Integrated and Bifunctional Bilayer 3D Printing Scaffold for Osteochondral Defect Repair

Bioinspired scaffolds with two distinct regions resembling stratified anatomical architecture provide potential strategies for osteochondral defect repair and are studied in preclinical animals. However, delamination of the two layers often causes tissue disjunction between the regenerated cartilage and subchondral bone, leading to few commercially available clinical applications. This study develops an integrated poly(ε-caprolactone) (PCL)-based scaffold for repairing osteochondral defects. An extracellular matrix (ECM)-incorporated 3D printing composite scaffold (ECM/PCL) coated with ECM hydrogel (E-co-E/PCL) is fabricated as the upper layer, and magnesium oxide nanoparticles coated with polydopamine (MgO@PDA)-incorporated composite scaffold (MD/PCL) is fabricated using 3D printing as the bottom layer. The physicochemical and mechanical properties of the bilayer scaffold meet the requirements in designing and fabricating the osteochondral scaffold, especially a strong interface possessed between the two layers. By in vitro study, the integrated scaffold stimulates proliferation, chondrogenic differentiation, and osteogenic differentiation of human bone mesenchymal stem cells. Moreover, the integrated bilayer scaffold exhibits well repair ability to facilitate simultaneous regeneration of cartilage and subchondral bone after implanting into the osteochondral defect in rats. In addition, cartilage “tidemarks” completely regenerated after 12 weeks of implantation of the bilayer scaffold, which indicates no tissue disjunctions formed between the regenerated cartilage and subchondral bone.     

A Bi‐Lineage Conducive Scaffold for Osteochondral Defect Regeneration

Because cartilage and bone tissues have different lineage‐specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium‐containing mesoporous bioglass (Li‐MBG) scaffold is developed. The efficacy and mechanism of Li‐MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro‐CT results show that Li‐MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage‐like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li‐MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi‐lineage conducive scaffolds that enhance regeneration of osteochondral defects.     

Polymer Fiber Scaffolds for Bone and Cartilage Tissue Engineering

Successful regeneration of weight‐bearing bone defects and critical‐sized cartilage defects remains a major challenge in clinical orthopedics. In the past decades, biodegradable polymer materials with biomimetic chemical and physical properties have been rapidly developed as ideal candidates for bone and cartilage tissue engineering scaffolds. Due to their unique advantages over other materials of high specific‐surface areas, suitable mechanical strength, and tailorable characteristics, scaffolds made of polymer fibers have been increasingly used for the repair of bone and cartilage defects. This Review summarizes the preparation and compositions of polymer fibers, as well as their characteristics. More importantly, the applications of polymer fiber scaffolds with well‐designed structures or unique properties in bone, cartilage, and osteochondral tissue engineering have been comprehensively highlighted. On the whole, such a comprehensive summary affords constructive suggestions for the development of polymer fiber scaffolds in bone and cartilage tissue engineering.     

3D Printing of Bilineage Constructive Biomaterials for Bone and Cartilage Regeneration

Owing to the different biological properties of articular cartilage and subchondral bone, it remains significant challenge to construct a bi‐lineage constructive scaffold. In this study, manganese (Mn)‐doped β‐TCP (Mn‐TCP) scaffolds with varied Mn contents are prepared by a 3D‐printing technology. The effects of Mn on the physicochemical properties, bioactivity, and corresponding mechanism for stimulating osteochondral regeneration are systematically investigated. The incorporation of Mn into β‐TCP lowers the lattices parameters and crystallization temperatures, but improves the scaffold density and compressive strength. The ionic products from Mn‐TCP significantly improve the proliferation of both rabbit chondrocytes and mesenchymal stem cells (rBMSCs), as well as promote the differentiation of chondrocytes and rBMSCs. The in vivo study shows that Mn‐TCP scaffolds distinctly improve the regeneration of subchondral bone and cartilage tissues as compared to TCP scaffolds, upon transplantation in rabbit osteochondral defects for 8 and 12 weeks. The mechanism is closely related to the Mn²⁺ ions significantly stimulated the proliferation and differentiation of chondrocytes through activating HIF pathway and protected chondrocytes from the inflammatory osteoarthritis environment by activating autophagy. These findings suggest that 3D‐printing of Mn‐containing scaffolds with improved physicochemical properties and bilineage bioactivities represents an intelligent strategy for regenerating osteochondral defects.     

Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ? sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.     

3D Printing Hydrogel Scaffolds with Nanohydroxyapatite Gradient to Effectively Repair Osteochondral Defects in Rats

Osteochondral (OC) defects pose an enormous challenge with no entirely satisfactory repair strategy to date. Herein, a 3D printed gradient hydrogel scaffold with a similar structure to that of OC tissue is designed, involving a pure hydrogel-based top cartilage layer, an intermediate layer for calcified cartilage with 40% (w w⁻¹) nanohydroxyapatite (nHA) and 60% (w w⁻¹) hydrogel, and a 70/30% (w w⁻¹) nHA/hydrogel-based bottom subchondral bone layer. This study is conducted to evaluate the efficacy of the scaffold with nHA gradients in terms of its ability to promote OC defect repair. The fabricated composites are evaluated for physicochemical, mechanical, and biological properties, and then implanted into the OC defects in 56 rats. Overall, bone marrow stromal cells (BMSCs)-loaded gradient scaffolds exhibit superior repair results as compared to other scaffolds based on gross examination, micro-computed tomography (micro-CT), as well as histologic and immunohistochemical analyses, confirming the ability of this novel OC graft to facilitate simultaneous regeneration of cartilage-subchondral bone.     

Biomimetic Composite Scaffolds to Manipulate Stem Cells for Aiding Rheumatoid Arthritis Management

Stem cell transplantation is a promising alternative therapy for rheumatoid arthritis (RA) patients, with the potential to suppress autoimmune in?ammation and prevent joint damage. However, widespread application of RA therapy based on stem cell transplantation is limited due to poor migration, local retention, and uncontrolled differentiation of stem cells. Here, inspired by the dynamic construction of bone matrix, a structurally and functionally optimized scaffold for loading bone marrow stem cells (BMSCs) is designed to aid RA management. The composite scaffolds consist of stiff 3D printing porous metal scaffolds (3DPMS) and soft multifunctional polysaccharide hydrogels, wherein 3DPMS meet the requirements for large‐scale bone defects caused by RA. Attractively, the fabricated hydrogels on the composite scaffold are self‐healable, injectable, biocompatible, and biodegradable, which endow the resultant scaffold many aspects mimicking the extracellular matrix (ECM). After encapsulation of BMSCs, hydrogels are administered into the inner pores of 3DPMS, abbreviated as BMSCs@3DPMS/hydrogels. In this study, BMSCs@3DPMS/hydrogels have a good effect on improving RA, such as remodeling of knee joint articular cartilage, inhibition of in?ammatory cytokines, and promotion of subchondral bone regeneration. Besides RA, the innovative scaffolds may also serve as an ideal biomaterial for other bone regenerative therapies in various orthopedic diseases.     

Magnesium Gradient-Based Hierarchical Scaffold for Dual-Lineage Regeneration of Osteochondral Defect

Osteochondral regeneration remains a great challenge due to the limited self-healing ability and the complexity of its hierarchical structure and composition. Mg²⁺ and hypoxia are two effective modulators in boosting chondrogenesis. To this end, a double-layered scaffold (D) consisting of a hydrogel layer on a porous cryogel is fabricated to mimic the hierarchical structure of osteochondral tissue. An Mg²⁺ gradient is incorporated into the double-layered scaffold with hypoxia-mimicking deferoxamine (DFO) embedded in the hydrogel (D-Mg-DFO), which remarkably augments the dual-lineage regeneration of both cartilage and subchondral bone. The higher Mg²⁺ supplementation from the upper hydrogel, associated with its hypoxia-mimicking situation and small pore size, exhibits promotive effects on chondrogenic differentiation. The lower Mg²⁺ supplementation from the bottom cryogel, associated with its interconnected macroporous structure, achieves multiple contributions in stem cell migration from bone marrow cavity, matrix mineralization, and osteogenesis. Furthermore, rabbits’ trochlea osteochondral defects are established to evaluate the regenerative outcome. Compared to control scaffolds containing only Mg²⁺ or DFO, the D-Mg-DFO scaffold presents the best regenerative effect under the synergistic contribution of multiple factors. Overall, this work provides a new design of scaffold toward an effective repair of cartilage defect.     

