydrogels are attractive for therapeutic delivery because they can be locally administered through minimally-invasive routes. Charge-complementary peptide nanofibers provide hydrogels that are suitable for encapsulation of biotherapeutics, such as cells and proteins, because they assemble under physiological temperature, pH, and ionic strength. However, relationships between the sequences of charge-complementary peptides and the physical properties of the hydrogels that they form are not well understood. Here we show that hydrogel viscoelasticity, pore size, and pore structure depend on the pairing of charge-complementary "CATCH(+/-)" peptides. Oscillatory rheology demonstrated that co-assemblies of CATCH(4+/4-), CATCH(4+/6-), CATCH(6+/4-), and CATCH(6+/6-) formed viscoelastic gels that can recover after high-shear and high-strain disruption, although the extent of recovery depends on the peptide pairing. Cryogenic scanning electron microscopy demonstrated that hydrogel pore size and pore wall also depend on peptide pairing, and that these properties change to different extents after injection. In contrast, no obvious correlation was observed between nanofiber charge state, measured with ζ-potential, and hydrogel physical properties. CATCH(4+/6-) hydrogels injected into the subcutaneous space elicited weak, transient inflammation whereas CATCH(6+/4-) hydrogels induced stronger inflammation. No antibodies were raised against the CATCH(4+) or CATCH(6-) peptides following multiple challenges in vehicle or when co-administered with an adjuvant. These results demonstrate that CATCH(+/-) peptides form biocompatible injectable hydrogels with viscoelastic properties that can be tuned by varying peptide sequence, establishing their potential as carriers for localized delivery of therapeutic cargoes.

Activated hyaluronic acid/collagen composite hydrogel with tunable physical properties and improved biological properties

Self-crosslinkable and injectable hydrogels were fabricated with collagen type I (Col I) and N-hydroxy sulfosuccinimide activated hyaluronic acid (HA-sNHS) at physiological conditions without any initiators or crosslinkers. The physical properties of hydrogels, such as gelation time, swelling property, degradation property and mechanical property could be regulated by adjusting the substitution degree (DS) of HA-sNHS. Chondrocytes were encapsulated into hydrogels and their proliferation, phenotype maintenance and matrix secretion were characterized. The results demonstrated that chondrocytes in hydrogel Col I/HA-sNHS32% in which the DS of HA-sNHS was 32% secreted more cartilage specific matrix than others. The results of animal experiment demonstrated that hydrogels Col I and Col I/HA-sNHS32% both had good biodegradability and cytocompatibility. This study provided a novel and simple method for fabrication of self-crosslinkable and injectable hydrogels with tunable physical properties. It implied that these hydrogels could find some applications in the fields of cell encapsulation and tissue engineering.

Visible Light-Curable Hydrogel Systems for Tissue Engineering and Drug Delivery.

Visible light-curable hydrogels have been investigated as tissue engineering scaffolds and drug delivery carriers due to their physicochemical and biological properties such as porosity, reservoirs for drugs/growth factors, and similarity to living tissue. The physical properties of hydrogels used in biomedical applications can be controlled by polymer concentration, cross-linking density, and light irradiation time. The aim of this review chapter is to outline the results of previous research on visible light-curable hydrogel systems. In the first section, we will introduce photo-initiators and mechanisms for visible light curing. In the next section, hydrogel applications as drug delivery carriers will be emphasized. Finally, cellular interactions and applications in tissue engineering will be discussed.

Chitosan/Dextran Hydrogel Constructs Containing Strontium-Doped Hydroxyapatite with Enhanced Osteogenic Potential in Rat Cranium.

It is an effective way in bone tissue engineering to promote the mechanical and osteogenic capability of hydrogels by encapsulating mineral particles into polymer matrix. In this work, we reported novel kinds of nanocomposite scaffolds based on hydroxypropyl chitosan/aldehyde dextran hydrogel (CDH) and strontium-nanohydroxyapatite (Sr-nHA) nanoparticles. The molar ratios of Sr/(Sr + Ca) at 0% (nHA), 50% (Sr50nHA), and 100% (Sr100nHA) were fabricated and subsequently incorporated into CDH. The characterization of Sr-nHA/CDH constructs and CDH alone was studied by Fourier transform infrared analysis, X-ray powder diffraction detection, and scanning electron microscopy. The physical properties of hydrogels were further detected by swelling studies, degradation behavior, rheological measurements, mechanical testing, and ion-release behavior. Cell biocompatibility on the scaffolds was determined in vitro, and bone formation in vivo was examined by a rat calvarium defect model. The results showed that either nHA or Sr-nHA nanoparticles incorporation into CDH would significantly improve the rheological and mechanical properties (P < 0.05). The Sr2+ released from the Sr100nHA/CDH was in the range of optimal concentration for pro-osteogenesis. The addition of Sr-nHA significantly enhanced the cell proliferation and osteogenic differentiation of osteoblasts (P < 0.05). The Sr100nHA/CDH exerted the highest promotion on the polarization of macrophages toward the M2 phenotype. The new bone formation of Sr100nHA/CDH was 2.5-fold and 2-fold higher than that of CDH at 4 and 8 weeks, respectively (P < 0.05). HE staining, Masson's trichrome staining, and immunofluorescence staining of OCN results also confirmed that Sr100nHA/CDH had superior bone regeneration compared to other hydrogels in vivo. In conclusion, this novel in situ gelling hydrogel based on injectable and load-bearing 100% Sr-substituted nHA in CDH is expected to have wide orthopedic, dental, and craniofacial applications to enhance bone regeneration.

Precise Construction of Cell-Instructive 3D Microenvironments by Photopatterning a Biodegradable Hydrogel

On the basis of the complexity of the extracellular matrix, it is very important to control the three-dimensional (3D) biochemical and physical properties of hydrogels at the microscale level. In t...

In Vivo Characterization of Poly(ethylene glycol) Hydrogels with Thio-β Esters.

Resorbable hydrogels have numerous potential applications in tissue engineering and drug delivery due to their highly tunable properties and soft tissue-like mechanical properties. The incorporation of esters into the backbone of poly(ethylene glycol) hydrogels has been used to develop libraries of hydrogels with tunable degradation rates. However, these synthetic strategies used to increase degradation rate often result in undesired changes in the hydrogel physical properties such as matrix modulus or swelling. In an effort to decouple degradation rate from other hydrogel properties, we inserted thio-β esters into the poly(ethylene glycol)-diacrylate backbone to introduce labile bonds without changing macromer molecular weight. This allowed the number of hydrolytically labile thio-β esters to be controlled through changing the ratios of this modified macromer to the original macromer without affecting network properties. The retention of hydrogel properties at different macromer ratios was confirmed by measuring gel fraction, swelling ratio, and compressive modulus. The tunable degradation profiles were characterized both in vitro and in vivo. Following confirmation of cytocompatibility after exposure to the hydrogel degradation products, the in vivo host response was evaluated in comparison to medical grade silicone. Collectively, this work demonstrates the utility and tunability of these hydrolytically degradable hydrogels for a wide variety of tissue engineering applications.