Microfabrication of a biomimetic arcade-like electrospun scaffold for cartilage tissue engineering applications.

In recent years, the engineering of biomimetic cellular microenvironments has emerged as a top priority for regenerative medicine, being the in vitro recreation of the arcade-like cartilaginous tissue one of the most critical challenges due to the notorious absence of cost- and time-efficient microfabrication techniques capable of building 3D fibrous scaffolds with precise anisotropic properties. Taking this into account, we suggest a feasible and accurate methodology that uses a sequential adaptation of an electrospinning-electrospraying set up to construct a hierarchical system comprising both polycaprolactone (PCL) fibres and polyethylene glycol sacrificial microparticles. After porogen leaching, the bi-layered PCL scaffold was capable of presenting not only a depth-dependent fibre orientation similar to natural cartilage, but also mechanical features and porosity proficient to encourage an enhanced cell response. In fact, cell viability studies confirmed the biocompatibility of the scaffold and its ability to guarantee suitable cell adhesion, proliferation and migration throughout the 3D anisotropic fibrous network during 21 days of culture. Additionally, likewise the hierarchical relationship between chondrocytes and their extracellular matrix, the reported PCL scaffold was able to induce depth-dependent cell-material interactions responsible for promoting a spatial modulation of the morphology, alignment and density of the cells in vitro.

Natural-Based Hydrogels for Tissue Engineering Applications.

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.

Mesenchymal Stem Cell Capping on ECM-Anchored Caspase Inhibitor-Loaded PLGA Microspheres for Intraperitoneal Injection in DSS-Induced Murine Colitis.

Mesenchymal stem cells (MSCs) are considered as a promising alternative for the treatment of various inflammatory disorders. However, poor viability and engraftment of MSCs after transplantation are major hurdles in mesenchymal stem cell therapy. Extracellular matrix (ECM)-coated scaffolds provide better cell attachment and mechanical support for MSCs after transplantation. A single-step method for ECM functionalization on poly(lactic-co-glycolic acid) (PLGA) microspheres using a novel compound, dopamine-conjugated poly(ethylene-alt-maleic acid), as a stabilizer during the preparation of microspheres is reported. The dopamine molecules on the surface of microspheres provide active sites for the conjugation of ECM in an aqueous solution. The results reveal that the viability of MSCs improves when they are coated over the ECM-functionalized PLGA microspheres (eMs). In addition, the incorporation of a broad-spectrum caspase inhibitor (IDN6556) into the eMs synergistically increases the viability of MSCs under in vitro conditions. Intraperitoneal injection of the MSC-microsphere hybrid alleviates experimental colitis in a murine model via inhibiting Th1 and Th17 differentiation of CD4+ T cells in colon-draining mesenteric lymph nodes. Therefore, drug-loaded ECM-coated surfaces may be considered as attractive tools for improving viability, proliferation, and functionality of MSCs following transplantation.

Recent Advances in Biodegradable Conducting Polymers and Their Biomedical Applications.

The growing importance of biodegradable conducting polymers (CPs) have fueled the rapid development of this unique class of polymeric materials in recent years. Possessing both the electrical conductivity approaching those of metallic conductors and the biodegradability of biocompatible polymers, biodegradable CPs are highly sought after. In fact, they have emerged as the ideal biomaterials, having immense potential for augmenting a wide range of practical biomedical applications. Herein, we provide a broad overview of recent advances in the development of biodegradable CPs and their biomedical applications. We first introduce the fundamentals of conducting and biodegradable polymers, followed by discussions on the major strategies currently used to fabricate biodegradable CPs. We then highlight the potential biomedical applications of biodegradable CPs (specifically those for tissue engineering, regenerative medicine, and biomedical imaging as well as biomedical implants, bioelectronics devices, and consumer electronics). We conclude this review by offering our perspectives on the current challenges and future opportunities facing the development and practical applications of biodegradable CPs.

DNA polymeric films as a support for cell growth as a new material for regenerative medicine: Compatibility and applicability.

