Junming Zhang1,2,3, Dawei Zhang2, and Jiang Peng3*
Received: January 05, 2025; Published: September 22, 2025
*Corresponding author: Jiang Peng, Institute of Orthopedics, the Fourth Medical Center, Chinese PLA General Hospital, Beijing 100853, China
DOI: 10.26717/BJSTR.2025.63.009875
Osteonecrosis of the femoral head is a serious skeletal condition, and early to mid-stage treatment is crucial for improving patients’ quality of life. In recent years, tissue engineering repair techniques have emerged as a novel therapeutic approach for this condition. This paper aims to analyze the efficacy of tissue engineering repair techniques in the treatment of early to mid-stage osteonecrosis of the femoral head, exploring their mechanisms, clinical applications, and future directions. By synthesizing relevant studies, this review will provide valuable insights for clinicians engaged in the management of this challenging disease.
Keywords: Osteonecrosis of the Femoral Head; Tissue Engineering Repair Techniques; Early to Mid-Stage Treatment; Efficacy Analysis; Clinical Applications
Abbreviations: AVN: Avascular necrosis; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs; MSCs: Mesenchymal Stem Cells; iPSCs: Induced Pluripotent Stem Cells; FGF: Fibroblast Growth Factor; TGF-β: Transforming Growth Factor-Beta; VEGF: Vascular Endothelial Growth Factor; BMPs: Bone Morphogenetic Proteins; ECM: Extracellular Matrix
Avascular necrosis (AVN) of the femoral head, commonly referred to as femoral head necrosis, is a condition characterized by the death of bone tissue due to a lack of blood supply. This pathological process can lead to joint pain, dysfunction, and ultimately osteoarthritis if left untreated. The epidemiology of AVN indicates that it predominantly affects individuals between the ages of 30 and 50, with a higher prevalence observed in males. Notably, risk factors contributing to the development of AVN include corticosteroid use, alcohol consumption, trauma, and certain medical conditions such as sickle cell disease and Cushing’s syndrome [1,2]. Understanding the demographic and clinical characteristics of AVN is crucial for early diagnosis and intervention. In the early to mid-stages of AVN, patients often present with hip pain, which may be exacerbated by weight-bearing activities. As the condition progresses, symptoms can include limited range of motion and joint stiffness. Diagnostic criteria typically involve imaging modalities such as X-rays, MRI, and CT scans, which help visualize the extent of bone damage and guide treatment decisions [2]. Accurate and timely diagnosis is essential to prevent further deterioration of the femoral head and to facilitate appropriate therapeutic strategies. Traditional treatment methods for AVN, including non-steroidal anti- inflammatory drugs (NSAIDs), core decompression, and osteotomies, have shown limited efficacy, particularly in advanced stages of the disease [3,4]. These interventions often fail to restore normal blood flow to the affected area and may not address the underlying bone degeneration.
Consequently, there has been a growing interest in the application of tissue engineering techniques as a novel approach to repair and regenerate necrotic bone. Tissue engineering offers the potential to not only restore the structural integrity of the femoral head but also to enhance healing through the incorporation of biomaterials and stem cell therapies [5]. The purpose of this review is to explore the current understanding of AVN of the femoral head, including its epidemiology, clinical manifestations, and diagnostic standards. Furthermore, we aim to critically assess the limitations of traditional treatment methods and highlight the emerging role of tissue engineering in the management of this debilitating condition. This exploration is significant as it may pave the way for innovative therapeutic strategies that can improve patient outcomes and quality of life.
Basic Principles of Tissue Engineering Repair Surgery Tissue engineering repair surgery is a multidisciplinary approach that combines principles from biology, materials science, and engineering to restore or replace damaged tissues. This innovative field aims to create functional tissues by utilizing a combination of cells, biomaterials, and biological signals. Understanding the fundamental principles of tissue engineering is essential for developing effective strategies for tissue repair and regeneration.
