Escalating cases of organ shortage and donor scarcity worldwide are alarming reminders of the need for alternatives to allograft tissues. Within the last three decades, research efforts in the field ...of regenerative medicine and tissue engineering continue to address the unmet need for artificial tissues and organs for transplant. Work in the field has evolved to create what we consider a new field, Regenerative Engineering, defined as the Convergence of advanced materials science, stem cell science, physics, developmental biology and clinical translation towards the regeneration of complex tissues and organ systems. Included in the regenerative engineering paradigm is advanced manufacturing. Three-dimensional (3D) bioprinting is a promising and innovative biofabrication strategy to precisely position biologics, including living cells and extracellular matrix (ECM) components, in the prescribed 3D hierarchal organization to create artificial multi-cellular tissues/organs. In this review, we outline recent progress in several bioprinting technologies used to engineer scaffolds with requisite mechanical, structural, and biological complexity. We examine the process parameters affecting bioprinting and bioink-biomaterials and review notable studies on bioprinted skin, cardiac, bone, cartilage, liver, lung, neural, and pancreatic tissue. We also focus on other 3D bioprinting application areas including cancer research, drug testing, high-throughput screening (HTS), and organ-on-a-chip models. We also highlight the current challenges associated with the clinical translation of 3D bioprinting and conclude with the future perspective of bioprinting technology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As a member of the polyhydroxyalkanoate (PHAs) family, Poly(3-hydroxybutyrate) (PHB) has attracted much attention for a variety of medical applications because of its desirable properties such as ...high biocompatibility, nontoxic degradation products and high mechanical strength in comparison to other polymers in different fields including tissue engineering. There are different approaches such as making PHB alloy scaffolds, using PHB as a coating for ceramic-based scaffolds and producing composite scaffolds by using a mixture of PHB with ceramic particles utilized to improve hydrophobicity, degradation rate and brittleness. In this review, different applications of PHB, its alloys and composites in tissue engineering are explained based on the common methods of fabrication such as polymeric sponge replication, electrospinning and salt leaching.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for ...efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb2C MXene wrapped with S‐nitrosothiol (RSNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.
The multifunctional biomaterial system integrates photonic hyperthermia of MXene in near infrared (NIR)‐II biowindow with precisely controlled nitric oxide (NO) release for multitarget ablation of bone tumors and localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from bioactive glass (BG) scaffold promote bone‐regeneration bioactivity, which is further augmented by sufficient blood supply triggered by on‐demand NO release.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The traditional production methods of porous magnesium scaffolds are difficult to accurately control the pore morphologies and simultaneously obtain appropriate mechanical properties. In this work, ...two open-porous magnesium scaffolds with different pore size but in the nearly same porosity are successfully fabricated with high-purity Mg ingots through the titanium wire space holder (TWSH) method. The porosity and pore size can be easily, precisely and individually controlled, as well as the mechanical properties also can be regulated to be within the range of human cancellous bone by changing the orientation of pores without sacrifice the requisite porous structures. In vitro cell tests indicate that the scaffolds have good cytocompatibility and osteoblastic differentiation properties. In vivo findings demonstrate that both scaffolds exhibit acceptable inflammatory responses and can be almost fully degraded and replaced by newly formed bone. More importantly, under the same porosity, the scaffolds with larger pore size can promote early vascularization and up-regulate collagen type 1 and OPN expression, leading to higher bone mass and more mature bone formation. In conclusion, a new method is introduced to develop an open-porous magnesium scaffold with controllable microstructures and mechanical properties, which has great potential clinical application for bone reconstruction in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bacterial cellulose produced by few but specific microbial genera is an extremely pure natural exopolysaccharide. Besides providing adhesive properties and a competitive advantage to the cellulose ...over-producer, bacterial cellulose confers UV protection, ensures maintenance of an aerobic environment, retains moisture, protects against heavy metal stress, etc. This unique nanostructured matrix is being widely explored for various medical and nonmedical applications. It can be produced in various shapes and forms because of which it finds varied uses in biomedicine. The attributes of bacterial cellulose such as biocompatibility, haemocompatibility, mechanical strength, microporosity and biodegradability with its unique surface chemistry make it ideally suited for a plethora of biomedical applications. This review highlights these qualities of bacterial cellulose in detail with emphasis on reports that prove its utility in biomedicine. It also gives an in-depth account of various biomedical applications ranging from implants and scaffolds for tissue engineering, carriers for drug delivery, wound-dressing materials, etc. that are reported until date. Besides, perspectives on limitations of commercialisation of bacterial cellulose have been presented. This review is also an update on the variety of low-cost substrates used for production of bacterial cellulose and its nonmedical applications and includes patents and commercial products based on bacterial cellulose.
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CEKLJ, DOBA, EMUNI, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing ...can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and ...long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.
This review highlights the recent developments of surface modification and endothelialization of biomaterials in vascular tissue engineering applications.
A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated ...tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.
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IJS, NUK, SBMB, UL, UM, UPUK
3D printing technology has attracted much attention due to its high potential in scientific and industrial applications. As an outstanding 3D printing technology, two-photon polymerization (TPP) ...microfabrication has been applied in the fields of micro/nanophotonics, micro-electromechanical systems, microfluidics, biomedical implants and microdevices. In particular, TPP microfabrication is very useful in tissue engineering and drug delivery due to its powerful fabrication capability for precise microstructures with high spatial resolution on both the microscopic and the nanometric scale. The design and fabrication of 3D hydrogels widely used in tissue engineering and drug delivery has been an important research area of TPP microfabrication. The resolution is a key parameter for 3D hydrogels to simulate the native 3D environment in which the cells reside and the drug is controlled to release with optimal temporal and spatial distribution
in vitro
and
in vivo
. The resolution of 3D hydrogels largely depends on the efficiency of TPP initiators. In this paper, we will review the widely used photoresists, the development of TPP photoinitiators, the strategies for improving the resolution and the microfabrication of 3D hydrogels.
Arbitrary and ultraprecise 3D hydrogels with high resolution on micro/nano scale can be produced by two-photon polymerization microfabrication as an advanced 3D printing technology.
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