DNA polymeric films (DNA-PFs) are a promising drug delivery system (DDS) in modern medicine. In this study, we evaluated the growth behavior of oral squamous cell carcinoma (OSCC) cells on DNA-PFs. The morphological, biochemical, and cytometric features of OSCC cell adhesion on DNA-PFs were also assessed. An initial, temporary alteration in cell morphology was observed at early time points owing to the inhibition of cell attachment to the film, which then returned to a normal morphological state at later time points. MTT and resazurin assays showed a moderate reduction in cell viability related to increased DNA concentration in the DNA-PFs. Flow cytometry studies showed low cytotoxicity of DNA-PFs, with cell viabilities higher than 90% in all the DNA-PFs tested. Flow cytometric cell cycle analysis also showed average cell cycle phase distributions at later time points, indicating that OSCC cell growth is maintained in the presence of DNA-PFs. These results show high biocompatibility of DNA-PFs and suggest their use in designing "dressing material," where the DNA film acts as a support for cell growth, or with incorporation of active or photoactive compounds, which can induce tissue regeneration and are useful to treat many diseases, especially oral cancer.

An oxygen plasma treated poly(dimethylsiloxane) bioscaffold coated with polydopamine for stem cell therapy.

In this study, 3D macroporous bioscaffolds were developed from poly(dimethylsiloxane) (PDMS) which is inert, biocompatible, non-biodegradable, retrievable and easily manufactured at low cost. PDMS bioscaffolds were synthesized using a solvent casting and particulate leaching (SCPL) technique and exhibited a macroporous interconnected architecture with 86 ± 3% porosity and 300 ± 100 µm pore size. As PDMS intrinsically has a hydrophobic surface, mainly due to the existence of methyl groups, its surface was modified by oxygen plasma treatment which, in turn, enabled us to apply a novel polydopamine coating onto the surface of the bioscaffold. The addition of a polydopamine coating to bioscaffolds was confirmed using composition analysis. Characterization of oxygen plasma treated-PDMS bioscaffolds coated with polydopamine (polydopamine coated-PDMS bioscaffolds) showed the presence of hydroxyl and secondary amines on their surface which resulted in a significant decrease in water contact angle when compared to uncoated-PDMS bioscaffolds (35 ± 3%, P < 0.05). Seeding adipose tissue-derived mesenchymal stem cells (AD-MSCs) into polydopamine coated-PDMS bioscaffolds resulted in cells demonstrating a 70 ± 6% increase in viability and 40 ± 5% increase in proliferation when compared to AD-MSCs seeded into uncoated-PDMS bioscaffolds (P < 0.05). In summary, this two-step method of oxygen plasma treatment followed by polydopamine coating improves the biocompatibility of PDMS bioscaffolds and only requires the use of simple reagents and mild reaction conditions. Hence, our novel polydopamine coated-PDMS bioscaffolds can represent an efficient and low-cost bioscaffold platform to support MSC therapies.

Processing of Materials for Regenerative Medicine Using Supercritical Fluid Technology.

The increase in the world demand of bone and cartilage replacement therapies urges the development of advanced synthetic scaffolds for regenerative purposes, not only providing mechanical support for tissue formation, but also promoting and guiding the tissue growth. Conventional manufacturing techniques have severe restrictions for designing these upgraded scaffolds, namely, regarding the use of organic solvents, shearing forces, and high operating temperatures. In this context, the use of supercritical fluid technology has emerged as an attractive solution to design solvent-free scaffolds and ingredients for scaffolds under mild processing conditions. The state-of-the-art on the technological endeavors for scaffold production using supercritical fluids is presented in this work with a critical review on the key processing parameters as well as the main advantages and limitations of each technique. A special stress is focused on the strategies suitable for the incorporation of bioactive agents (drugs, bioactive glasses, and growth factors) and the in vitro and in vivo performance of supercritical CO2-processed scaffolds.

A novel cell-containing device for regenerative medicine: biodegradable nonwoven filters with peripheral blood cells promote wound healing.

