Biodegradable polylactic acid-based microspheres have been widely used in biomedical applications such as drug delivery and tissue engineering, however, most of the microspheres typically possess simple surface structures, lacking bioactivity and the ability to promote cell adhesion. Our group previously synthesized poly (L-lactic acid) magnesium-doped microspheres (PMg) with immunomodulatory and osteogenic potential. However, several drawbacks of PMgs, such as high hydrophobicity, a narrow pore distribution and large average particle size, and limited sustainable Mg2+release, can affect cell adhesion and growth and thus restricting their biomedical applications. To address these limitations, in the current study, a poly (lactic acid)-poly (ethylene glycol)-poly (lactic acid) (PLEL) triblock copolymer was synthesized, and magnesium-incorporated PLEL porous microspheres (PEMg) were prepared through emulsion solvent evaporation combined with anin-situdoping method. Benefiting from hydrophilic PEG segments, PEMg displayed significantly improved surface wettability and structural stability. The optimized PEMg possessed nearly half of the average size of PMg. and an interconnected hierarchical larger pore structure (1-30 μm, average: 10 ± 1.4 μm), which effectively promoted cell adhesion and deep infiltration. Moreover, PEMg showed a sustained Mg2+release which is nearly 1.87-fold higher than PMg, capable of neutralizing acidic by-products and stabilizing the local microenvironment. The biocompatible PEMg could upregulate anti-inflammatory biomarkers (Arg-1, CD206) and inhibit pro-inflammatory factors (iNOS, TNF-α), achieving over 1.5 times anti-inflammatory capacity of PMg. In summary, the creatively developed PEMg microspheres integrate optimized structural features and enhanced biological performances. Compared with PMg, PEMg showed much better potential to satisfy the complex demands of tendon soft tissue repair and presents promising prospects for inflammatory microenvironment regulation and soft tissue regeneration.
Precise regulation of vascular endothelial growth factor (VEGF) delivery is essential for angiogenesis-oriented tissue engineering, because excessive or poorly controlled VEGF exposure may lead to abnormal and immature vascular structures. In this study, aligned core-shell fibrous threads loaded with deoxycholic acid-modified branched polyethylenimine/plasmid encoding VEGF (bPEI1.8-DA/plasmids encoding vascular endothelial growth factor (pVEGF)) polyplexes were developed as a scaffold-mediated platform for sustained VEGF gene delivery. The polymer/plasmid DNA weight ratio was first optimized in human umbilical vein endothelial cells (HUVECs), and a ratio of 2 was selected based on reporter-gene expression and cytocompatibility. The pVEGF polyplexes were then incorporated into the aqueous core of gelatin/poly(ϵ-caprolactone) (70:30) fibers using modified coaxial electrospinning equipped with a rotating disk collector. Electron and fluorescence microscopy confirmed the formation of bead-free aligned fibers with a core-shell architecture and successful polyplex incorporation. The aligned fibers were twisted into cohesive fibrous threads with an average diameter of approximately 148 μm. Genipin crosslinking preserved the fibrous morphology, improved scaffold stability, and increased Young's modulus from 37.13 to 49.81 cN/Tex while reducing extensibility.In vitrorelease studies showed that the core-shell structure, crosslinking, and compact thread architecture reduced the initial burst release and prolonged polyplex delivery over 33 d. The initial polyplex release from crosslinked threads was 16.59%, approximately 35% lower than that from crosslinked webs, and the released polyplex amount remained below the 100 ng threshold level for up to 16 d. Released polyplexes retained reporter-gene expression capability, and enzyme-linked immunosorbent assay confirmed prolonged VEGF secretion by HUVECs. The scaffolds also supported cell adhesion and metabolic activity. These findings indicate that aligned core-shell fibrous threads can provide sustained plasmid polyplex availability, prolong downstream VEGF secretion, and serve as a promising platform for localized angiogenic gene delivery, particularly in applications requiring directional fibrous architecture and localized vector delivery.
