Biomaterials For Tissue Engineering Research Articles

Biomimetically ordered ultralong hydroxyapatite nanowires-based hierarchical hydrogel scaffold with osteoimmunomodulatory and osteogenesis abilities for augmenting bone regeneration

Artificial construction of tissue engineering implants with bone-mimicking structure and osteogenic function is of great significance for bone regeneration, but it remains a formidable challenge. Herein, inspired by natural bone, a biomimetically hierarchical hydrogel scaffold with highly ordered arrangement and multi-layered concentric circular structure is constructed by a convenient free-injection method for osteoimmunomodulation and bone defect regeneration. Ultralong hydroxyapatite nanowires act as skeleton unit to assemble into the hierarchically ordered nanowire bundles and further hybridization with hyaluronic acid methacrylate and loading with layered double hydroxide nanosheets to form the stable biomimetic scaffold. The biomimetic scaffold exhibits anisotropic structure, high water content and porosity, mechanical robustness, and sustained release of bioactive ions. In particular, the excellent biocompatibility together with ordered topography and biochemical cue can guide recruitment and directional migration of stem cells, and effectively promote osteogenic differentiation and vascularization in vitro. Moreover, the biomimetic scaffold induces M2 phenotype polarization of macrophages, thus creating a favorable osteoimmune environment. The in vivo study proves that the biomimetic scaffold can attenuate inflammation, promote vascularized ossification, and further accelerate new bone formation. This study provides an innovative strategy to construct multifunctional anisotropic biomaterials for bone tissue engineering.

Evolution of Hybrid Hydrogels: Next-Generation Biomaterials for Drug Delivery and Tissue Engineering

Hydrogels, being hydrophilic polymer networks capable of absorbing and retaining aqueous fluids, hold significant promise in biomedical applications owing to their high water content, permeability, and structural similarity to the extracellular matrix. Recent chemical advancements have bolstered their versatility, facilitating the integration of the molecules guiding cellular activities and enabling their controlled activation under time constraints. However, conventional synthetic hydrogels suffer from inherent weaknesses such as heterogeneity and network imperfections, which adversely affect their mechanical properties, diffusion rates, and biological activity. In response to these challenges, hybrid hydrogels have emerged, aiming to enhance their strength, drug release efficiency, and therapeutic effectiveness. These hybrid hydrogels, featuring improved formulations, are tailored for controlled drug release and tissue regeneration across both soft and hard tissues. The scientific community has increasingly recognized the versatile characteristics of hybrid hydrogels, particularly in the biomedical sector. This comprehensive review delves into recent advancements in hybrid hydrogel systems, covering the diverse types, modification strategies, and the integration of nano/microstructures. The discussion includes innovative fabrication techniques such as click reactions, 3D printing, and photopatterning alongside the elucidation of the release mechanisms of bioactive molecules. By addressing challenges, the review underscores diverse biomedical applications and envisages a promising future for hybrid hydrogels across various domains in the biomedical field.

Matrix Metalloproteinase-Responsive Hydrogel with On-Demand Release of Phosphatidylserine Promotes Bone Regeneration Through Immunomodulation.

Inflammation-responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)-responsive injectable hydrogel is constructed by integrating an MMP-cleavable peptide (pp) into a covalent tetra-armed poly-(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro-regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG-pp-PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG-pp-PS to transform macrophages into the anti-inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell-free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Advances of Structural Design and Biomedical Applications of Tobacco Mosaic Virus Coat Protein

Recognized as the primary RNA virus to be categorized and extensively studied, the tobacco mosaic virus (TMV) is foundational to advancements in virology, molecular biology, and biomaterials. Over the past few decades, the deep comprehension of the TMV coat protein (TMVcp) molecular structure and assembly principles has stimulated a surge in research on TMVcp structural design using genetic engineering and chemical modification techniques. The unique characteristics of TMVcp, including its nanoscale orderly structure, ease of modification, and considerable drug loading capacity, have enabled significant progress in its biomedical applications. This review summarizes the advanced strategies deployed for TMVcp design and multidimensional assembly and underscores the prototypical applications of TMVcp‐based biomaterials in bioimaging, drug delivery, tissue engineering, and biosensing. Ultimately, the future prospects of TMVcp research in structural design and biomedical applications are explored, which encompass artificial intelligence‐guided structural and functional design, the development of stimulus‐responsive biomaterials, and potential clinical translation.

