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Keywords = orthopedic bioengineering

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35 pages, 1613 KB  
Review
Translational Progress and Clinical Challenges in Bioengineered Bone and Joint Repair
by Anoop Sunkara, Connor Primo McCloskey, David Antonio Dias, Siddhartha Kalala, Jack Thomas Peterson, Maxwell James Latshaw, Arun Kiran Movva and Albert Thomas Anastasio
Biomedicines 2026, 14(6), 1374; https://doi.org/10.3390/biomedicines14061374 - 18 Jun 2026
Abstract
Musculoskeletal disorders involving bone, cartilage, tendon, and joint tissues represent a leading cause of disability worldwide, and conventional surgical and graft-based interventions are limited by donor site morbidity, incomplete integration, and finite durability. Despite substantial preclinical progress, translation into reliable clinical benefit has [...] Read more.
Musculoskeletal disorders involving bone, cartilage, tendon, and joint tissues represent a leading cause of disability worldwide, and conventional surgical and graft-based interventions are limited by donor site morbidity, incomplete integration, and finite durability. Despite substantial preclinical progress, translation into reliable clinical benefit has remained inconsistent. This narrative review synthesizes recent advances in bioengineered approaches to bone and joint repair, emphasizing how materials design and regenerative strategy selection influence translational feasibility. Advances in scaffold-based systems highlight the role of material composition, architectural organization, and structure–function matching in supporting musculoskeletal regeneration. Regenerative platforms including stem cell therapies, extracellular matrix-derived constructs, and smart materials are evaluated for biological performance, manufacturability, and regulatory feasibility. Early translational and clinical studies demonstrate encouraging outcomes across selected musculoskeletal indications; however, variability in efficacy and adoption highlights persistent barriers to broader implementation. Key challenges include scalable manufacturing, cost and reimbursement uncertainty, and heterogeneity in clinical infrastructure, factors that may also influence access to advanced regenerative therapies. Future innovations should emphasize manufacturability and real-world evidence generation that align with practical clinical pathways. Full article
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26 pages, 780 KB  
Review
Next-Generation Biomaterials: Advanced Coatings and Smart Interfaces for Implant Technology: A Narrative Review
by Arun K. Movva, Michael O. Sohn, Connor P. McCloskey, Joshua M. Tennyson, Kishen Mitra, Samuel B. Adams and Albert T. Anastasio
Coatings 2026, 16(1), 87; https://doi.org/10.3390/coatings16010087 - 10 Jan 2026
Cited by 3 | Viewed by 1872
Abstract
Contemporary advances in bioengineering and materials science have substantially improved the viability of medical implants. The demand for optimized implant technologies has led to the development of advanced coatings that enhance biocompatibility, antimicrobial activity, and durability. Implant manufacturers and surgeons must anticipate both [...] Read more.
Contemporary advances in bioengineering and materials science have substantially improved the viability of medical implants. The demand for optimized implant technologies has led to the development of advanced coatings that enhance biocompatibility, antimicrobial activity, and durability. Implant manufacturers and surgeons must anticipate both biological and mechanical challenges when implementing devices for patient use. Key areas of concern include infection, corrosion, wear, immune response, and implant rejection; regulatory and economic considerations must also be addressed. Materials science developments are optimizing the integration of established materials such as biometrics, composites, and nanomaterials, while also advancing fabrication-based innovations including plasma functionalization, anodization, and self-assembled monolayers. Emerging smart and stimuli-responsive surface technologies enable controlled drug delivery and real-time implant status communication. These innovations enhance osseointegration, antimicrobial performance, and overall device functionality across orthopedic, dental, and cardiovascular applications. As implant design continues to shift toward personalized, responsive systems, advanced coating technologies are poised to deliver significantly improved long-term clinical outcomes for patients. Full article
(This article belongs to the Special Issue Advanced Coatings and Materials for Biomedical Applications)
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22 pages, 2073 KB  
Review
Advances in Fetal Repair of Spina Bifida Integrating Prenatal Surgery, Stem Cells, and Biomaterials
by Aleksandra Evangelista, Luigi Ruccolo, Valeria Friuli, Marco Benazzo, Bice Conti and Silvia Pisani
Biomedicines 2026, 14(1), 136; https://doi.org/10.3390/biomedicines14010136 - 9 Jan 2026
Cited by 1 | Viewed by 1830
Abstract
Spina bifida (SB) is a congenital malformation of the central nervous system (CNS), resulting from incomplete closure of the neural tube (NT) during early embryogenesis. Myelomeningocele (MMC), the most severe form of SB, leads to progressive neurological, orthopedic, and urological dysfunctions due to [...] Read more.
