Search Results (119)

The evolving paradigm of precision medicine is redefining the landscape of orthobiologic therapies by moving beyond traditional diagnosis-driven approaches toward biologically tailored interventions. This review synthesizes current evidence supporting precision orthobiologics, emphasizing the significance of individualized treatment strategies in musculoskeletal regenerative medicine. This narrative review synthesized literature from PubMed, Embase, and Web of Science databases (January 2015–December 2024) using search terms, including ‘precision medicine,’ ‘orthobiologics,’ ‘regenerative medicine,’ ‘biomarkers,’ and ‘artificial intelligence’. Biological heterogeneity among patients with ostensibly similar clinical diagnoses—reflected in diverse inflammatory states, genetic backgrounds, and tissue degeneration patterns—necessitates patient stratification informed by molecular, genetic, and multi-omics biomarkers. These biomarkers not only enhance diagnostic accuracy but also improve prognostication and monitoring of therapeutic responses. Advanced imaging modalities such as T2 mapping, DTI, DCE-MRI, and molecular PET offer non-invasive quantification of tissue health and regenerative dynamics, further refining patient selection and treatment evaluation. Simultaneously, bioengineered delivery systems, including hydrogels, nanoparticles, and scaffolds, enable precise and sustained release of orthobiologic agents, optimizing therapeutic efficacy. Artificial intelligence and machine learning approaches are increasingly employed to integrate high-dimensional clinical, imaging, and omics datasets, facilitating predictive modeling and personalized treatment planning. Despite these advances, significant challenges persist—ranging from assay variability and lack of standardization to regulatory and economic barriers. Future progress requires large-scale multicenter validation studies, harmonization of protocols, and cross-disciplinary collaboration. By addressing these limitations, precision orthobiologics has the potential to deliver safer, more effective, and individualized care. This shift from generalized to patient-specific interventions holds promise for improving outcomes in degenerative and traumatic musculoskeletal disorders through a truly integrative, data-informed therapeutic framework. Full article

Traditional polyurethanes have gained widespread application due to their excellent mechanical properties, wear resistance, and processability. However, these materials are susceptible to cracking or fracture under environmental stresses. In recent years, self-healing polyurethanes have garnered significant attention as a critical research field owing to their key capabilities, such as repairing physical damage, restoring mechanical strength, structural adaptability, and cost-effective manufacturing. This review systematically examines the healing mechanisms, structural characteristics, and performance metrics of self-healing polyurethanes, with in-depth analysis of their repair efficacy across various applications—particularly in flexible electronic devices. It demonstrates that self-healing polyurethanes overcome traditional failure modes in flexible electronics through self-repair-function integration mechanisms. Their stimuli-responsive healing behavior is driving the evolution of this field toward an intelligent regenerative electronics paradigm. Full article

The transition from three-dimensional (3D) to four-dimensional (4D)-bioprinting marks a significant advancement in tissue engineering and drug delivery. 4D-bioprinting offers the potential to more accurately mimic the adaptive qualities of living tissues due to its dynamic flexibility. Structures created with 4D-bioprinting can change shape in response to internal and external stimuli. This article reviews the background, key concepts, techniques, and applications of 4D-bioprinting, focusing on its role in tissue scaffolding and drug delivery. We discuss the limitations of traditional 3D-bioprinting in providing customized and sustained medication release. Shape memory polymers and hydrogels are examples of new responsive materials enabled by 4D-bioprinting that can enhance drug administration. Additionally, we provide a thorough analysis of various biopolymers used in drug delivery systems, including cellulose, collagen, alginate, and chitosan. The use of biopolymers in 4D-printing significantly increases material responsiveness, allowing them to react to stimuli such as temperature, light, and humidity. This capability enables complex designs with programmable shape and function changes. The expansion and contraction of hydrogels in response to temperature changes offer a practical method for controlled drug release. 4D-bioprinting has the potential to address significant challenges in tissue regeneration and medication administration, spurring ongoing research in this technology. By providing precise control over cell positioning and biomaterial integration, traditional 3D-bioprinting has evolved into 4D-bioprinting, enhancing the development of tissue constructs. 4D-bioprinting represents a paradigm shift in tissue engineering and biomaterials, offering enhanced possibilities for creating responsive, adaptive structures that address clinical needs. Researchers can leverage the unique properties of biopolymers within the 4D-printing framework to develop innovative approaches for tissue regeneration and drug delivery, leading to advanced treatments in regenerative medicine. One potential future application is in vivo tissue regeneration using bioprinted structures that can enhance the body’s natural healing capabilities. Full article