BiofabricationAlireza Nemati, Anu David, Yuxuan Zhang, Houman Savoji, Christophe Faure
Esophageal reconstruction is one of the most challenging procedures in gastrointestinal surgery. While conventional therapeutic approaches, such as gastric pull-up and intestinal interposition, can restore continuity, they often fail to replicate native physiology. This limitation frequently leads to long-term complications, including dysphagia, stricture, and reflux, which can significantly affect the patients' quality of life. Tissue engineering approaches offer promising alternatives aimed at developing esophageal constructs that restore both structure and function, addressing the shortcomings of current treatment methods. This review highlights recent progress in esophageal tissue engineering (ETE), focusing on the requirements for ideal ETE scaffolds and examining available biomaterials, including natural, synthetic, and hybrid. We discuss advances in fabrication techniques and various cell-based approaches, such as primary cells, stem cells, and organoids. Furthermore, we also review the steps necessary to transition ETE constructs from the laboratory to clinical settings (ongoing human trials), including preclinical studies conducted on rodent, rabbit, canine, and porcine models with the expected functional outcomes and regeneration capabilities. Early translational efforts in ETE are addressed, along with the regulatory and ethical considerations regarding good manufacturing practice (GMP) compliance, traceability, and long-term surveillance. While significant advancements in ETE have been made in preclinical models, the review also discusses the challenges of moving to clinical studies. Potential strategies to address these challenges, such as 4-dimensional printing, smart materials, artificial intelligence-driven scaffold optimization, and organoid-based models, are introduced to help bridge the gap from preclinical research to successful clinical trials. In summary, ETE is transitioning from an experimental advancement to a translational reality by integrating significant achievements in biomaterials, fabrication technologies, and cell biology while following health regulatory standards. These efforts aim to provide regenerative solutions that overcome the limitations of current therapeutic approaches in clinical settings, ultimately facilitating healing and improving the patients' quality of life.
Renal failureKim Solez, Habba Mahal, Wisit Cheungpasitporn, Giuseppe Orlando
The purpose of this review is to summarize the most influential and conceptually significant publications from the past 2 years, including substantial 2026 publications, and to identify emerging directions likely to shape xenotransplantation and regenerative medicine in the near future. Advances in artificial intelligence (AI) now support more structured anticipation of future developments by integrating patterns across experimental, computational, and translational research. The field is approaching a potential inflection point in which increasingly capable AI systems, potentially approaching artificial general intelligence, may accelerate the design of stem-cell-derived tissues and progressively more complex organ constructs. In addition, scientific communication is evolving toward formats that support machine-assisted analysis and AI-driven knowledge synthesis. Multiple developments signal significant expansion across xenotransplantation and regenerative medicine, driven by innovations in gene editing, multimodal data integration, and AI-enabled prediction and decision-support systems. These advances will help to broaden access to transplantable organs and increase the scale and impact of the field across clinical practice, research, and workforce domains. Together, these trends suggest that AI-enabled regenerative and xenogeneic strategies may meaningfully reduce the organ shortage and support future progress toward precision-engineered organ replacement.
To address the need to both enrich stem cells and direct their osteogenic fate in bone tissue engineering and bone regeneration, we developed a stiffness-gradient hydrogel (~4.5-33 kPa) functionalized with a cell-enriching aptamer (Apt19s). This design forms a combined "enrich-and-differentiate" system: Apt19s actively enriches endogenous bone marrow-derived mesenchymal stem cells (BMSCs) at the scaffold site, while the osteoinductive high-stiffness niche (~33 kPa) directs their differentiation. Crucially, the combined cues produced an enhanced osteogenic outcome-evidenced by significantly greater alkaline phosphatase (ALP) activity (>2-fold increase), upregulated RUNX2/osteocalcin (OCN) gene expression (186.5% relative to control), and enhanced mineralization-that surpassed the additive effects of either cue presented independently. This integrated platform provides a practical strategy for developing cell-free osteogenic materials that actively tackle the dual challenges of endogenous cell sourcing and lineage-specific induction.