Spina bifida (SB) is a congenital malformation of the central nervous system (CNS), resulting from incomplete closure of the neural tube (NT) during early embryogenesis. Myelomeningocele (MMC), the most severe form of SB, leads to progressive neurological, orthopedic, and urological dysfunctions due to both NT developmental failure and secondary intrauterine injury (“two-hit hypothesis”). Prenatal repair of MMC has progressed considerably since the Management of Myelomeningocele Study (MOMS, 2011) trial, which showed that open fetal surgery can decrease the need for shunting and improve motor function, although it carries significant maternal risks. To address these limitations, minimally invasive techniques have been developed, with the goal of achieving similar benefits for the fetus while reducing maternal morbidity. Recent research has shifted toward regenerative strategies, integrating mesenchymal stem cells (MSCs), bioengineered scaffolds, and cell-derived products to move beyond mere mechanical protection toward true NT repair. Preclinical studies in rodent and ovine models have shown that amniotic- and placenta-derived MSCs exert neuroprotective and immunomodulatory paracrine effects, promoting angiogenesis, modulating inflammation, and supporting tissue regeneration. Minimally invasive, cell-based interventions such as Transamniotic Stem Cell Therapy (TRASCET), in preclinical rodent models, offer the possibility of very early treatment without hysterotomy, although translation remains limited by the lack of large-animal validation and long-term safety data. In parallel, advances in biomaterials, nanostructured scaffolds, and exosome-based therapies reinforce a regenerative paradigm that may improve neurological outcomes and quality of life in affected children. Ongoing translational studies are essential to optimize these approaches and define their safety and efficacy in clinical settings. This review provides an integrated overview of embryological mechanisms, diagnostic strategies, and prenatal therapeutic advances in SB treatment, with emphasis on prenatal repair, fetal surgery and emerging regenerative approaches. Full article
(This article belongs to the Special Issue Advances in Fetal Medicine and Neonatology)
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38 pages, 3935 KB  
Review
Three-Dimensional (3D) Printing Scaffold-Based Drug Delivery for Tissue Regeneration
by Maryam Aftab, Sania Ikram, Muneeb Ullah, Abdul Wahab and Muhammad Naeem
J. Manuf. Mater. Process. 2026, 10(1), 9; https://doi.org/10.3390/jmmp10010009 - 26 Dec 2025
Cited by 1 | Viewed by 2321
Abstract
Tissue regeneration is essential for wound healing, organ function restoration, and overall patient recovery. Its success significantly impacts medical procedures in fields like internal medicine and orthopedics, enhancing patient quality of life. Recent advances in regenerative medicine, particularly the combination of advanced drug [...] Read more.