Cell Sources and Selection: The choice of cell sources is critical in tissue engineering, as the type of cells used can significantly influence the success of the repair process. Various cell types can be employed, including stem cells, differentiated cells, and primary cells. Stem cells, particularly mesenchymal stem cells (MSCs), have gained prominence due to their ability to differentiate into multiple lineages and their immunomodulatory properties, making them suitable for various applications in tissue engineering [6]. Additionally, the microenvironment in which these cells are cultured can affect their behavior, necessitating the selection of appropriate culture conditions and scaffolds that support cell viability and function [7]. The use of autologous cells is often preferred to minimize immune rejection, but allogeneic sources are also utilized, particularly when autologous cells are not available or sufficient. Recent advancements in cell sourcing, such as the use of induced pluripotent stem cells (iPSCs), provide additional avenues for generating patient-specific cells for tissue engineering applications [8].
Selection and Application of Biomaterials: Biomaterials play a pivotal role in tissue engineering, serving as scaffolds that provide structural support for cell attachment, proliferation, and differentiation. The selection of appropriate biomaterials is guided by several factors, including biocompatibility, biodegradability, mechanical properties, and the ability to promote cell adhesion and growth [9]. Natural polymers, such as collagen and chitosan, are often favored for their inherent biological activity and compatibility with living tissues [10]. Synthetic polymers, like poly (lactic acid) and polycaprolactone, offer tunable mechanical properties and degradation rates, enabling customization for specific applications [11]. Recent innovations have led to the development of hybrid biomaterials that combine the advantages of both natural and synthetic materials, enhancing their performance in tissue engineering [12]. Additionally, the incorporation of bioactive molecules into biomaterials can further enhance their functionality, promoting specific cellular responses and tissue integration [13].
Role of Growth Factors and Biological Signals: Growth factors and biological signals are crucial for orchestrating cellular behavior during tissue repair and regeneration. These molecules can influence cell proliferation, differentiation, and extracellular matrix production, thereby playing a significant role in the healing process [14]. Various growth factors, such as fibroblast growth factor (FGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), are commonly used in tissue engineering applications to enhance tissue formation and vascularization [15]. The delivery of these factors can be accomplished through various methods, including the use of controlled-release systems or incorporation into scaffolds, allowing for sustained release at the site of injury [16]. Understanding the signaling pathways activated by these growth factors is essential for optimizing their use in tissue engineering, as the timing and concentration of growth factor application can significantly impact the outcomes of tissue regeneration [17]. Integrating growth factors with biomaterials and cells in a synergistic manner can lead to improved tissue engineering strategies and better clinical outcomes.
Current Clinical Applications of Tissue Engineering Repair Techniques
Research Progress at Home and Abroad: The field of tissue engineering has witnessed significant advancements both domestically and internationally, reflecting a growing interest in regenerative medicine. In recent years, researchers have focused on developing innovative biomaterials and techniques to enhance tissue repair and regeneration. For instance, the use of organoids in engineering has shown promise for biofunctional reconstruction, allowing for the generation of complex tissue structures that mimic native organs [18]. Additionally, the endogenous repair theory has enriched strategies for orthopaedic biomaterials, suggesting that harnessing the body’s natural healing processes can lead to improved outcomes in tissue repair [19]. Furthermore, the development of advanced nanocomposite hydrogels for cartilage tissue engineering has highlighted the potential of new materials to support cellular functions and promote tissue integration [20]. These advancements underscore a collaborative global effort to refine tissue engineering applications, with ongoing studies exploring the regulatory challenges and therapeutic potentials of engineered tissues [21].