The efficacy of skin regeneration devices consisting of nonwoven filters and peripheral blood cells was investigated for wound healing. We previously found that human peripheral blood cells enhanced their production of growth factors, such as transforming growth factor ß1 (TGF-ß1) and vascular endothelial growth factor, when they were captured on nonwoven filters. Cells on biodegradable filters were expected to serve as a local supply of growth factors and cell sources when they were placed in wounded skin. Nonwoven filters made of biodegradable polylactic acid (PLA) were cut out as 13-mm disks and placed into cell-capturing devices. Mouse peripheral blood was filtered, resulting in PLA filters with mouse peripheral blood cells (m-PBCs) at capture rates of 65.8 ± 5.2%. Then, the filters were attached to full-thickness surgical wounds in a diabetic db/db mouse skin for 14 days as a model of severe chronic wounds. The wound area treated with PLA nonwoven filters with m-PBCs (PLA/B+) was reduced to 8.5 ± 12.2% when compared with day 0, although the non-treated control wounds showed reduction only to 60.6 ± 27.8%. However, the PLA filters without m-PBCs increased the wound area to 162.9 ± 118.7%. By histopathological study, the PLA/B+ groups more effectively accelerated formation of epithelium. The m-PBCs captured on the PLA filters enhanced keratinocyte growth factor (FGF-7) and TGF-ß1 productions in vitro, which may be related to wound healing. This device is useful for regeneration of wounded skin and may be adaptable for another application.

Cellular nanotechnology: making biological interfaces smarter.

Recently, there has been an outburst of research on engineered cell-material interfaces driven by nanotechnology and its tools and techniques. This tutorial review begins by providing a brief introduction to nanostructured materials, followed by an overview of the wealth of nanoscale fabrication and analysis tools available for their development. This background serves as the basis for a discussion of early breakthroughs and recent key developments in the endeavour to develop nanostructured materials as smart interfaces for fundamental cellular studies, tissue engineering and regenerative medicine. The review covers three major aspects of nanostructured interfaces - nanotopographical control, dynamic behaviour and intracellular manipulation and sensing - where efforts are continuously being made to further understand cell function and provide new ways to control cell behaviour. A critical reflection of the current status and future challenges are discussed as a conclusion to the review.

Surface Tension-Assisted Additive Manufacturing of Tubular, Multicomponent Biomaterials.

The fabrication of functional biomaterials for organ replacement and tissue repair remains a major goal of biomedical engineering. Advances in additive manufacturing (AM) technologies and computer-aided design (CAD) are advancing the tools available for the production of these devices. Ideally, these constructs should be matched to the geometry and mechanical properties of the tissue at the needed implant site. To generate geometrically defined and structurally supported multicomponent and cell-laden biomaterials, we have developed a method to integrate hydrogels with 3D-printed lattice scaffolds leveraging surface tension-assisted AM.

Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

Reproducible control of stem cell populations, regardless of their original source, is required for the true potential of these cells to be realised as medical therapies, cell biology research tools and in vitro assays. To date there is a lack of consistency in successful output when these cells are used in clinical trials and even simple in vitro experiments, due to cell and material variability. The successful combination of single chemistries in nanoarray format to control stem cell, or any cellular behaviour has not been previously reported. Here we report how homogenously nanopatterned chemically modified surfaces can be used to initiate a directed cellular response, particularly mesenchymal stem cell (MSC) differentiation, in a highly reproducible manner without the need for exogenous biological factors and heavily supplemented cell media. Successful acquisition of these data should lead to the optimisation of cell selective properties of materials, further enhancing the role of nanopatterned substrates in cell biology and regenerative medicine. The successful design and comparison of homogenously molecularly nanopatterned surfaces and their direct effect on human MSC adhesion and differentiation are reported in this paper. Planar gold surfaces were patterned by dip pen nanolithography (DPN) to produce arrays of nanodots with optimised fixed diameter of 70 nanometres separated by defined spacings, ranging from 140 to 1000 nm with terminal functionalities of simple chemistries including carboxyl, amino, methyl and hydroxyl. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and subsequent control of cell phenotype and offer significant potential for the future.

Effects of novel non-thermal atmospheric plasma treatment of titanium on physical and biological improvements and in vivo osseointegration in rats.

Titanium (Ti) has achieved extensive applications due to its excellent biocompatibility and mechanical properties. Plasma can enhance surface hydrophilia of Ti with decreased carbon contamination. The traditional conditions using a single gas plasma was for longer treatment time and more prone to being contaminated. We designed and developed novel and universal apparatus and methods with a special clamping device of non-thermal atmospheric plasma (NTAP) treatment using mixed gas for Ti surface activation. We systematically and quantitatively investigated the effective effects of NTAP-Ti. The surface water contact angle decreased by 100%, the carbon content decreased by 80% and oxygen content increased by 50% in the novel NTAP-Ti surfaces. NTAP treatment accelerated the attachment, spread, proliferation, osteogenic differentiation and mineralization of MC3T3-E1 mouse preosteoblasts in vitro. The percentage of bone-to-implant contact increased by 25-40%, and the osteoclasts and bone resorption were suppressed by 50% in NTAP-Ti in vivo. In conclusion, NTAP-Ti substantially enhanced the physical and biological effects and integration with bone. The novel and universal apparatus and methods with a special clamping device using gas mixtures are promising for implant activation by swiftly and effectively changing the Ti surface to a hydrophilic one to enhance dental and orthopedic applications.