Complex tissue/organ regeneration is a well-orchestrated biological process that is orchestrated by the coordinated effort of neural, vascular and immune systems, accompanied by multiple cellular interactions and signal crosstalk. The beneficial pro-regenerative microenvironments are of great significance for regulating tissue-resident cell viability, migration and differentiation to direct tissue repair process. 3D bioprinting is an advanced biomanufacturing strategy that utilizes hydrogel-containing bioinks to fabricate cell-laden scaffolds, but they face the limitations of insufficient bioactivity. Inorganic biomaterials have been recognized as effective bioactive agents owing to their tunable chemical composition, topographical architectures, and physiochemical properties, which can overcome the limitation of printable hydrogel and broaden their potential biological applications. This review primarily focuses on the design of inorganic biomaterials-reinforced printable hydrogel for modulating regenerative microenvironments including neural, vascular, and immune regulation, as well as summarizes the recent progress of their applications for tissue and organ regeneration. It begins with an introduction of inorganic biomaterials augmenting the biophysical and the biochemical properties of 3D-printed hydrogel, especially highlighting the improvement of topographical cues, mechanical strength, external field responsiveness, and bioactive components release for regulating various tissue microenvironments. Subsequently, recent advancements of inorganic biomaterials-reinforced printable hydrogel in regenerating musculoskeletal system, skin, and cardiac tissues are systematically reviewed. Finally, current challenges and future perspectives in the development of inorganic biomaterials-reinforced printable hydrogel are proposed. This review may offer a novel insight for the design of novel bioinks in combination with inorganic biomaterials and printable hydrogel, which shows great potential for engineered biofabrication and complex tissue/organ regeneration.
We report an in situ light-mediated reinforcement strategy for spatial microvascular patterning. Laser-patterned stiff zones in AlgMA/fibrin hydrogels suppress capillary formation by >81%. A linear stiffness-density relationship (R2 > 0.78) enables predictable engineering of heterogeneous tissue architecture.
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgeryYueliang Zhu, Sihe Qin
Limb reconstruction has emerged as a unique and increasingly important discipline in modern medicine. Limb reconstruction refers to the systematic restoration of complex pathological conditions resulting from various injuries or diseases-such as tissue defects, infections, and deformities-using a combination of surgical and non-surgical approaches. Its technical framework is primarily based on microsurgery, the Ilizarov technique, cement-induced membrane technique (Masquelet technique), engineered tissue regeneration, soft tissue balancing and dynamic reconstruction, and modern prosthetics, supplemented by other surgical modalities including internal and external fixation, joint replacement, sports medicine, and wound management. Limb reconstruction surgery employs these techniques to systematically restore the structure, morphology, and function of the limb, representing a critical component of modern surgery. This discipline overcomes the fragmentation inherent in traditional subspecialty care, providing a definitive clinical pathway for limb reconstruction and serving as the last beacon of hope for salvaging damaged limbs.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyYiDi Sun, XinYue Guo, ZiXue He, YaXuan Cui, Dezhong Wen, Baigong Xue, LiSha Li
Skin aging is an intricate and multidimensional biological process driven by both endogenous and exogenous factors. It manifests as impaired skin structure and function, morphological alterations, and an elevated risk of associated disorders. Current skin antiaging therapies have made considerable advancements. However, notable challenges persist regarding safety, long-term efficacy, and delivery efficiency. These challenges have prompted the field of regenerative medicine to pursue more effective therapeutic strategies. Engineered exosomes (Exos) are nanoscale vesicles optimized through bioengineered strategies. They exhibit excellent biocompatibility, low immunogenicity, and a strong capability to deliver diverse bioactive molecules. Stem cell-derived exosomes (SC-Exos) represent ideal sources for engineered Exos. However, natural Exos are limited by low yield, insufficient drug-loading capacity, and poor targeting efficiency. To address these limitations, engineered strategies have been developed to enhance yield, enrich functional components, and achieve targeted delivery. Furthermore, this review investigates the combined use of engineered Exos with delivery systems such as microneedles and gels to enhance therapeutic efficacy. Ongoing technological advancements have enabled engineered Exos to emerge as a safe, efficient, precise, and promising frontier in precision skin antiaging. They are poised to drive revolutionary breakthroughs in regenerative medicine.