Osteochondral regeneration remains a major clinical challenge due to the complex architecture and biomechanical demands of the osteochondral unit. Bioactive hydrogels have emerged as promising materials capable of supporting repair through their capacity to mimic the extracellular matrix (ECM), enable cell encapsulation, and deliver bioactive cues. However, recent insights reveal that simply engineering hydrogels for structural and cellular support is insufficient. A new paradigm is emerging—one that embraces the complexity of the osteochondral niche by integrating immunomodulatory and mechanobiological cues into biomaterial design. In particular, the hydrogel’s capacity to modulate macrophage polarization and support the immunoregulatory function of mesenchymal stem cells (MSCs) is critical to orchestrate regenerative outcomes. Simultaneously, the mechanical properties of hydrogels—such as stiffness, porosity, and viscoelasticity—can profoundly influence stem cell fate and local tissue morphogenesis. This review discusses recent advances in hydrogel-based strategies for osteochondral repair, highlighting the interplay between immunological signals and the mechanical microenvironment, and calls for a shift from reductionist tissue-engineering approaches to systems-level design of tunable, immuno-mechanobiological microenvironments. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

The One Health paradigm—recognizing the interconnected health of humans, animals, and the environment—promotes the development of sustainable technologies that enhance human health while minimizing ecological impact. In this context, bio-based hydrogels have emerged as a promising class of biomaterials for advanced medical applications. Produced through biotechnological methods such as genetic engineering and microbial fermentation, these hydrogels are composed of renewable and biocompatible materials, including recombinant collagen, elastin, silk fibroin, bacterial cellulose, xanthan gum, and hyaluronic acid. Their high water content, structural tunability, and biodegradability make them ideal candidates for various biomedical applications such as wound healing, tissue regeneration, and the design of extracellular matrix (ECM)-mimicking scaffolds. By offering controlled mechanical properties, biocompatibility, and the potential for minimally invasive administration, sustainable hydrogels represent a strategic innovation for regenerative medicine and therapeutic interventions. This review discusses the characteristics and medical applications of these hydrogels, highlighting their role in advancing sustainable healthcare solutions within the One Health framework. Full article

Spinal cord injury (SCI) remains one of the toughest obstacles in neuroscience and regenerative medicine due to both severe functional loss and limited healing ability. This article aims to provide a key integrative, mechanism-focused review of the molecular landscape of SCI and the new disruptive therapy technologies that are now evolving in the SCI arena. Our goal is to unify a fundamental pathophysiology of neuroinflammation, ferroptosis, glial scarring, and oxidative stress with the translation of precision treatment approaches driven by artificial intelligence (AI), CRISPR-mediated gene editing, and regenerative bioengineering. Drawing upon advances in single-cell omics, systems biology, and smart biomaterials, we will discuss the potential for reprogramming the spinal cord at multiple levels, from transcriptional programming to biomechanical scaffolds, to change the course from an irreversible degeneration toward a directed regenerative pathway. We will place special emphasis on using AI to improve diagnostic/prognostic and inferred responses, gene and cell therapies enabled by genomic editing, and bioelectronics capable of rehabilitating functional connectivity. Although many of the technologies described below are still in development, they are becoming increasingly disruptive capabilities of what it may mean to recover from an SCI. Instead of prescribing a particular therapeutic fix, we provide a future-looking synthesis of interrelated biological, computational, and bioengineering approaches that conjointly chart a course toward adaptive, personalized neuroregeneration. Our intent is to inspire a paradigm shift to resolve paralysis through precision recovery and to be grounded in a spirit of humility, rigor, and an interdisciplinary approach. Full article