Generation of Pearl/Calcium Phosphate Composite Particles and Their Integration into Porous Chitosan Scaffolds for Bone Regeneration.

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

Biodegradable Polymers in Veterinary Medicine-A Review.

During the past two decades, tremendous progress has been made in the development of biodegradable polymeric materials for various industrial applications, including human and veterinary medicine. They are promising alternatives to commonly used non-degradable polymers to combat the global plastic waste crisis. Among biodegradable polymers used, or potentially applicable to, veterinary medicine are natural polysaccharides, such as chitin, chitosan, and cellulose as well as various polyesters, including poly(ε-caprolactone), polylactic acid, poly(lactic-co-glycolic acid), and polyhydroxyalkanoates produced by bacteria. They can be used as implants, drug carriers, or biomaterials in tissue engineering and wound management. Their use in veterinary practice depends on their biocompatibility, inertness to living tissue, mechanical resistance, and sorption characteristics. They must be designed specifically to fit their purpose, whether it be: (1) facilitating new tissue growth and allowing for controlled interactions with living cells or cell-growth factors, (2) having mechanical properties that address functionality when applied as implants, or (3) having controlled degradability to deliver drugs to their targeted location when applied as drug-delivery vehicles. This paper aims to present recent developments in the research on biodegradable polymers in veterinary medicine and highlight the challenges and future perspectives in this area.

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.

Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.

The 3D-McMap Guidelines: Three-Dimensional Multicomposite Microsphere Adaptive Printing.

Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure. Utilizing the extrusion printing process, we established a methodology that not only allows the creation of large microsphere scaffolds but also multicomposite matrices into which cells, growth factors, and therapeutics encapsulated in microspheres can be directly deposited during the printing process. Our 3D-McMap method provides some critical guidelines for issues with scaffold shape fidelity during and after printing. Carefully timed breaks, minuscule drying steps, and adjustments to extrusion parameters generated an evenly layered large microsphere scaffold that retained its internal architecture. Such scaffolds are superior to other microsphere-containing scaffolds, as they can release biomolecules in a highly controlled spatiotemporal manner. This capability permits us to study cell responses to the delivered signals to develop scaffolds that precisely modulate new tissue formation.

Electrospun Composite PLLA-PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration.

Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS-based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS-based composite nanofibers poly(l-lactic acid)-poly(polycaprolactone triol-co-sebacic acid-co-N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt) (PLLA-PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS-based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA-PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10-mm rat sciatic nerve defect model show that PLLA-PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA-PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA-PPSB nanomaterial for PNI repair.

DPPH radical scavenging assay: A tool for evaluating antioxidant activity in 3 % cobalt – Doped hydroxyapatite for orthopaedic implants

In the present work, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was used to examine the antioxidant activity of hydroxyapatite (HAP) and of 3 % cobalt doped HAP (Co-HAP). The DPPH assay revealed that 3 % Co-HAP had significant DPPH radical scavenging activity. Co-HAP was synthesised using the sol-gel method, and its characteristics were assessed using energy-dispersive X-ray spectroscopy (EDS), Field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). As the ionic radius of Co is smaller than Ca ion, XRD study reveals that crystallite size reduces from 40.82 nm to 24.91 nm after incorporation of Co into HAP implying substitution of Ca by Co ions. Compared to ascorbic acid, Co-HAP showed exceptional antioxidant potential and, at some doses, even outperformed ascorbic acid in scavenging capability. Notably, the IC50 value for pure HAP was 35, whereas it was substantially lower for Co-HAP at 20.85, indicating that it has stronger antioxidant properties. According to these results, 3 % Co-HAP has much potential for biomedical uses, especially in tissue engineering biomaterials and antioxidant-based therapeutics. Its capacity to prevent diseases brought on by oxidative stress and encourage tissue regeneration makes it a promising option for additional biomedical research.