Recent developments in regenerative ophthalmology.

Regenerative medicine (RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology (RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs (e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.

Mechanically strengthened hybrid peptide-polyester hydrogel and potential applications in spinal cord injury repair.

ADA16 peptide hydrogels have been broadly used in tissue engineering due to their good biocompatibility and nanofibrous structure mimicking the native extracellular matrix (ECM). However, the low mechanical strength often fails them as implantable scaffolds. To improve the mechanical stability of the RADA16 peptide hydrogel, a photocrosslinkable diacrylated poly(ϵ-caprolactone)-b-poly(ethylene glycol)-b-poly(ϵ-caprolactone) triblock copolymer (PCECDA) was physically combined with RADA16 peptide pre-modified with cell adhesive Arg-Gly-Asp sequence (RADA16-RGD). Consequently, an interpenetrating network, RADA16-RGD/PCECDA, was formed with highly enhanced mechanical property. The storage modulus (G') of RADA16-RGD/PCECDA (6% w/v, mass ratio mRADA16-RGD/mPCECDA = 1:5) hybrid hydrogel was elevated to ∼2000 Pa, compared to the RADA16-RGD (1% w/v) hydrogel alone (∼700 Pa). Furthermore, this hybrid hydrogel retained the nanofibrous structure from RADA16-RGD peptide, but underwent much slower degradation than RADA16-RGD alone. In vitro, the hybrid hydrogel exhibited excellent cytocompatibility and promoted the differentiation of the seeded neural stem cells. Finally, the RADA16-RGD/PCECDA hydrogel demonstrated capability in reducing cavitation, glial scar formation and inflammation at the lesion sites of hemi-sectioned spinal cord injury model in rats, which holds great potential for application in neural tissue engineering and regenerative medicine.

Recent advances in gelatin-based therapeutics.

INTRODUCTION: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules. AREAS COVERED: The most relevant properties of gelatin as biomaterial are presented together with its main therapeutic applications. The latter includes drug delivery systems, tissue engineering approaches, potential uses as ink for 3D/4D Bioprinting, and its relevance in organ-on-a-chip platforms. EXPERT OPINION: Advances in polymer chemistry, mechanobiology, imaging technologies, and 3D biofabrication techniques have expanded the application of gelatin in multiple biomedical research applications ranging from bone and cartilage tissue engineering, to wound healing and anti-cancer therapy. Here, we highlight the latest advances in gelatin-based approaches within the fields of biomaterial-based drug delivery and tissue engineering together with some of the most relevant challenges and limitations.

A Pyk2 inhibitor incorporated into a PEGDA-gelatin hydrogel promotes osteoblast activity and mineral deposition.

Pyk2 is a non-receptor tyrosine kinase that belongs to the family of focal adhesion kinases. Studies from our laboratory and others demonstrated that mice lacking the Pyk2 gene (Ptk2B) have high bone mass, which was due to increased osteoblast activity, as well as decreased osteoclast activity. It was previously reported that a chemical inhibitor that targets both Pyk2 and its homolog FAK, led to increased bone formation in ovariectomized rats. In the current study, we developed a hydrogel containing poly(ethylene glycol) diacrylate (PEGDA) and gelatin which was curable by visible-light and was suitable for the delivery of small molecules, including a Pyk2-targeted chemical inhibitor. We characterized several critical properties of the hydrogel, including viscosity, gelation time, swelling, degradation, and drug release behavior. We found that a hydrogel composed of PEGDA1000 plus 10% gelatin (P1000:G10) exhibited Bingham fluid behavior that can resist free flowing before in situ polymerization, making it suitable for use as an injectable carrier in open wound applications. The P1000:G10 hydrogel was cytocompatible and displayed a more delayed drug release behavior than other hydrogels we tested. Importantly, the Pyk2-inhibitor-hydrogel retained its inhibitory activity against the Pyk2 tyrosine kinase, and promoted osteoblast activity and mineral deposition in vitro. Overall, our findings suggest that a Pyk2-inhibitor based hydrogel may be suitable for the treatment of craniofacial and appendicular skeletal defects and targeted bone regeneration.