Tissue regeneration is essential for wound healing, organ function restoration, and overall patient recovery. Its success significantly impacts medical procedures in fields like internal medicine and orthopedics, enhancing patient quality of life. Recent advances in regenerative medicine, particularly the combination of advanced drug delivery systems (DDS) and bioengineering, have enabled customized methods to improve tissue regeneration outcomes. However, conventional tissue engineering techniques have drawbacks, often using static scaffolds that lack the dynamic properties of real tissues, leading to subpar healing outcomes. The use of 3D printing and other advanced scaffolding techniques allows for the creation of bio functional scaffolds that deliver bioactive molecules at precise locations and times. The optimal integration of biological systems with enhanced material properties for personalized treatment options remains unclear. There is a need for more research into the complex interactions between cellular biology, drug delivery, and material technology to improve tissue regeneration. Despite progress in developing bioactive scaffolds and localized drug delivery methods, the interactions among different scaffold materials, bioactive agents, and cellular behaviors within the regenerative ecosystem are not fully understood. While there is extensive research on 3D-printed scaffolds in tissue engineering, there is a lack of studies integrating bio printing with in vivo biological reactions in real time. Limited research on the dynamic integration of patient-specific parameters in regeneration methods highlights the need for customized approaches that consider individual physiological differences and the complex biological environment at injury sites. Additionally, challenges arise when translating laboratory results into effective therapeutic applications, underscoring the necessity for interdisciplinary collaboration and innovative design approaches that align advanced material properties with biological needs. Full article
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24 pages, 564 KB  
Review
Arthroscopic Management of Patellar Instability in Skeletally Immature Patients: Current Concepts and Future Directions
by Alexandria Mallinos and Kerwyn Jones
J. Clin. Med. 2025, 14(19), 7085; https://doi.org/10.3390/jcm14197085 - 7 Oct 2025
Viewed by 1619
Abstract
Background/Objectives: Patellar instability is a common orthopedic condition affecting pediatric and adolescent populations, particularly during periods of rapid growth and increased sports participation. Recurrent patellar dislocation in skeletally immature patients is frequently associated with underlying anatomical risk factors such as patella alta, [...] Read more.
Background/Objectives: Patellar instability is a common orthopedic condition affecting pediatric and adolescent populations, particularly during periods of rapid growth and increased sports participation. Recurrent patellar dislocation in skeletally immature patients is frequently associated with underlying anatomical risk factors such as patella alta, trochlear dysplasia, or increased tibial tubercle–trochlear groove distance. Methods: This narrative review summarizes the current evidence on the epidemiology, diagnostic approach, and arthroscopic management of patellar instability in skeletally immature patients. Results: Arthroscopy has become an essential tool in both the diagnosis and treatment of patellar instability, allowing for minimally invasive assessment of patellofemoral alignment, chondral pathology, and ligament integrity. It also enables precise surgical interventions such as physeal-sparing medial patellofemoral ligament reconstruction, which remains the preferred stabilization technique for patients with open physes due to its safety and efficacy. Emerging innovations, including robotic-assisted tunnel placement, bioengineered scaffolds for cartilage repair, and three-dimensional modeling for surgical planning, have the potential to improve outcomes and arthroscopic surgical precision in this population. Despite these advances, major challenges such as a lack of pediatric-specific outcome measures, variability in surgical indications and rehabilitation protocols, and limited long-term follow-up data remain. Conclusions: Optimizing outcomes in pediatric and adolescent patients with patellar instability requires individualized growth-aware strategies and multidisciplinary collaborations. By integrating technological innovation with patient-centered care, clinicians can continue to refine the arthroscopic management of patellofemoral instability in young patients. Full article
(This article belongs to the Special Issue Clinical Application of Knee Arthroscopy)
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15 pages, 264 KB  
Review
Current Applications and the Future of Phage Therapy for Periprosthetic Joint Infections
by Arian Ocean Abedi, Armita Armina Abedi, Tristan Ferry and Mustafa Citak
Antibiotics 2025, 14(6), 581; https://doi.org/10.3390/antibiotics14060581 - 6 Jun 2025
Cited by 8 | Viewed by 6643
Abstract
Periprosthetic joint infections (PJI) present significant challenges in orthopedic surgery, largely due to the complexity of treating antibiotic-resistant infections. Phage therapy, which utilizes bacteriophages to target bacterial pathogens, offers a promising supplement to traditional antimicrobial methods. This review discusses the current applications of [...] Read more.