Comparison and Effectiveness Analysis of Different Techniques: A comparative analysis of various tissue engineering techniques reveals a spectrum of effectiveness depending on the specific application and tissue type. For example, cell sheet-based engineering has emerged as a promising method for bone regeneration, demonstrating superior biocompatibility and functional outcomes compared to traditional scaffolding techniques [22]. Similarly, the application of stem cells in engineered vascular grafts has been shown to enhance vascularization and improve graft longevity [23]. However, the choice of technique often hinges on the specific clinical scenario; for instance, injectable hydrogels have gained traction for cartilage repair due to their minimally invasive application and ability to conform to defect geometries [24]. Despite these advancements, challenges remain, such as the need for improved mechanical properties in engineered tissues to withstand physiological loads [25]. Overall, the effectiveness of tissue engineering techniques is contingent upon a careful consideration of the biological and mechanical demands of the target tissue.
Discussion on Indications and Contraindications: The application of tissue engineering techniques is not universally appropriate; understanding the indications and contraindications is crucial for optimizing patient outcomes. Indications for tissue engineering include acute injuries, chronic degenerative conditions, and cases where traditional surgical interventions have failed. For instance, engineered scaffolds have shown efficacy in repairing osteochondral defects, offering a viable alternative to joint replacement in select patients [26]. Conversely, contraindications may include active infections, significant comorbidities, or conditions that impair healing, such as diabetes or vascular diseases [27]. Additionally, the presence of senescent cells can negatively impact tissue regeneration, highlighting the need for patient selection and preoperative assessment [28]. As the field continues to evolve, ongoing research will be essential to refine these indications and contraindications, ensuring that tissue engineering techniques are applied in the most beneficial contexts.
Efficacy Evaluation of Tissue Engineering Repair Techniques
Establishment of Clinical Efficacy Indicators: The establishment of clinical efficacy indicators is crucial in evaluating the success of tissue engineering repair techniques. These indicators typically encompass a range of parameters, including functional outcomes, radiographic evidence of healing, and patient-reported outcomes. Functional outcomes refer to the restoration of normal function in the affected area, which can be quantitatively assessed through various scoring systems relevant to the specific tissue type being repaired. For instance, in periodontal tissue regeneration, indicators such as probing depth reduction and clinical attachment level gain are commonly utilized to assess the effectiveness of the intervention [29]. Furthermore, radiographic assessments, such as imaging techniques that visualize tissue integration and bone regeneration, provide objective data that complement clinical evaluations [30]. It is also essential to consider patient-reported outcomes, which reflect the patients’ perceptions of their recovery and overall quality of life following the procedure. This multidimensional approach to establishing efficacy indicators ensures a comprehensive evaluation of the therapeutic interventions in tissue engineering.
Follow-Up Results and Improvement in Patient Quality of Life: Follow-up studies play a pivotal role in assessing the long-term efficacy of tissue engineering repair techniques and their impact on patients’ quality of life. Research shows that patients who undergo tissue engineering procedures often report significant improvements in their quality of life, attributed to enhanced functional capabilities and reduced pain levels [31]. For example, in cases of temporomandibular joint disorders, patients have demonstrated improved chewing ability and decreased discomfort following tissue engineering interventions aimed at repairing disc perforations [32]. Longitudinal studies highlight that these improvements are not only immediate but can also persist over extended periods, underscoring the sustainability of the benefits derived from such innovative treatments [33]. Furthermore, the use of validated quality of life assessment tools, such as the Short Form Health Survey (SF-36), allows for standardized comparisons across different studies, enhancing the reliability of the findings regarding patient outcomes [34]. Overall, the evidence suggests that successful tissue engineering repair techniques can lead to substantial enhancements in patients’ daily lives and overall well-being.
Complications and Safety Analysis: An integral aspect of evaluating the efficacy of tissue engineering repair techniques is the analysis of complications and overall safety. While these innovative approaches hold great promise, they are not without risks. Complications can range from minor issues, such as localized infections or inflammation, to more severe outcomes, such as graft failure or adverse reactions to biomaterials used in the repair process [35]. A systematic review of complications associated with various tissue engineering applications indicates that the incidence of adverse events varies significantly based on the type of tissue being repaired and the specific techniques employed [36]. For instance, in reconstructive procedures involving skin or soft tissue, the complication rates are generally lower compared to those observed in more complex repairs, such as vascular or osseous reconstructions [37]. Safety analyses are essential not only for understanding the risk profile associated with these interventions but also for guiding clinical practice and improving patient outcomes. Continuous monitoring and reporting of complications in clinical settings can help refine techniques and materials used in tissue engineering, ultimately enhancing patient safety and treatment efficacy [38].