Communications biologyMohamed Saqawa, Miguel Vieira Coelho, Marta Lourenço, Claire Villette, David Barata, Lorenzo Apolloni, Silvia Panseri, A S Silva-Barroso, Rafaela Seabra, Diana…
Osteosarcoma (OS) is a highly aggressive bone malignancy that predominantly affects adolescents and young adults. Despite the progress in conventional treatment approaches, such as surgery and chemotherapy, patient outcomes remain poor due to OS metastatic potential, chemoresistance and frequent recurrence. Although recent advancements in novel therapeutic strategies, such as molecular inhibitors, gene-based interventions, alongside immuno- and radiotherapies, have emerged in recent years, OS is still not well understood due to its complexity and heterogeneity. Tissue engineering and predictive preclinical models offer a good toolbox to study OS and produce patient-tailored therapeutic protocols. This review discusses the recent development of tissue engineering-based strategies and OS mimicking preclinical models like 3D in vitro models, organ-on-chip technologies, and predictive computational (in silico) models, ranging from mechanistic (white-box) to data-driven (black-box) and hybrid (grey-box) approaches. Based on these recent developments, researchers can better replicate the native OS tumour microenvironment, which opens the doors to a more representative high-throughput drug screening tools and patient-tailored treatment strategies.
Synthetic biology can program cellular behavior but remains underused in regenerative medicine. This commentary argues that integrating synthetic biology with tissue engineering should target vascularization and immune integration through compact, context-aware circuits. Embedded within engineered tissues, these circuits could enable adaptive grafts that sense stress and coordinate regenerative responses.
BACKGROUND: Keratocyte cells residing in the corneal stroma produce extracellular matrix (ECM) proteins and support transparency. These cells are pivotal for corneal regeneration and the development of in vitro tissue substitutes. However, there is limited literature on the characteristics of primary and immortalized keratocyte cells. METHODS AND RESULTS: This study investigates the preservation of keratocyte phenotype in primary cells isolated from human donors and their subsequent immortalized passages. Primary human corneal keratocyte cells (hKCs) isolated from donor corneas were immortalized using SV40. The differentiated expression of corneal and limbal genes in both primary hKC (at passage 2) and immortalized hKCs (at passages 9, 12, and 15) were evaluated using RT-PCR. Additionally, cells were examined using immunocytochemistry (ICC) with corneal keratocyte markers. The results demonstrate the presence of myofibroblast transformation in primary hKCs, while keratocyte characteristics remain intact even in subsequent passages of immortalized cells. The highest aquaporin 1 (AQP1), aldehyde dehydrogenase-3A1 (ALDH3A1), and collagen type I (COL1) expression was observed in immortalized hKC at passage 12. CONCLUSIONS: These findings suggest that immortalized corneal keratocytes, are a viable source for corneal tissue engineering studies, particularly up to passage 12. The isolation, characterization, and immortalization of corneal keratocytes are imperative for further research and applications. Knowing the characteristics of keratocyte cells used in tissue engineering and therapeutic studies will significantly impact the outcomes.
Chembiochem : a European journal of chemical biologyYichi Zhang, Ning Zhang, Linkai Jiang, Zhilong Zhou, Yuwei Zhang, Yuwen Wang, Yiting Lei, Ning Hu, Zhong Alan Li
As an emerging microphysiological system, organ-on-a-chip (OoC) replicates human organ structures and functions through microfabrication, holding promise as novel platforms for drug screening, disease modeling, and toxicity testing, although their broad application still faces significant validation challenges. This review systematically examines biomimetic scaffold selection strategies in OoC systems, with a focus on hydrogels, hydrogel microspheres, and other scaffold types. It details chip fabrication processes, including design concepts, material selection, microfabrication technology, and cell sources. By comparing physicochemical properties, biocompatibility, and functional characteristics of different materials, this paper explores optimal scaffold strategies for specific organ simulations. Based on comprehensive analysis, hydrogel scaffolds have become widely adopted for OoC construction due to their excellent biocompatibility and extracellular matrix-like properties. Synthetic polymers and bioceramic scaffolds demonstrate significant value in meeting specific mechanical requirements and constructing complex microstructures. As a novel hydrogel form, hydrogel microspheres exhibit considerable potential in dynamic culture simulation and drug delivery owing to their high specific surface area and controllable release capabilities. This paper also discusses future directions, including personalized scaffold design, intelligent responsive materials, and multiorgan coupling systems, providing theoretical guidance for advancing OoC technology.