Periprosthetic joint infections (PJI) present significant challenges in orthopedic surgery, largely due to the complexity of treating antibiotic-resistant infections. Phage therapy, which utilizes bacteriophages to target bacterial pathogens, offers a promising supplement to traditional antimicrobial methods. This review discusses the current applications of phage therapy in the management of PJI, exploring its underlying mechanisms, clinical outcomes, and practical considerations. We also explore advances in phage therapy technology, including the development of phage cocktails, bioengineered phages, and combination therapies with antibiotics, which enhance the specificity and effectiveness of treatments. Furthermore, we address the future potential of phage therapy to be integrated into standard treatment protocols, focusing on ongoing innovations and research areas.The regulatory and ethical aspects of phage therapy in clinical settings are also discussed. By offering a comprehensive evaluation of both the current state and prospects of phage therapy, this review aims to inform clinical practice and stimulate further research into this innovative treatment modality for PJI management. Full article
21 pages, 4080 KB  
Review
Integrating Artificial Intelligence in Orthopedic Care: Advancements in Bone Care and Future Directions
by Rahul Kumar, Kyle Sporn, Joshua Ong, Ethan Waisberg, Phani Paladugu, Swapna Vaja, Tamer Hage, Tejas C. Sekhar, Amar S. Vadhera, Alex Ngo, Nasif Zaman, Alireza Tavakkoli and Mouayad Masalkhi
Bioengineering 2025, 12(5), 513; https://doi.org/10.3390/bioengineering12050513 - 13 May 2025
Cited by 19 | Viewed by 8230
Abstract
Artificial intelligence (AI) is revolutionizing the field of orthopedic bioengineering by increasing diagnostic accuracy and surgical precision and improving patient outcomes. This review highlights using AI for orthopedics in preoperative planning, intraoperative robotics, smart implants, and bone regeneration. AI-powered imaging, automated 3D anatomical [...] Read more.
Artificial intelligence (AI) is revolutionizing the field of orthopedic bioengineering by increasing diagnostic accuracy and surgical precision and improving patient outcomes. This review highlights using AI for orthopedics in preoperative planning, intraoperative robotics, smart implants, and bone regeneration. AI-powered imaging, automated 3D anatomical modeling, and robotic-assisted surgery have dramatically changed orthopedic practices. AI has improved surgical planning by enhancing complex image interpretation and providing augmented reality guidance to create highly accurate surgical strategies. Intraoperatively, robotic-assisted surgeries enhance accuracy and reduce human error while minimizing invasiveness. AI-powered smart implant sensors allow for in vivo monitoring, early complication detection, and individualized rehabilitation. It has also advanced bone regeneration devices and neuroprosthetics, highlighting its innovation capabilities. While AI advancements in orthopedics are exciting, challenges remain, like the need for standardized surgical system validation protocols, assessing ethical consequences of AI-derived decision-making, and using AI with bioprinting for tissue engineering. Future research should focus on proving the reliability and predictability of the performance of AI-pivoted systems and their adoption within clinical practice. This review synthesizes recent developments and highlights the increasing impact of AI in orthopedic bioengineering and its potential future effectiveness in bone care and beyond. Full article
(This article belongs to the Section Biosignal Processing)
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22 pages, 7366 KB  
Article
Hybrid Hydrogels Augmented via Additive Network Integration (HANI) for Meniscal Tissue Engineering Applications
by Anthony El Kommos, Praveen Magesh, Samantha Lattanze, Andrew Perros, Fotios Andreopoulos, Francesco Travascio and Alicia Jackson
Gels 2025, 11(4), 223; https://doi.org/10.3390/gels11040223 - 21 Mar 2025
Cited by 2 | Viewed by 1724
Abstract
Orthopedic soft tissue injuries, such as those to the fibrocartilaginous meniscus in the knee, present a significant clinical challenge, impacting millions globally and often requiring surgical interventions that fail to fully restore mechanical function. Current bioengineered meniscal replacement options that incorporate synthetic and/or [...] Read more.