Bimodal DNA self-origami material with nucleic acid function enhancement

BackgroundThe design of DNA materials with specific nanostructures for biomedical tissue engineering applications remains a challenge. High-dimensional DNA nanomaterials are difficult to prepare and are unstable; moreover, their synthesis relies on heavy metal ions. Herein, we developed a bimodal DNA self-origami material with good biocompatibility and differing functions using a simple synthesis method. We simulated and characterized this material using a combination of oxDNA, freeze–fracture electron microscopy, and atomic force microscopy. Subsequently, we optimized the synthesis procedure to fix the morphology of this material.ResultsUsing molecular dynamics simulation, we found that the bimodal DNA self-origami material exhibited properties of spontaneous stretching and curling and could be fixed in a single morphology via synthesis control. The application of different functional nucleic acids enabled the achievement of various biological functions, and the performance of functional nucleic acids was significantly enhanced in the material. Consequently, leveraging the various functional nucleic acids enhanced by this material will facilitate the attainment of diverse biological functions.ConclusionThe developed design can comprehensively reveal the morphology and dynamics of DNA materials. We thus report a novel strategy for the construction of high-dimensional DNA materials and the application of functional nucleic acid–enhancing materials.Graphical

Synthesis, Characterization and Catechol-Based Bioinspired Adhesive Properties in Wet Medium of Poly(2-Hydroxyethyl Methacrylate-co-Acrylamide) Hydrogels.

Hydrogels consist of crosslinked hydrophilic polymers from which their mechanical properties can be modulated for a wide variety of applications. In the last decade, many catechol-based bioinspired adhesives have been developed following the strategy of incorporating catechol moieties into polymeric backbones. In this work, in order to further investigate the adhesive properties of hydrogels and their potential advantages, several hydrogels based on poly(2-hydroxyethyl methacrylate-co-acrylamide) with N'N-methylene-bisacrylamide (MBA), without/with L-3,4-dihydroxyphenylalanine (DOPA) as a catecholic crosslinker, were prepared via free radical copolymerization. 2-Hydroxyethyl methacrylate (HEMA) and acrylamide (AAm) were used as comonomers and MBA and DOPA both as crosslinking agents at 0.1, 0.3, and 0.5 mol.-%, respectively. The polymeric hydrogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermal analysis and swelling behavior analysis. Subsequently, the mechanical properties of hydrogels were determined. The elastic properties of the hydrogels were quantified using Young's modulus (stress-strain curves). According to the results herein, the hydrogel with a feed monomer ratio of 1:1 at 0.3 mol.-% of MBA and DOPA displayed the highest rigidity and higher failure shear stress (greater adhesive properties). In addition, the fracture lap shear strength of the biomimetic polymeric hydrogel was eight times higher than the initial one (only containing MBA); however at 0.5 mol.-% MBA/DOPA, it was only two times higher. It is understood that when two polymer surfaces are brought into close contact, physical self-bonding (Van der Waals forces) at the interface may occur in an -OH interaction with wet contacting surfaces. The hydrogels with DOPA provided an enhancement in the flexibility compared to unmodified hydrogels, alongside reduced swelling behavior on the biomimetic hydrogels. This approach expands the possible applications of hydrogels as adhesive materials, in wet conditions, within scaffolds that are commonly used as biomaterials in cartilage tissue engineering.

A Review on Silk Fibroin as a Biomaterial in Tissue Engineering

A Review on Silk Fibroin as a Biomaterial in Tissue Engineering

A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration

Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-Ⅰ via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-Ⅰ to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-Ⅰ nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.

Biocompatible Nanocomposites for Postoperative Adhesion: A State-of-the-Art Review.

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Decoupling the roles of mechanical stretching and piezoelectrical stimulation in calcium signal mediated osteogenic differentiation of MSCs on biomimetic nanofibers

Piezoelectric materials implanted in vivo will be affected by physiological stress, leading to the generation of dynamic piezoelectrical signals. The cells identify both piezoelectrical and mechanical stimuli, and the way they behave is regulated through an electromechanical coupling process. Understanding the specific functions of individual stimulation on the osteogenic differentiation of mesenchymal stem cells (MSCs) would aid the development of ideal biomaterials for bone tissue engineering. In this work, by utilizing the controllable piezoelectric properties of polylactic acid materials, we prepared biomimetic piezoelectric poly (L-lactic acid) nanofibers and its non-piezoelectric isomer poly (D, l-lactide) nanofibers using the electrospinning technology. The dynamic piezoelectric and mechanical stimuli on the nanofibers were theoretically and experimentally investigated. A home-made in-situ mechanical loading platform was used to apply predetermined tensile loading on the nanofibers under cell culture conditions. The results indicated that piezo-potential ranging from 11 to 103 μV could be produced by cell adhesion forces varied between 1 and 15 nN, while mechanical loading ranging from 1 % to 15 % strain resulted in piezoelectrical signals in the magnitude of several volts. These piezoelectric signals could influence cell adhesion through enhancing cell aspect ratio and cell area. During the process of cell contraction and re-spreading caused by the mechanical loading, the piezoelectric signals were capable of accelerating the recovery of spreading and adhesion. Furthermore, individual piezoelectric and mechanical signals could modulate intracellular calcium signals, and significantly promote osteogenic differentiation of MSCs. Specifically, the mechanical stimulation could activate PIEZO signaling pathway, resulting in a greater upregulation of early osteogenic differentiation markers of Collagen type I and Bone morphogenetic protein-2 compared to the piezoelectric signal. However, the combination of the two stimuli could obviously and effectively enhance osteogenic differentiation of MSCs in a synergistic manner. These findings offer fresh understandings regarding the electromechanical influences in the process of bone tissue regeneration, which afford additional possibilities for optimizing piezoelectric biomaterials for biomedical applications in a more reasonable manner.