Micro/Nanometer‐Structured Scaffolds for Regeneration of Both Cartilage and Subchondral Bone

Treatment of osteochondral defects remains a great challenge in clinical practice because cartilage and subchondral bone possess significantly different physiological properties. In this study, the controlled surface micro/nanometer structure of bioactive scaffolds in a combination of biomaterial chemistry is harnessed to address this issue. Model bioactive biomaterials, bredigite (BRT) scaffolds, with controlled surface micro/nanostructure are successfully fabricated by combining 3D printing with a hydrothermal process. It is found that the growth of micro/nano–calcium phosphate crystals on the surface of BRT scaffolds notably enhances their compressive strength by healing the microcracks on the strut surface. The micro/nanostructured surface distinctly facilitates the spread and differentiation of chondrocytes by activating integrin αvb1 and α5b1 heterodimers, regulates cell morphology, and promotes osteogenic differentiation of rabbit bone marrow stromal cells (rBMSCs) through the synergetic effect of integrin α5b1 and RhoA, in which the microrod surface demonstrates the highest stimulatory effect on the differentiation of chondrocytes and rBMSCs. The in vivo study shows that the micro/nanostructured surface of the 3D printed scaffolds obviously promotes the regeneration of both cartilage and subchondral bone tissues. This study suggests that the construction of controlled micro/nanostructured surface in porous 3D scaffolds offers a smart strategy to induce bilineage bioactivities for osteochondral regeneration.     

3D Superelastic Scaffolds Constructed from Flexible Inorganic Nanofibers with Self‐Fitting Capability and Tailorable Gradient for Bone Regeneration

Repair of bone defects with irregular shapes or at soft tissue insertion sites faces a huge challenge. Scaffolds capable of adapting to bone cavities, generating stiffness gradients, and inducing osteogenesis are necessary. Herein, a superelastic 3D ceramic fibrous scaffold is developed by assembly of intrinsically rigid, structurally flexible electrospun SiO₂ nanofibers with chitosan as bonding sites (SiO₂ NF‐CS) via a lyophilization technique. SiO₂ NF‐CS scaffolds exhibit excellent elasticity (full recovery from 80% compression), fast recovery rate (>500 mm min^?1), and good fatigue resistance (>10 000 cycles of compression) in an aqueous medium. SiO₂ NF‐CS scaffolds induce human mesenchymal stem cell (hMSC) elongation and differentiation into osteoblasts. In vivo self‐fitting capability is demonstrated by implanting compressed SiO₂ NF‐CS scaffolds into different shaped mandibular defects in rabbits, with a spontaneous recovery and full filling of defects. Rat calvarial defect repair validates enhanced bone formation and vascularization by cell (hMSC) histomorphology analysis. Further, subchondral bone scaffolds with gradations in SiO₂ nanofibers are developed, leading to a stiffness gradient and spatially chondrogenic and osteogenic differentiation of hMSCs. This work presents a type of 3D ceramic fibrous scaffold, which can closely match bone defects with irregular shapes or at different implant sites, and is promising for clinical translation.     

Biomimetic Elastomeric Bioactive Siloxane‐Based Hybrid Nanofibrous Scaffolds with miRNA Activation: A Joint Physico‐Chemical‐Biological Strategy for Promoting Bone Regeneration

Rapid and efficient disease‐induced or critical‐size bone regeneration remains a challenge in tissue engineering due to the lack of highly bioactive biomaterial scaffolds. Physical structures such as nanostructures, chemical components such as silicon elements, and biological factors such as genes have shown positive effects on bone regeneration. Herein, a bioactive photoluminescent elastomeric silicate‐based nanofibrous scaffold with sustained miRNA release is reported for promoting bone regeneration based on a joint physico‐chemical‐biological strategy. Bioactive nanofibrous scaffolds are fabricated by cospinning poly (ε‐caprolactone) (PCL), elastomeric poly (citrates‐siloxane) (PCS), and bioactive osteogenic miRNA nanocomplexes (denoted PPM nanofibrous scaffolds). The PPM scaffolds possess uniform nanostructures, significantly enhanced tensile stress (≈15 MPa) and modulus (≈32 MPa), improved hydrophilicity (30–60°), controlled biodegradation, and strong blue fluorescence. Bioactive miRNA complexes are efficiently loaded into the nanofibrous matrix and exhibit long‐term release for up to 70 h. The PPM scaffolds significantly promote the adhesion, proliferation, and osteoblast differentiation of bone marrow stem cells in vitro and enhanced rat cranial defect restoration (12 weeks) in vivo. This work reports an attractive joint physico‐chemical‐biological strategy for the design of novel cell/protein‐free bioactive scaffolds for synergistic tissue regeneration.     