Orthopedic soft tissue injuries, such as those to the fibrocartilaginous meniscus in the knee, present a significant clinical challenge, impacting millions globally and often requiring surgical interventions that fail to fully restore mechanical function. Current bioengineered meniscal replacement options that incorporate synthetic and/or natural scaffolds have limitations in biomechanical performance and biological integration. This study introduces a novel scaffold fabrication approach, termed Hybrid Hydrogels Augmented via Additive Network Integration (HANI) with great potential for meniscal tissue engineering applications. HANI scaffolds combine cross-linked gelatin-based hydrogels with polycaprolactone (PCL) additive networks, created via Fused Deposition Modeling (FDM), to enhance mechanical strength and replicate the anisotropic properties of the meniscus. Custom Stereolithography (SLA)-printed molds ensure precise dimensional control and seamless incorporation of PCL networks within the hydrogel matrix. The mechanical evaluation of HANI scaffolds showed improvements in compressive stiffness, stress relaxation behavior, and load-bearing capacity, especially with circumferential and 3D PCL reinforcements, when compared to hydrogel scaffolds without additive networks. These findings highlight HANI’s potential as a cost-effective, scalable, and tunable scaffold fabrication approach for meniscal tissue engineering applications. Full article
(This article belongs to the Special Issue Gels: 10th Anniversary)
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16 pages, 1093 KB  
Article
Gait Analysis in Patients After Hemiepiphysiodesis Due to Valgus or Varus Knee Deformity
by Paweł Leyko, Monika Zaborska, Agnieszka Walczak, Łukasz Tomczyk, Marcin Pelc, Aleksander Mnich, Radosław Operacz and Piotr Morasiewicz
J. Clin. Med. 2025, 14(2), 444; https://doi.org/10.3390/jcm14020444 - 12 Jan 2025
Cited by 3 | Viewed by 2326
Abstract
Background: Developmental knee joint deformities are a common problem in pediatric orthopedics. Children with a valgus or varus deformity of the distal femur or the proximal tibia are commonly treated with hemiepiphysiodesis. Gait analysis in patients with lower limb deformities plays an important [...] Read more.
Background: Developmental knee joint deformities are a common problem in pediatric orthopedics. Children with a valgus or varus deformity of the distal femur or the proximal tibia are commonly treated with hemiepiphysiodesis. Gait analysis in patients with lower limb deformities plays an important role in clinical practice. The purpose of our study was to assess gait parameters in patients who underwent hemiepiphysiodesis procedures of the distal femur or proximal tibia due to a knee deformity and to compare them with those in healthy controls. Methods: We prospectively evaluated 35 patients (14 females and 21 males) after hemiepiphysiodesis and compared the results with a healthy control group (26 participants). Gait was analyzed with a G-Sensor device (BTS Bioengineering Corp., Quincy, MA, USA). We assessed the following gait parameters: gait cycle duration, step length, support phase duration, swing phase duration, double support duration, single support duration, cadence, velocity, and step length. We assessed these gait parameters in a group of patients before and after treatment with hemiepiphysiodesis. We compared the patients’ results before and after treatment to those of a healthy control group. The level of significance was set at p < 0.05. Results: The mean follow-up period was 13 months. There was no difference in the results of gait assessments in patients prior to and after treatment. The median step length was 47.09% in the treated limb after treatment and 54.01% in the intact limb (p = 0.018). There were no other differences in gait parameters in the treated limbs and the healthy, intact limbs in the patient group after treatment. There were no significant differences in the patients before and after treatment compared with those in the healthy control group in all gait parameters. Conclusions: Valgus or varus knee deformity correction with the use of hemiepiphysiodesis does not significantly improve preoperative gait parameters. The biomechanical outcomes of hemiepiphysiodesis in the treatment of valgus or varus knee deformity are good. We observed no differences in gait cycle duration, step length, support phase duration, swing phase duration, double support duration, single support duration, gait velocity, cadence, or step length between the experimental and healthy control groups. Full article
(This article belongs to the Section Orthopedics)
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10 pages, 1697 KB  
Article
Comparison of Chondrocyte Behaviors Between Silk Microfibers and Polycaprolactone Microfibers in Tissue Engineering and Regenerative Medicine Applications
by Guang-Zhen Jin
Bioengineering 2024, 11(12), 1209; https://doi.org/10.3390/bioengineering11121209 - 29 Nov 2024
Cited by 2 | Viewed by 1352
Abstract
Silk and polycaprolactone (PCL), derived from natural and synthetic sources, respectively, are suture materials commonly used in surgery. Beyond their application in sutures, they are also compelling subjects in regenerative medicine and tissue engineering. This study evaluated the effects of degummed silk microfibers [...] Read more.