Short bowel syndrome (SBS) is characterized by insufficient intestinal length to support absorption causing malnutrition. The bowel adapts to SBS via intestinal dilation and delayed gastric emptying but still often requires long-term parenteral nutrition. Current surgical options to lengthen the bowel pose significant risks and often provide limited expansion. ‘Distraction enterogenesis’ has been proposed as a technique to induce intestinal lengthening for SBS. The deployment of the intestinal expansion sleeve (IES) device is hypothesized to result in significant intestinal lengthening in vivo. A Roux-en-Y was created in the jejunum of seven rats for isolated IES deployment. The IES was precontracted over a Bucatini noodle and inserted into the isolated roux limb. After 4 weeks of deployment, rats were sacrificed, Roux-en-Y length recorded, and histology analyzed. A paired t-test was performed to compare initial and final roux limb lengths and histopathological tissue remodeling. Intestinal distraction evaluated at 4 weeks post deployment of the IES resulted in a significant 30.2% elongation in roux limb length (43.6 ± 14.4 mm to 56.4 ± 20.8 mm (p = 0.043, n = 7). IES samples showed changes in mucosal and submucosal integrity and bowel wall thickness in response to IES lengthening. In samples with partial mucosal erosion, the basal/regenerative layers of the mucosa were preserved. Distraction enterogenesis with significant intestinal lengthening in vivo has been achieved with the IES device. Histologic changes suggest all bowel functional layers and attributes are maintained through distraction enterogenesis. Future constructs of the IES may benefit from the addition of immunomodulators. Increasing intestinal mass with these devices may complement the treatment paradigm for SBS. Full article

Stem-cell behavior is governed not solely by intrinsic genetic programs but by highly specialized microenvironments—or niches—that integrate structural, biochemical, and mechanical cues to regulate quiescence, self-renewal, and differentiation. This review traces the evolution of stem-cell niche biology from foundational embryological discoveries to its current role as a central determinant in tissue regeneration and disease. We describe the cellular and extracellular matrix architectures that define adult stem-cell niches across diverse organs and dissect conserved signaling axes—including Wnt, BMP, and Notch—that orchestrate lineage commitment. Emphasis is placed on how aging, inflammation, fibrosis, and metabolic stress disrupt niche function, converting supportive environments into autonomous drivers of pathology. We then examine emerging therapeutic strategies that shift the regenerative paradigm from a stem-cell-centric to a niche-centric model. These include stromal targeting (e.g., FAP inhibition), which are engineered scaffolds that replicate native niche mechanics, extracellular vesicles that deliver paracrine cues, and composite constructs that preserve endogenous cell–matrix interactions. Particular attention is given to cardiac, hematopoietic, reproductive, and neurogenic niches, where clinical failures often reflect niche misalignment rather than intrinsic stem-cell deficits. We argue that successful regenerative interventions must treat stem cells and their microenvironment as an inseparable therapeutic unit. Future advances will depend on high-resolution niche mapping, mechanobiologically informed scaffold design, and niche-targeted clinical trials. Re-programming pathological niches may unlock regenerative outcomes that surpass classical cell therapies, marking a new era of microenvironmentally integrated medicine. Full article

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

Facial aging is a multifactorial and stratified biological process characterized by progressive morphological and biochemical alterations affecting both cutaneous (Layer I) and subcutaneous (Layer II) tissues. These age-related changes manifest clinically as volume depletion, tissue ptosis, and a decline in overall skin quality. In response to these phenomena, thread lifting techniques have evolved significantly—from simple mechanical suspension methods to sophisticated bioactive platforms. Contemporary threads now incorporate biocompatible polymers and hyaluronic acid (HA), aiming not only to reposition soft tissues but also to promote dermal regeneration. This review provides a comprehensive classification and critical assessment of thread lifting materials, focusing on their chemical composition, mechanical performance, degradation kinetics, and biostimulatory potential. Particular emphasis has been given to the surface integration of HA into monofilament threads, especially with the emergence of advanced delivery systems such as NAMICA, which facilitate sustained HA release. Advanced thread materials, especially those fabricated from poly(L-lactide-co-ε-caprolactone) [P(LA/CL)], demonstrate both tensile support and regenerative efficacy. Emerging HA-covered threads exhibit synergistic bioactivity, stimulating skin remodeling. NAMICA technology represents an advancement in the field, in which HA is encapsulated within biodegradable polymer fibers to enable gradual release and enhanced dermal integration. Nonetheless, well-designed human studies are still needed to substantiate its therapeutic efficacy. Consequently, the paradigm of thread lifting is shifting from purely mechanical interventions toward biologically active systems that promote comprehensive ECM regeneration. The integration of HA into resorbable threads, especially when combined with sustained-release technologies, represents a meaningful innovation in aesthetic dermatology, meriting further preclinical and clinical evaluation. Full article