Biomimetic Scaffolds for Tissue Engineering

Biomimetic scaffolds mimic important features of the extracellular matrix (ECM) architecture and can be finely controlled at the nano‐ or microscale for tissue engineering. Rational design of biomimetic scaffolds is based on consideration of the ECM as a natural scaffold; the ECM provides cells with a variety of physical, chemical, and biological cues that affect cell growth and function. There are a number of approaches available to create 3D biomimetic scaffolds with control over their physical and mechanical properties, cell adhesion, and the temporal and spatial release of growth factors. Here, an overview of some biological features of the natural ECM is presented and a variety of original engineering methods that are currently used to produce synthetic polymer‐based scaffolds in pre‐fabricated form before implantation, to modify their surfaces with biochemical ligands, to incorporate growth factors, and to control their nano‐ and microscale geometry to create biomimetic scaffolds are discussed. Finally, in contrast to pre‐fabricated scaffolds composed of synthetic polymers, injectable biomimetic scaffolds based on either genetically engineered‐ or chemically synthesized‐peptides of which sequences are derived from the natural ECM are discussed. The presence of defined peptide sequences can trigger in situ hydrogelation via molecular self‐assembly and chemical crosslinking. A basic understanding of the entire spectrum of biomimetic scaffolds provides insight into how they can potentially be used in diverse tissue engineering, regenerative medicine, and drug delivery applications.     

A Bifunctional Biomaterial with Photothermal Effect for Tumor Therapy and Bone Regeneration

Malignant bone tumor is one of the major bone diseases. The treatment of such a bone disease typically requires the removal of bone tumor and regeneration of tumor‐initiated bone defects simultaneously. To address this issue, it is required that implanted biomaterials should combine the bifunctions of both therapy and regeneration. In this work, a bifunctional graphene oxide (GO)‐modified β‐tricalcium phosphate (GO‐TCP) composite scaffold combining a high photothermal effect with significantly improved bone‐forming ability is prepared by 3D‐printing and surface‐modification strategies. The prepared GO‐TCP scaffolds exhibit excellent photothermal effects under the irradiation of 808 nm near infrared laser (NIR) even at an ultralow power density of 0.36 W cm^?2, while no photothermal effects are observed for pure β‐TCP scaffolds. The photothermal temperature of GO‐TCP scaffolds can be effectively modulated in the range of 40–90 °C by controlling the used GO concentrations, surface‐modification times, and power densities of NIR. The distinct photothermal effect of GO‐TCP scaffolds induces more than 90% of cell death for osteosarcoma cells (MG‐63) in vitro, and further effectively inhibits tumor growth in mice. Meanwhile, the prepared GO‐TCP scaffolds possess the improved capability to stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) by upregulating bone‐related gene expression, and significantly promote new bone formation in the bone defects of rabbits as compared to pure β‐TCP scaffolds. These results successfully demonstrate that the prepared GO‐TCP scaffolds have bifunctional properties of photothermal therapy and bone regeneration, which is believed to pave the way to design and fabricate novel implanting biomaterials in combination of therapy and regeneration functions.     