Mechanistic Exploration: Biological Basis of Tissue Engineering Repair Techniques
Biological Mechanisms of Bone Regeneration: Bone regeneration is a complex biological process that involves the coordinated actions of various cellular and molecular components. The primary mechanisms include osteogenesis, angiogenesis, and the remodeling of the extracellular matrix (ECM). Osteogenesis is driven by osteoblasts, which synthesize new bone matrix, while osteoclasts are responsible for bone resorption, ensuring a balance that is crucial for proper bone healing. Recent studies have highlighted the role of biomaterials in enhancing these processes, particularly through the use of polymeric scaffolds that mimic the natural bone structure and promote cell attachment and proliferation [39]. Additionally, the presence of growth factors, such as bone morphogenetic proteins (BMPs), has been shown to significantly enhance osteogenic differentiation and promote angiogenesis, which is essential for providing nutrients and oxygen to the regenerating tissue [40]. Furthermore, advancements in nanomaterials have opened new avenues for improving bone regeneration by enhancing the bioactivity of scaffolds and facilitating cellular interactions [41]. The interplay between these biological mechanisms and the scaffolding materials used in tissue engineering is vital for achieving successful bone regeneration.
Research on Cell-Matrix Interactions: Cell-matrix interactions play a pivotal role in tissue engineering, influencing cell behavior, differentiation, and tissue formation. The extracellular matrix (ECM) provides not only structural support but also biochemical cues that regulate cellular functions. Recent research has focused on understanding how cells respond to the mechanical and biochemical properties of the ECM. For instance, studies have demonstrated that the stiffness of the matrix can affect stem cell differentiation, with stiffer matrices promoting osteogenic differentiation and softer matrices favoring adipogenic pathways [42]. Additionally, the incorporation of bioactive molecules within scaffolds can enhance cell adhesion and promote specific cellular responses, thereby facilitating tissue regeneration [43]. The dynamic interactions between cells and the ECM are also essential for maintaining tissue homeostasis and orchestrating responses to injury. By elucidating these interactions, researchers can design more effective biomaterials that promote optimal cell behavior and enhance tissue repair [44].
Regulation of Immune and Inflammatory Responses: The immune response plays a critical role in the success of tissue engineering strategies, as inflammation is a natural response to injury that can either facilitate or hinder healing. Understanding the regulation of immune and inflammatory responses is essential for developing effective tissue engineering approaches. Recent studies have highlighted the importance of the local microenvironment in modulating immune responses. For example, the presence of certain cytokines and growth factors can either promote or suppress inflammation, thereby influencing the overall healing process [45]. Moreover, the design of biomaterials that can actively modulate the immune response has gained attention, with some materials demonstrating the ability to promote a pro-regenerative immune environment while minimizing adverse inflammatory reactions [46]. The interplay between immune cells and the ECM also plays a significant role in tissue repair, as immune cells can influence fibroblast activity and ECM remodeling [47]. Thus, a comprehensive understanding of these regulatory mechanisms is crucial for optimizing tissue engineering strategies and enhancing the regenerative potential of engineered tissues.
Future Directions and Challenges
Prospects for the Application of New Materials and Technologies: The integration of new materials and technologies in healthcare is rapidly evolving, offering significant potential for improving patient outcomes. Recent advancements in nanotechnology, particularly in the synthesis of nanogels, have shown promise in drug delivery systems, enhancing the bioavailability of therapeutic agents while minimizing side effects [48]. Similarly, the development of advanced materials based on nanosized hydroxyapatite has implications for bone regeneration and dental applications, showcasing how innovative materials can enhance healing processes [49]. Furthermore, the exploration of dielectric elastomers as artificial muscles presents exciting opportunities for creating more responsive and adaptable medical devices [50]. However, these advancements come with challenges, including the need for rigorous safety evaluations and regulatory approvals before widespread clinical application. As we look toward the future, the collaboration between material scientists and medical professionals will be crucial in overcoming these hurdles and ensuring that new technologies are effectively translated into practice.