ACS applied bio materialsJunzhou Tian, Bin He, Yuwei Li, Ji Zhang, Lin Zhong, Haodong Peng, Tao Jing, Zhongtao Li, Feng Lin, Jie Weng, Xiong Xiong, Shuxin Qu
Digital light processing (DLP) 3D printing of calcium phosphate (CaP) scaffolds tailored to fit personalized bone defects represents a promising strategy for bone tissue engineering. However, conventional CaP-GelMA inks suffer from particle-induced ink heterogeneity and reduced photopolymerization efficiency, resulting in poor printability. Additionally, since CaP crystallizes before polymer crosslinking, it only mixes with the GelMA matrix, leading to weak interfacial interactions between them and poor mechanical properties of the scaffold. To overcome these challenges, traditional calcium phosphate (CaP) particles were replaced with highly water-soluble calcium phosphate oligomers (CPO), which provide superior dispersion and minimal light scattering leading to high printability. More importantly, the organic-inorganic hybrid structure within the scaffold was achieved through concurrent GelMA crosslinking and CPO crystallization. The optimal CPO, with a Ca/P ratio of 1.67, demonstrated favorable DLP printability owing to its low and narrowly distributed particle size, high solid content, and low absorbance of light. Among various formulations, the ink containing 20% CPO (GC-20) exhibited superior printability and structural integrity. Characterization confirmed that CPO converts to hydroxyapatite (HAp) and forms hybrid HAp-GelMA structures during DLP printing, resulting in significantly improved compressive modulus and toughness. In vitro assays indicated that the scaffolds are noncytotoxic, promote cell adhesion and proliferation, and substantially enhance osteogenic differentiation and mineralization of mesenchymal stem cells. These findings highlight the potential of CPO-based DLP inks for applications in personalized bone and cartilage regeneration.
ACS applied bio materialsChithra Anilkumar, Anjaneyulu Udduttula
Osteoarthritis (OA) is a rapidly growing joint disease worldwide, and its chronic and progressive form can cause damage to the cartilage and subchondral bone, resulting in physical and economic suffering for affected individuals. So far, potential therapeutic approaches, such as systematic drug administration and intraarticular injections, have been used to treat OA and regenerate osteochondral defects, but they are palliative rather than curative. Thus, hydrogels with biologics (matrix-degrading enzyme inhibitors) and small molecules (growth factors, anti-inflammatory molecules) show promising results in preclinical studies but have failed in clinical practice due to inadequate patient benefits. Recently, bioinks have gained significant attention as regenerative biomaterials in tissue engineering due to their ability to contain cells and bioactive small molecules, such as proteins, peptides, and growth factors. Bioinks are developed using various polymers with crosslinkers. The crosslinkers play a crucial role in the formation of bioinks, which can be natural or synthetic (ionic, chemical, photo, etc.). However, extensive usage of crosslinkers limits the clinical application of bioinks due to compromising the ideal properties of bioinks, such as cytocompatibility, biodegradability, and biomechanical properties. Therefore, the potential solution to this problem is utilizing the click chemistry approach. The click chemistry strategy can achieve efficient bio-inks without compromising their intrinsic and optimal characteristics, as click reactions are rapid, spontaneous, and bioorthogonal, favoring the gelation time, rate of degradation, and cell viability. A few reports have delivered thorough information on click chemistry-induced hydrogels and bioinks for bone regeneration, but they are not specific to osteochondral regeneration. This review addresses this gap by exploring the fundamental concepts, challenges, and prospects of click chemistry, specifically its distinct click reactions, in developing bioinks and 3D bioprinting scaffolds for OA treatment and osteochondral regeneration. Furthermore, it addresses regulatory and clinical hurdles tied to bioink translation, providing an integrative overview of translational bioinks and tissue engineering strategies for cartilage and osteochondral regeneration.