Smart Biomaterials for Articular Cartilage Repair and Regeneration

Articular cartilage defects bring about disability and worldwide socioeconomic loss, therefore, articular cartilage repair and regeneration is recognized as a global issue. However, due to its avascular and nearly acellular characteristic, cartilage tissue regeneration ability is limited to some extent. Despite the availability of various treatment methods, including palliative drugs and surgical regenerative therapy, articular cartilage repair and regeneration still face major challenges due to the lack of appropriate methods and materials. Smart biomaterials can regulate cell behavior and provide excellent tissue repair and regeneration microenvironment, thus inducing articular cartilage repair and regeneration. This process is adjusted by controlling drug/bioactive factors release via responding to exogenous/endogenous stimuli, tailoring materials’ structure and function similar to native cartilage or providing physiochemical and physical signaling factors. Herein, smart biomaterials, recently applied in articular cartilage repair and regeneration, are elaborated from two aspects: smart drug release system and smart scaffolds. Furthermore, articular cartilage and its defects and advanced manufacturing techniques of smart biomaterials are discussed in brief. Finally, perspectives for smart biomaterials used in articular cartilage repair and regeneration are presented and the clinical translation of smart biomaterials is emphasized.     

Cocrystal Strategy toward Multifunctional 3D‐Printing Scaffolds Enables NIR‐Activated Photonic Osteosarcoma Hyperthermia and Enhanced Bone Defect Regeneration

Malignant bone tumors are one of the major serious diseases in clinic. Inferior reconstruction of new bone and rapid propagation of residual tumor cells are the main challenges to surgical intervention. Herein, a bifunctional DTC@BG scaffold for near‐infrared (NIR)‐activated photonic thermal ablation of osteosarcoma and accelerated bone defect regeneration is engineered by in situ growth of NIR‐absorbing cocrystal (DTC) on the surface of a 3D‐printing bioactive glass (BG) scaffold. The prominent photothermal conversion performance and outstanding bone regeneration capability of DTC@BG scaffolds originate from the precise tailoring of the bandgap between the electron donors and acceptors of DTC and promote new bone growth performance of BG scaffolds. DTC@BG scaffolds not only significantly promote tumor cell ablation in vitro, but also effectively facilitate bone tumor suppression in vivo. In particular, DTC@BG scaffolds exhibit excellent capability in stimulating osteogenic differentiation and angiogenesis, and finally promote newborn bone formation in the bone defects. This research represents the first paradigm for ablating osteosarcoma and facilitating new bone formation through precise modulation of electron donors and acceptors in the cocrystal, which offers a new avenue to construct high‐efficiency therapeutic platforms based on cocrystal strategy for ablation of malignant bone tumor.     

Biomimetic Structures: Biological Implications of Dipeptide‐Substituted Polyphosphazene–Polyester Blend Nanofiber Matrices for Load‐Bearing Bone Regeneration

Successful bone regeneration benefits from three‐dimensional (3D) bioresorbable scaffolds that mimic the hierarchical architecture and mechanical characteristics of native tissue extracellular matrix (ECM). A scaffold platform that integrates unique material chemistry with nanotopography while mimicking the 3D hierarchical bone architecture and bone mechanics is reported. A biocompatible dipeptide polyphosphazene‐polyester blend is electrospun to produce fibers in the diameter range of 50–500 nm to emulate dimensions of collagen fibrils present in the natural bone ECM. Various electrospinning and process parameters are optimized to produce blend nanofibers with good uniformity, appropriate mechanical strength, and suitable porosity. Biomimetic 3D scaffolds are created by orienting blend nanofiber matrices in a concentric manner with an open central cavity to replicate bone marrow cavity, as well as the lamellar structure of bone. This biomimicry results in scaffold stress–strain curve similar to that of native bone with a compressive modulus in the mid‐range of values for human trabecular bone. Blend nanofiber matrices support adhesion and proliferation of osteoblasts and show an elevated phenotype expression compared to polyester nanofibers. Furthermore, the 3D structure encourages osteoblast infiltration and ECM secretion, bridging the gaps of scaffold concentric walls during in vitro culture. The results also highlight the importance of in situ ECM secretion by cells in maintaining scaffold mechanical properties following scaffold degradation with time. This study for the first time demonstrates the feasibility of developing a mechanically competent nanofiber matrix via a biomimetic strategy and the advantages of polyphosphazene blends in promoting osteoblast phenotype progression for bone regeneration.     

Advanced Collagen‐Based Biomaterials for Regenerative Biomedicine

In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.     