Effect of Electrical Stimulation on PC12 Cells Cultured in Different Hydrogels: Basis for the Development of Biomaterials in Peripheral Nerve Tissue Engineering.

Extensive damage to peripheral nerves is a health problem with few therapeutic alternatives. In this context, the development of tissue engineering seeks to obtain materials that can help recreate environments conducive to cellular development and functional repair of peripheral nerves. Different hydrogels have been studied and presented as alternatives for future treatments to emulate the morphological characteristics of nerves. Along with this, other research proposes the need to incorporate electrical stimuli into treatments as agents that promote cell growth and differentiation; however, no precedent correlates the simultaneous effects of the types of hydrogel and electrical stimuli. This research evaluates the neural differentiation of PC12 cells, relating the effect of collagen, alginate, GelMA, and PEGDA hydrogels with electrical stimulation modulated in four different ways. Our results show significant correlations for different cultivation conditions. Electrical stimuli significantly increase neural differentiation for specific experimental conditions dependent on electrical frequency, not voltage. These backgrounds allow new material treatment schemes to be formulated through electrical stimulation in peripheral nerve tissue engineering.

Fish waste-derived biomaterial as a support of zero waste and Sustainable Development Goals (SDGs)

Fish is a source of animal protein consumed by people worldwide. Its use for health and abundant fish production makes some countries or regions have high consumption compared to other animal protein sources. This study aims to review the potential of fish as a biomaterial to support zero waste and achieve the SDGs. This study reviews journals originating from Science Direct in narrative reviews of skin, scale, and bone waste from fish as biomaterials and the connection between zero waste efforts and SDGs. This study found that fish waste can be recycled into collagen, gelatin, hydroxyapatite, and calcium phosphate as biomaterials for bone tissue engineering, drug delivery, health, cosmetic, food, and pharmaceutical industries. It supports zero waste efforts and the achievement of SDGs in good health and well-being, responsible production and consumption, and decent work and economic growth.

Applications of Light-Based 3D Bioprinting and Photoactive Biomaterials for Tissue Engineering

The emergence of additive manufacturing, commonly referred to as 3D printing, has led to a revolution in the field of biofabrication. Numerous types of 3D bioprinting, including extrusion bioprinting, inkjet bioprinting, and lithography-based bioprinting, have been developed and have played pivotal roles in driving a multitude of pioneering breakthroughs in the fields of tissue engineering and regenerative medicine. Among all the 3D bioprinting methods, light-based bioprinting utilizes light to crosslink or solidify photoreactive biomaterials, offering unprecedented spatiotemporal control over biomaterials and enabling the creation of 3D structures with extremely high resolution and precision. However, the lack of suitable photoactive biomaterials has hindered the application of light-based bioprinting in tissue engineering. The development of photoactive biomaterials has only recently been expanded. Therefore, this review summarizes the latest advancements in light-based 3D bioprinting technologies, including the development of light-based bioprinting techniques, photo-initiators (PIs), and photoactive biomaterials and their corresponding applications. Moreover, the challenges facing bioprinting are discussed, and future development directions are proposed.

Gelatin methacryloyl granular scaffolds for localized mRNA delivery

AbstractMessenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra‐articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease‐mediated degradation and safe site‐specific intracellular delivery. Herein, novel mRNA‐releasing matrices based on RGD‐moiety‐rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel‐based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA‐releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA‐releasing biomaterials for tissue engineering.