Silk and polycaprolactone (PCL), derived from natural and synthetic sources, respectively, are suture materials commonly used in surgery. Beyond their application in sutures, they are also compelling subjects in regenerative medicine and tissue engineering. This study evaluated the effects of degummed silk microfibers compared to electrospun PCL microfibers of a similar diameter on chondrocyte behavior. The two types of microfibers were analyzed using scanning electron microscopy (SEM), real-time PCR, Western blotting, and DMMB analysis. The results demonstrated that the silk microfibers exhibited a higher proliferative cell rate over time compared to the PCL microfibers. Additionally, the expression of chondrogenic phenotypes was significantly upregulated, while the marker for hypertrophic chondrocytes—type X collagen—was downregulated in cell-laden silk microfibers compared to cell-laden PCL microfibers. These findings suggest that natural degummed silk microfibers may be a viable option for repairing damaged cartilage in the future of orthopedic surgery and bioengineering. Full article
(This article belongs to the Special Issue Tissue Engineering and Regenerative Medicine in Bioengineering)
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22 pages, 5777 KB  
Article
Advancing Adult-Acquired Flatfoot Deformity Treatment: Enhanced Biomechanical Support Through Graphene Oxide-Integrated Bioengineered Grafts Tested In Silico
by Sebastián Nieto, Mónica Gantiva-Díaz, María A. Hoyos, Yuliet Montoya, Juan C. Cruz and Christian Cifuentes-De la Portilla
J. Funct. Biomater. 2024, 15(11), 335; https://doi.org/10.3390/jfb15110335 - 9 Nov 2024
Cited by 1 | Viewed by 2389
Abstract
Adult-Acquired Flatfoot Deformity (AAFD) is a progressive orthopedic condition causing the collapse of the foot’s medial longitudinal arch, often linked with injuries to the plantar arch’s passive stabilizers, such as the spring ligament (SL) and plantar fascia. Conventional treatment typically involves replacing the [...] Read more.
Adult-Acquired Flatfoot Deformity (AAFD) is a progressive orthopedic condition causing the collapse of the foot’s medial longitudinal arch, often linked with injuries to the plantar arch’s passive stabilizers, such as the spring ligament (SL) and plantar fascia. Conventional treatment typically involves replacing the SL with synthetic material grafts, which, while providing mechanical support, lack the biological compatibility of native ligaments. In response to this shortcoming, our study developed an electrospun, twisted polymeric graft made of polycaprolactone (PCL) and type B gelatin (GT), enhanced with graphene oxide (GO), a two-dimensional nanomaterial, to bolster biomechanical attributes. The addition of GO aimed to match the native ligamentous tissue’s mechanical strength, with the PCL-GT-GO 2.0% blend demonstrating an optimal Young’s modulus of 240.75 MPa. Furthermore, the graft showcased excellent biocompatibility, evidenced by non-hemolytic reactions, suitable wettability and favorable platelet aggregation—essential features for promoting cell adhesion and proliferation. An MTT assay revealed cell viability exceeding 80% after 48 h of exposure, highlighting the potential of the graft as a regenerative scaffold for affected ligaments. Computational modeling of the human foot across various AAFD stages assessed the graft’s in situ performance, with the PCL-GT-OG 2.0% graft efficiently preventing plantar arch collapse and offering hindfoot pronator support. Our study, based on in silico simulations, suggests that this bioengineered graft holds significant promise as an alternative treatment in AAFD surgery, marking a leap forward in the integration of advanced materials science for enhanced patient care. Full article
(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))
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12 pages, 3293 KB  
Article
Repair of Rat Calvarial Critical-Sized Defects Using Heparin-Conjugated Fibrin Hydrogel Containing BMP-2 and Adipose-Derived Pericytes
by Gulshakhar Kudaibergen, Sholpan Mukhlis, Ainur Mukhambetova, Assel Issabekova, Aliya Sekenova, Madina Sarsenova, Abay Temirzhan, Murat Baidarbekov, Baurzhan Umbayev and Vyacheslav Ogay
Bioengineering 2024, 11(5), 437; https://doi.org/10.3390/bioengineering11050437 - 29 Apr 2024
Cited by 8 | Viewed by 3112
Abstract
The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. [...] Read more.