Proceedings of the National Academy of Sciences of the United States of AmericaSina Kheiri, Jessica Shah, Peiyuan Chai, Shashaank A Venkatesh, Ryan A Flynn, Roger D Kamm, Ritu Raman
Engineering organized microvascular networks remains a critical challenge in tissue engineering and regenerative medicine. While biochemical approaches for patterning angiogenesis via growth factor delivery have shown promise, their inability to pattern sustained growth factors with spatiotemporal control limits effectiveness. Here, we demonstrate that dynamically patterned mechanical forces enable precise spatiotemporal control over angiogenic sprouting. We developed a magnetically actuated human vessel-on-a-chip platform that integrates a perfusable endothelialized microchannel within a collagen matrix and allows noninvasive and tunable mechanical stimulation across three spatial dimensions and time (4D). Using an automated 3-axis actuator, we systematically investigated how strain magnitude, frequency, and direction modulate endothelial cell behavior and vessel morphogenesis. Dynamic mechanical stimulation at physiological strain magnitudes (5 to 15%) enhanced endothelial alignment and barrier function while promoting angiogenesis in a strain magnitude-dependent manner: lower dynamic strain (5%) maximized sprout initiation, whereas higher dynamic strain (15%) promoted elongation of sprouts. Sequential reorientation of strain direction reprogrammed sprouting trajectories along X, Y, and Z directions, generating complex sprout geometries such as L-shaped branches. RNA sequencing revealed mechanically induced transcriptional profiles distinct from unstimulated controls, characterized by upregulation of genes associated with angiogenesis, mechanotransduction, and extracellular matrix remodeling. Functional perturbation of PIEZO1 reduced strain-induced sprouting without altering barrier function, indicating that dynamic mechanical stimulation engages multiple mechanotransduction pathways to regulate angiogenesis. Collectively, these findings establish a strategy for spatiotemporally controlled angiogenesis through 4D force patterning to program vascular morphogenesis while preserving function. This approach provides a foundation for engineering hierarchically organized vascular networks for tissue regeneration.
ACS applied bio materialsCai Ling Yong, Alexander Shao-Rong Pang, Dinesh Kumar Srinivasan
Plastic and reconstructive surgery (PRS) aims to restore form and function, thereby improving patients' quality of life. In recent years, nanotechnology has emerged as a promising field, offering innovative solutions in tissue engineering, wound healing, implant design, and aesthetic applications. This scoping review evaluates recent advancements, clinical applications, and limitations of nanotechnology-based approaches in plastic surgery. A structured literature search was conducted in PubMed using combinations of keywords including "nanotechnology", "nanoparticles", "plastic surgery", "reconstructive surgery", "wound healing", "tissue engineering", and "aesthetic medicine", combined using Boolean operators (AND/OR). Example search string: ("nanotechnology" OR "nanoparticles" OR "nanomedicine") AND ("plastic surgery" OR "reconstructive surgery" OR "wound healing" OR "tissue engineering" OR "aesthetic medicine"). Inclusion criteria included English-language articles published within the past five years focusing on nanotechnology applications in PRS. Reviews, preclinical studies, and clinical studies were included. Editorials, conference abstracts, and studies not directly relevant were excluded. Key data were extracted, including nanomaterial types, methods of application, and reported therapeutic outcomes, and findings were synthesized through thematic analysis. This review identified diverse nanotechnology applications, including nanoskin development, nanoparticle-mediated drug delivery, nanoscaffolds for tissue regeneration, and improved biomaterials for reconstructive procedures such as breast reconstruction. Notable innovations included enhanced wound healing outcomes using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-based approaches, burn treatment using tilapia skin xenografts, and chitosan-based nanoparticles demonstrating antimicrobial activity and drug delivery potential. Despite promising preclinical and early clinical results, widespread clinical translation remains limited. Key barriers include insufficient long-term safety and toxicity data, challenges in large-scale production, and regulatory constraints. Nanotechnology in Plastic and Reconstructive Surgery. Created in BioRender. Yong, C.L. (2026) https://BioRender.com/l1pmh1n.