Biomimetic modification of dual porosity poly(2-hydroxyethyl methacrylate) hydrogel scaffolds-porosity and stem cell growth evaluation.

The macroporous synthetic poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels as 3D cellular scaffolds with specific internal morphology, so called dual pore size, were designed and studied. The morphological microstructure of hydrogels was characterized in the gel swollen state and the susceptibility of gels for stem cells was evaluated. The effect of specific chemical groups covalently bound in the hydrogel network by copolymerization on cell adhesion and growth, followed by effect of laminin coating were investigated. The evaluated gels contained either carboxyl groups of the methacrylic acid or quaternary ammonium groups brought by polymerizable ammonium salt or their combinations. The morphology of swollen gel was visualized using the laser scanning confocal microscopy. All hydrogels had very similar porous structures - their matrices contained large pores (up to 102 µm) surrounded with gel walls with small pores (100 µm). The total pore volume in hydrogels swollen in buffer solution ranged between 69 and 86 vol%. Prior to the seeding of the mouse embryonal stem cells, the gels were coated with laminin. The hydrogel with quaternary ammonium groups (with or without laminin) stimulated the cell growth the most. The laminin coating lead to a significant and quaternary ammonium groups. The gel chemical modification influenced also the topology of cell coverage that ranged from individual cell clusters to well dispersed multi cellular structures. Findings in this study point out the laser scanning confocal microscopy as an irreplaceable method for a precise and quick assessment of the hydrogel morphology. In addition, these findings help to optimize the chemical composition of the hydrogel scaffold through the combination of chemical and biological factors leading to intensive cell attachment and proliferation.

Nanofiber-based matrices for rotator cuff regenerative engineering.

The rotator cuff consists of a cuff of soft tissue responsible for rotating the shoulder. Rotator cuff tendon tears are responsible for a significant source of disability and pain in the adult population. Most rotator cuff tendon tears occur at the bone-tendon interface. Tear size, patient age, fatty infiltration of muscle, have a major influence on the rate of retear after surgical repair. The high incidence of retears (up to 94% in some studies) after surgery makes rotator cuff injuries a critical musculoskeletal problem to address. The limitations of current treatments motivate regenerative engineering approaches for rotator cuff regeneration. Various fiber-based matrices are currently being investigated due to their structural similarity with native tendons and their ability to promote regeneration. This review will discuss the current approaches for rotator cuff regeneration, recent advances in fabrication and enhancement of nanofiber-based matrices and the development and use of complex nano/microstructures for rotator cuff regeneration. STATEMENT OF SIGNIFICANCE: Regeneration paradigms for musculoskeletal tissues involving the rotator cuff of the shoulder have received great interest. Novel technologies based on nanomaterials have emerged as possible robust solutions for rotator cuff injury and treatment due to structure/property relationships. The aim of the review submitted is to comprehensively describe and evaluate the development and use of nano-based material technologies for applications to rotator cuff tendon healing and regeneration.

Self-assembling in situ gel based on lyotropic liquid crystals containing VEGF for tissue regeneration.