Exploration of Personalized Treatment: The shift towards personalized medicine represents a transformative approach in healthcare, emphasizing the need to tailor treatments to individual patient characteristics. Recent studies have highlighted the importance of individualizing therapeutic strategies, particularly in chronic diseases such as diabetes and cancer [51,52]. For instance, personalized cancer therapies, including T-cell therapies, have demonstrated improved efficacy by aligning treatment protocols with specific tumor profiles [53]. Additionally, tailoring treatment strategies for conditions like Crohn’s disease has shown promise in enhancing patient adherence and outcomes [54]. However, the implementation of personalized medicine faces challenges, including the need for comprehensive genomic data and the integration of sophisticated bioinformatics tools to analyze patient-specific information. Moving forward, a multidisciplinary approach that incorporates genetic, environmental, and lifestyle factors will be essential in refining personalized treatment paradigms.
The Necessity of Multidisciplinary Collaboration: Multidisciplinary collaboration is increasingly recognized as a cornerstone of effective healthcare delivery, particularly in complex cases requiring diverse expertise. Research has shown that collaborative practices in healthcare settings can significantly enhance patient care quality and outcomes [55]. For example, integrated management teams in oncology have been shown to improve treatment coordination and patient satisfaction [56]. Additionally, the significance of cooperation among various healthcare professionals is vital in addressing the multifaceted needs of patients, especially in geriatric care settings [57]. However, fostering effective collaboration poses challenges, including communication barriers and differing professional cultures. To address these issues, training programs focused on teamwork and communication skills are essential. As we advance, promoting a culture of collaboration within healthcare organizations will be crucial in optimizing patient care and addressing the complexities of modern medical challenges. In conclusion, the application of tissue engineering repair techniques in the treatment of early to mid-stage femoral head necrosis has demonstrated promising efficacy and safety profiles. The integration of biomaterials, stem cells, and growth factors has paved the way for innovative therapeutic approaches that not only aim to restore the structural integrity of the femoral head but also enhance regenerative capacity. Current evidence indicates that these techniques can significantly improve patient outcomes, reducing the need for more invasive surgical interventions and promoting faster recovery times. However, while the preliminary results are encouraging, it is imperative to recognize the necessity for further research to substantiate these findings.
There remains a need for large-scale, multicenter clinical trials to validate the long-term effectiveness and safety of tissue engineering interventions. Moreover, standardization of protocols and materials used in tissue engineering is crucial to facilitate comparability between studies and to establish best practices within clinical settings. Balancing differing viewpoints and findings in the literature is essential for advancing the field. Some studies highlight the potential of tissue engineering to revolutionize treatment approaches, while others raise concerns about the variability in outcomes due to differences in methodologies and patient populations. It is essential that future research focuses on elucidating the mechanisms underlying the success of these techniques, as well as identifying patient-specific factors that may influence treatment outcomes. In terms of clinical practice, it is recommended that healthcare providers remain informed about the evolving landscape of tissue engineering technologies and consider their application on a case-by-case basis. Emphasizing a multidisciplinary approach, incorporating insights from orthopedic surgeons, bioengineers, and rehabilitation specialists, will enhance the comprehensive management of femoral head necrosis. As we look ahead, the future of tissue engineering in this domain appears bright, but continued investment in research and collaboration among stakeholders will be vital to unlock the full potential of these innovative therapies. By addressing the prevailing challenges and fostering a culture of inquiry, we can ensure that tissue engineering repair techniques are effectively integrated into routine clinical practice, ultimately improving the quality of life for patients suffering from femoral head necrosis.
National Key Research and Development Program: 2024YFA110860