Key Takeaways & Executive Findings
- •• The mZIF-8/PLA membrane, fabricated via electrospinning and biomimetic mineralization, exhibits enhanced hydrophilicity and cell compatibility, promoting osteogenesis and angiogenesis in BMSCs. • The membrane induces M2 macrophage polarization, modulating the local immune microenvironment to support bone regeneration. • In vivo, the membrane bridges critical-sized bone defects within 4 weeks and achieves near-complete repair by 12 weeks, with improved bone strength and vascularization. • This dual-functional membrane offers a promising strategy for guided bone regeneration, addressing limitations of current barrier membranes in osteoinduction and immunomodulation.
Abstract
Background Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. Methods The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. Results The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. Conclusions The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.
1. Introduction
Bone defects commonly arise from various causes such as trauma, infections, and tumors [1]. A significant challenge in the healing of large bone defects is the rapid growth of connective tissue that impedes new bone formation. Guided bone regeneration (GBR) technology has been developed to address this issue and is widely used in orthopedics and dentistry [2–3]. The success of GBR treatment hinges on the properties of the barrier membrane, which acts as a physical barrier separating soft tissue from the bone defect area to prevent interference by fibrous connective tissue. By allowing osteoblasts to proliferate within the bone defect area, the GBR membrane facilitates new bone formation. Therefore, the barrier membrane plays a crucial role in promoting the proliferation and regeneration of bone tissue [4].
Bone-guided membrane materials used in preclinical applications can be categorized into biodegradable and nonbiodegradable types [5, 6]. The nonbiodegradable bone guide membrane typically consist of materials such as polytetrafluoroethylene [7] and titanium [8, 9]. While these nondegradable membrane offer stable material properties and high mechanical strength, they often require a second surgical procedure of removal, potentially leading to complications like mucosal dehiscence, exposure, and postoperative infection [10]. In order to minimize patient discomfort, costs, tissue invasion, and the risk of new bone tissue loss, biodegradable materials are preferred over nonbiodegradable ones for clinical applications. Therefore, studies focused on absorbable membranes based on polymers (both natural and artificial), including collagen (for example, Bio-Gide™ from Wolhusen, Switzerland) [11], polyglycolic acid [12], polylactic acid (PLA) [13], and polycaprolacton [14]. PLA is a particularly suitable for electrospun membrane preparation due to its biocompatibility and non-bioaccumulative nature in vital organs [15]. However, the lack of osteoinductive properties in PLA presents a significant challenge when utilizing it in bone tissue engineering.
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Bingqian Wang, Xinfang Xie, Wenbin Jiang, Yichen Zhan, Yifan Zhang, Yaqi Guo, Zhenxing Wang, Nengqiang Guo, Ke Guo, Jiaming Sun (2026). Osteoinductive micro-nano guided bone regeneration membrane for in situ bone defect repair. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03745-w
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Frequently Asked Questions
What is the mZIF-8/PLA membrane?
The mZIF-8/PLA membrane is a guided bone regeneration membrane fabricated by electrospinning polylactic acid (PLA) with zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, followed by biomimetic mineralization in simulated body fluid. It combines osteoconductive and immunomodulatory properties for enhanced bone repair.
How does the mZIF-8/PLA membrane promote bone regeneration?
The membrane enhances hydrophilicity and cell compatibility, promotes upregulation of osteogenic and angiogenic factors in bone marrow mesenchymal stem cells (BMSCs), and induces macrophage polarization toward the M2 phenotype, creating a favorable immune microenvironment for bone regeneration.
What are the advantages of the mZIF-8/PLA membrane over traditional GBR membranes?
Unlike nondegradable membranes that require removal surgery, the mZIF-8/PLA membrane is biodegradable. It also addresses the lack of osteoinductive properties in pure PLA by incorporating ZIF-8, and its immunomodulatory effects help reduce inflammation and promote tissue integration.
What were the in vivo results of the mZIF-8/PLA membrane?
In a rat model, the membrane successfully bridged critical-sized bone defects within 4 weeks and achieved near-complete repair by 12 weeks, with significantly improved bone strength and vascularization compared to controls.
What is the significance of this study for clinical applications?
The study provides a novel dual-functional membrane that not only acts as a physical barrier but also actively stimulates bone formation and modulates the immune response, offering a promising strategy for improving outcomes in bone defect repair and potentially reducing the need for secondary surgeries.
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