Background and Objectives: Complete dentures remain a primary solution for oral rehabilitation in aging and medically compromised populations. The integration of digital workflows, regenerative materials, and smart technologies is propelling prosthodontics towards a new era, transcending the limitations of traditional static prostheses. Materials and Methods: This narrative review synthesizes historical developments, current practices, and future innovations in complete denture therapy. A comprehensive review of literature from PubMed, Scopus, and Web of Science (2000–2025) was conducted, with a focus on materials science, digital design, patient-centered care, artificial intelligence (AI), and sustainable fabrication. Results: Innovations in the field include high-performance polymers, CAD–CAM systems, digital impressions, smart sensors, and bioactive liners. Recent trends in the field include the development of self-monitoring prostheses, artificial intelligence (AI)-driven design platforms, and bioprinted regenerative bases. These advances have been shown to enhance customization, durability, hygiene, and patient satisfaction. However, challenges persist in terms of accessibility, clinician training, regulatory validation, and ethical integration of digital data. Conclusions: The field of complete denture therapy is undergoing a transition toward a new paradigm of prosthetics that are personalized, intelligent, and sustainable. To ensure the integration of these technologies into standard care, ongoing interdisciplinary research, clinical validation, and equitable implementation are imperative. Full article

Titanium alloy thin-walled components are extensively used in aerospace engineering, yet their milling stability remains a persistent challenge due to vibration-induced surface anomalies. This study develops an advanced dynamic model for the face milling of titanium alloy thin-walled structures, systematically integrating axial cutting dynamics with regenerative chatter mechanisms and nonlinear process damping phenomena. The proposed framework crucially accounts for time-varying tool–workpiece interactions and damping characteristics, enabling precise characterization of stability transitions under dynamically varying axial immersion conditions. A novel extension of the semi-discretization method is implemented to resolve multi-parameter stability solutions, establishing a computational paradigm for generating three-dimensional stability lobe diagrams (3D SLDs) that concurrently evaluate spindle speed, cutting position, and the axial depth of a cut. Comprehensive experimental validation through time-domain chatter tests demonstrates remarkable consistency between theoretical predictions and empirical chatter thresholds. The results reveal that process damping significantly suppresses chatter at low spindle speeds, while regenerative effects dominate instability at higher speeds. This work provides a systematic framework for optimizing machining parameters in thin-walled component manufacturing, offering improved accuracy in stability prediction compared to traditional two-dimensional SLD methods. The proposed methodology bridges the gap between theoretical dynamics and industrial applications, facilitating efficient high-precision machining of titanium alloys. Full article

Multimodal artificial intelligence (AI) is driving a paradigm shift in modern biomedicine by seamlessly integrating heterogeneous data sources such as medical imaging, genomic information, and electronic health records. This review explores the transformative impact of multimodal AI across three pivotal areas: biomaterials science, medical diagnostics, and personalized medicine. In the realm of biomaterials, AI facilitates the design of patient-specific solutions tailored for tissue engineering, drug delivery, and regenerative therapies. Advanced tools like AlphaFold have significantly improved protein structure prediction, enabling the creation of biomaterials with enhanced biological compatibility. In diagnostics, AI systems synthesize multimodal inputs combining imaging, molecular markers, and clinical data—to improve diagnostic precision and support early disease detection. For precision medicine, AI integrates data from wearable technologies, continuous monitoring systems, and individualized health profiles to inform targeted therapeutic strategies. Despite its promise, the integration of AI into clinical practice presents challenges such as ensuring data security, meeting regulatory standards, and promoting algorithmic transparency. Addressing ethical issues including bias and equitable access remains critical. Nonetheless, the convergence of AI and biotechnology continues to shape a future where healthcare is more predictive, personalized, and responsive. Full article