The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration. Full article
(This article belongs to the Special Issue Bone Tissue Engineering and Translational Research)
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30 pages, 2585 KB  
Review
Delivery of Growth Factors to Enhance Bone Repair
by Jacob R. Ball, Tara Shelby, Fergui Hernandez, Cory K. Mayfield and Jay R. Lieberman
Bioengineering 2023, 10(11), 1252; https://doi.org/10.3390/bioengineering10111252 - 26 Oct 2023
Cited by 16 | Viewed by 6338
Abstract
The management of critical-sized bone defects caused by nonunion, trauma, infection, malignancy, pseudoarthrosis, and osteolysis poses complex reconstruction challenges for orthopedic surgeons. Current treatment modalities, including autograft, allograft, and distraction osteogenesis, are insufficient for the diverse range of pathology encountered in clinical practice, [...] Read more.
The management of critical-sized bone defects caused by nonunion, trauma, infection, malignancy, pseudoarthrosis, and osteolysis poses complex reconstruction challenges for orthopedic surgeons. Current treatment modalities, including autograft, allograft, and distraction osteogenesis, are insufficient for the diverse range of pathology encountered in clinical practice, with significant complications associated with each. Therefore, there is significant interest in the development of delivery vehicles for growth factors to aid in bone repair in these settings. This article reviews innovative strategies for the management of critical-sized bone loss, including novel scaffolds designed for controlled release of rhBMP, bioengineered extracellular vesicles for delivery of intracellular signaling molecules, and advances in regional gene therapy for sustained signaling strategies. Improvement in the delivery of growth factors to areas of significant bone loss has the potential to revolutionize current treatment for this complex clinical challenge. Full article
(This article belongs to the Special Issue Advances in Enabling Technologies for Bone Tissue Engineering)
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33 pages, 20827 KB  
Article
Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification
by Virginie Philippe, Annick Jeannerat, Cédric Peneveyre, Sandra Jaccoud, Corinne Scaletta, Nathalie Hirt-Burri, Philippe Abdel-Sayed, Wassim Raffoul, Salim Darwiche, Lee Ann Applegate, Robin Martin and Alexis Laurent
Pharmaceutics 2023, 15(9), 2333; https://doi.org/10.3390/pharmaceutics15092333 - 16 Sep 2023
Cited by 4 | Viewed by 2805
Abstract
Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The [...] Read more.
Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols. Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
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15 pages, 1905 KB  
Perspective
The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States
by Kai-Uwe Lewandrowski, John C. Elfar, Zong-Ming Li, Benedikt W. Burkhardt, Morgan P. Lorio, Peter A. Winkler, Joachim M. Oertel, Albert E. Telfeian, Álvaro Dowling, Roth A. A. Vargas, Ricardo Ramina, Ivo Abraham, Marjan Assefi, Huilin Yang, Xifeng Zhang, Jorge Felipe Ramírez León, Rossano Kepler Alvim Fiorelli, Mauricio G. Pereira, Paulo Sérgio Teixeira de Carvalho, Helton Defino, Jaime Moyano, Kang Taek Lim, Hyeun-Sung Kim, Nicola Montemurro, Anthony Yeung and Pietro Novellinoadd Show full author list remove Hide full author list
J. Pers. Med. 2023, 13(5), 852; https://doi.org/10.3390/jpm13050852 - 18 May 2023
Cited by 24 | Viewed by 5974
Abstract
Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial [...] Read more.
Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management. Full article
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