Current tissue-regenerative biomaterials confront two critical issues: the uncontrollable delivery capacity of vascular endothelial growth factor (VEGF) for adequate vascularization and the poor mechanical properties of the system for tissue regeneration. To overcome these two issues, a self-assembling in situ gel based on lyotropic liquid crystals (LLC) was developed. VEGF-LLC was administrated as a precursor solution that would self-assemble into an in situ gel with well-defined internal inverse bicontinuous cubic phases when exposed to physiological fluid at a defect site. The inverse cubic phase with a 3D bicontinuous water channel enabled a 7-day sustained release of VEGF. The release profile of VEGF-LLC was controlled using octyl glucoside (OG) as a hydration-modulating agent, which could enlarge the water channel, yielding a 2-fold increase in water channel size and a 7-fold increase in VEGF release. For the mechanical properties, the elastic modulus was found to decrease from ∼100 kPa to ∼1.2 kPa, which might be more favorable for angiogenesis. Furthermore, the self-recovery ability of the VEGF-LLC gel was confirmed by quick recovery of the inner network in step-strain measurements. In vitro, VEGF-LLC considerably promoted the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) as compared to free VEGF (p < 0.05). Furthermore, angiogenesis was successfully induced in rats after subcutaneous injection of VEGF-LLC. The self-assembling LLC gel showed satisfactory degradability and mild inflammatory response with little impact on the surrounding tissue. The controllable release profile and unique mechanical properties of VEGF-LLC offer a new approach for tissue regeneration. STATEMENT OF SIGNIFICANCE: The potential clinical use of currently available biomaterials in tissue regeneration is limited by their uncontrollable drug delivery capacity and poor mechanical properties. Herein, a self-assembling in situ gel based on lyotropic liquid crystals (LLC) for induced angiogenesis was developed. The results showed that the addition of octyl glucoside (OG) could change the water channel size of LLC, which enabled the LLC system to release VEGF in a sustained manner and to possess a suitable modulus to favor angiogenesis simultaneously. Moreover, the self-recovery capability allowed the gel to match the deformation of surrounding tissues during body motion to maintain its properties and reduce discomfort. In vivo, angiogenesis was induced by VEGF-LLC 14 days after administering subcutaneous injection. These results highlight the potential of LLC as a promising sustained protein drug delivery system for vascular formation and tissue regeneration.

Incorporation of a silicon-based polymer to PEG-DA templated hydrogel scaffolds for bioactivity and osteoinductivity.

A scaffold that is inherently bioactive, osteoinductive and osteoconductive may guide mesenchymal stem cells (MSCs) to regenerate bone tissue in the absence of exogenous growth factors. Previously, we established that hydrogel scaffolds formed by crosslinking methacrylated star poly(dimethylsiloxane) (PDMSstar-MA) with diacrylated poly(ethylene glycol) (PEG-DA) promote bone bonding by induction of hydroxyapatite formation ("bioactive") and promote MSC lineage progression toward osteoblast-like fate ("osteoinductive"). Herein, we have combined solvent induced phase separation (SIPS) with a fused salt template to create PDMSstar-PEG hydrogel scaffolds with controlled PDMSstar-MA distribution as well as interconnected macropores of a tunable size to allow for subsequent cell seeding and neotissue infiltration ("osteoconductive"). Scaffolds were prepared with PDMSstar-MA of two number average molecular weights (Mns) (2k and 7k) with varying PDMSstar-MA:PEG-DA ratios and template salt sizes. The distribution of PDMSstar-MA within the hydrogels was examined as well as pore size, percent interconnectivity, dynamic and static moduli, hydration, degradation and in vitro bioactivity (i.e. mineralization when exposed to simulated body fluid, SBF). Finally, cell culture with seeded human bone marrow-derived MSCs (hBMSCs) was used to confirm non-cytotoxicity and characterize osteoinductivity. Tunable, interconnected macropores were achieved by utilization of a fused salt template of a specified salt size during fabrication. Distribution of PDMSstar-MA within the PEG-DA matrix improved for the lower Mn and contributed to differences in specific material properties (e.g. local modulus) and cellular response. However, all templated SIPS PDMSstar-PEG hydrogels were confirmed to be bioactive, non-cytotoxic and displayed PDMSstar-MA dose-dependent osteogenesis. STATEMENT OF SIGNIFICANCE: A tissue engineering scaffold that can inherently guide mesenchymal stem cells (MSCs) to regenerate bone tissue without growth factors would be a more cost-effective and safe strategy for bone repair. Typically, glass/ceramic fillers are utilized to achieve this through their ability to induce hydroxyapatite formation ("bioactive") and promote MSC differentiation to an osteoblast-like fate ("osteoinductive"). Herein, we have fabricated an interconnected, macroporous PEG-DA hydrogel scaffold that utilizes PDMSstar-MA as a bioactive and osteoinductive scaffold component. We were able to show that these PDMSstar-PEG hydrogels maintain several key material characteristics for bone repair. Further, bioactivity and osteoinductivity were simultaneously achieved in human bone marrow-derived MSC culture, representing a notable achievement for an exclusively material-based strategy.