Solid Free‐Form Fabrication of Tissue‐Engineering Scaffolds with a Poly(lactic‐co‐glycolic acid) Grafted Hyaluronic Acid Conjugate Encapsulating an Intact Bone Morphogenetic Protein–2/Poly(ethylene glycol) Complex

Despite wide applications of bone morphogenetic protein–2 (BMP‐2), there are few methods to incorporate BPM‐2 within polymeric scaffolds while maintaining biological activity. Solid free‐form fabrication (SFF) of tissue‐engineering scaffold is successfully carried out with poly(lactic‐co‐glycolic acid) grafted hyaluronic acid (HA‐PLGA) encapsulating intact BMP‐2/poly(ethylene glycol) (PEG) complex. HA‐PLGA conjugate is synthesized in dimethyl sulfoxide (DMSO) by the conjugation reaction of adipic acid dihydrazide modified HA (HA‐ADH) and PLGA activated with N,N′‐dicyclohexylcarbodiimide (DCC) and N‐hydroxysuccinimide (NHS). BMP‐2 is complexed with PEG, which is encapsulated within the PLGA domain of the HA‐PLGA conjugate by SFF to prepare tissue‐engineering scaffolds. In vitro release tests confirm the sustained release of intact BMP‐2 from the scaffolds for up to a month. After confirmation of the enhanced osteoblast cell growth, and high gene‐expression levels of alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX) in the cells, the HA‐PLGA/PEG/BMP‐2 scaffolds are implanted into calvarial bone defects of Sprague Dawley (SD) rats. Microcomputed tomography (μCT) and histological analyses with Masson's trichrome, and hematoxylin and eosin (H&E) staining reveal effective bone regeneration on the scaffolds of HA‐PLGA/PEG/BMP‐2 blends.     

Injectable,Self-Contained,Subaqueously Cross-Linking Laminous Adhesives for Biophysical-Chemical Modulation of Osteochondral Microenvironment

Current osteochondral (OC) defect repair approaches using premade scaffolds face clinical limitations due to invasiveness, weak integrity, and/or insufficient interfacial bonding. An injectable hydrophobic laminous adhesive is developed that rapidly photocross-link subaqueously and forms robust bi-layered structure that orchestrates biophysical-chemical cues for stimulating OC repair. Liquid hydrophobic photo-cross-linkable poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (P_mL_nDMA) are adopted as cartilage phase and P_mL_nDMA encapsulating methacrylated hydroxyapatite nanoparticles (P_mL_nDMA/MH) as the mineralized subchondral bone phase. Both phases exhibit strong interfacial bonding due to the presence of “CC”. Mechanotransduction and growth factor-mediated signaling pathways are enchanced by matching the mechanical properties of two phases to native cartilage and bone via systematical modulation of the adhesives’ composition and encapsulated growth factors’ release profile. This enhances mesenchymal stem cells’ commitment to corresponding chondrocytes and osteoblasts to augment OC repair in vitro and in vivo, and ultimately benefits patients suffering from OC fracture, osteoarthritis, and osteoporosis.     

Electrospun Extracellular Matrix: Paving the Way to Tailor‐Made Natural Scaffolds for Cardiac Tissue Regeneration

Biomimetic scaffolds generally aim at structurally and compositionally imitating native tissue, thus providing a supportive microenvironment to the transplanted or recruited cells in the tissue. Native decellularized porcine extracellular matrix (ECM) is becoming the ultimate bioactive material for the regeneration of different organs. Particularly for cardiac regeneration, ECM is studied as a patch and injectable scaffolds, which improve cardiac function, yet lack reproducibility and are difficult to control or fine‐tune for the desired properties, like most natural materials. Seeking to harness the natural advantages of ECM in a reproducible, scalable, and controllable scaffold, for the first time, a matrix that is produced from whole decellularized porcine cardiac ECM using electrospinning technology, is developed. This unique electrospun cardiac ECM mat preserves the composition of ECM, self‐assembles into the same microstructure of cardiac ECM ,and ,above all, preserves key cardiac mechanical properties. It supports cell growth and function, and demonstrates biocompatibility in vitro and in vivo. Importantly, this work reveals the great potential of electrospun ECM‐based platforms for a wide span of biomedical applications, thus offering the possibility to produce complex natural materials as tailor‐made, well‐defined structures.