BiomacromoleculesTongtong Cui, Azra Kocaarslan, Yosuke Akae, Patrick Théato
Articular cartilage (AC) defects can lead to joint destruction and osteoarthritis, necessitating immediate intervention to prevent progressive cartilage degeneration. To support cartilage repair, hydrogels have been explored due to their structural similarity to the extracellular matrix (ECM), offering a hydrated microenvironment for chondrocytes that promotes cell adhesion and proliferation. Polyurethane (PU) is a promising candidate with adjustable mechanical properties, high biocompatibility, and degradability. Given the advantages of both hydrogels and PU for biomedical applications, functional degradable PU hydrogels present a potential solution for cartilage regeneration. This review summarizes the structure-property relationship and degradation mechanisms of PU hydrogels. Their advanced functionalities in cartilage repair are highlighted, including anti-inflammatory and antibacterial properties, controlled drug delivery, injectability, self-healing, and stimulus responsiveness. By reviewing recent advances and emerging technologies, this review provides valuable insights and a future outlook for the development of next-generation cartilage repair materials.
Four-dimensional (4D) printing offers a promising strategy for fabricating shape-adaptive bone scaffolds capable of conforming to complex defect geometries; however, achieving stable fabrication, homogeneous dispersion of multifunctional components, and predictable osteogenic performance remains challenging. In this study, a solvent-free resonant acoustic mixing (RAM)-assisted strategy was introduced to fabricate fused deposition modeling (FDM)-printed shape memory P(DLLA-TMC)/β-tricalcium phosphate (β-TCP)/polydopamine (PDA) composite scaffolds. RAM enabled uniform dispersion of microscale β-TCP and nanoscale PDA within the polymer matrix under low-shear conditions, providing a robust basis for continuous filament extrusion and FDM-based 4D printing. The resulting ternary composite scaffolds exhibited suitable rheological behavior, improved compressive strength, enhanced surface hydrophilicity, and stable near-infrared-triggered photothermal shape memory performance. In vitro experiments demonstrated excellent cytocompatibility and significantly enhanced osteogenic differentiation, as evidenced by increased alkaline phosphatase activity, mineralized matrix deposition, and upregulated osteogenesis-related gene and protein expression. Furthermore, in vivo rat calvarial defect models confirmed that the composite scaffolds effectively promoted new bone formation and structural maturation. Collectively, this work establishes an integrated material-process-function framework for the scalable fabrication of multifunctional 4D-printed bone scaffolds and highlights the translational potential of RAM-assisted manufacturing for advanced bone tissue engineering applications.
Physical medicine and rehabilitation clinics of North AmericaAnthony J Loffredo, George C Chang Chien, Sanjog S Pangarkar
This article reviews 6 categories of regenerative therapies for chronic pain, including cell-based therapies, biologics, gene therapy, exosomes, tissue engineering, and biophysical stimuli. While mesenchymal stem cells, bone marrow aspirate concentrate, and adipose-derived stem cells show promise for mild conditions like knee osteoarthritis and lateral epicondylitis, no regenerative therapy is Food and Drug Administration (FDA)-approved for chronic pain. Platelet-rich plasma and autologous conditioned serum are not FDA-approved as stand-alone treatments. Clinical guidance includes holding nonsteroidal anti-inflammatory drugs, avoiding cytotoxic anesthetics, and managing expectations. The article highlights legal risks related to biologics and stresses need for standardized protocols and high-quality trials.