Kewen Zhang, Yanwen Zhou, Daixu Wei, Airong Qian, Xiao Lin

doi:https://doi.org/10.12336/bmt.25.00072

Addressing bone defects caused by degenerative diseases, trauma, and cancer through bone tissue engineering remains a significant global health challenge. The osteoinductive properties of bone morphogenetic protein-2 (BMP2) have become a key therapeutic strategy in bone regeneration. However, the development of biodegradable composites that ensure biocompatibility, stability, efficient BMP2 loading, and controlled release remains unresolved. In this study, we designed PBVHx/soy lecithin (SL)/BMP2 controlled-release microspheres (sB2PM) based on the biodegradable material poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx), incorporating SL to enable sustained BMP2 delivery and enhance capture. sB2PM microspheres exhibited uniform size (approximately 5 μm) and high BMP2 encapsulation efficiency (80.29%) compared to pure PBVHx-based microspheres (pPM). Due to PBVHx’s biodegradability, BMP2 release was primarily degradation-driven, resulting in a controlled biphasic release profile. sB2PM achieved 62.79% cumulative BMP2 release over four weeks and continued to release BMP2 sustainably thereafter. Co-culturing sB2PM microspheres with human bone marrow-derived mesenchymal stem cells (hBMSCs) in a Transwell system showed enhanced cell proliferation, biocompatibility, and collagen secretion. Compared with pPM and B2PM, sB2PM significantly promoted osteogenic differentiation, increased alkaline phosphatase (ALP) activity, and upregulated osteogenic gene expression in hBMSCs, outperforming commercial hydroxyapatite microspheres. In a mouse hindlimb unloading osteoporosis model, micro computed tomography and histological evaluations confirmed that injectable sB2PM microspheres significantly enhanced bone regeneration, collagen secretion, and ALP and runt-related transcription factor 2 protein expression. This study highlights the potential of sB2PM microspheres with controlled BMP2 release for future bone regeneration therapies.

Siufui Hendrawan, Olivia Marcelina, Astheria Eryani, Erwin Siahaan, Hans U. Baer

doi:https://doi.org/10.12336/bmt.25.00041

Present standard treatment for incisional hernia (IH) focuses on wound closure by providing mechanical reinforcement to the affected tissue, generally through the implantation of synthetic polypropylene (PP) mesh. However, PP mesh primarily functions to hold organs in place and does not actively stimulate intrinsic tissue regeneration. Meanwhile, in the aging population and in individuals with pre-existing complications, impaired wound healing and reduced elasticity increase the risk of hernia recurrence. In this study, we developed a three-dimensional cellularized implant with secretome (Sec) supplementation, aiming to promote tissue regeneration and the formation of a more mechanically robust scar in IH repair. The cellularized matrix (Cell/Matrix) was produced by seeding fibroblasts onto a three-dimensional collagen-coated poly-L-lactic acid matrix. Supplementation with Sec derived from human umbilical cord mesenchymal stem cells was performed to produce the Cell/Matrix+Sec implant. Implantation was performed in the sublay position (between muscle and peritoneal membrane), beneath an incisional cut at the midline abdomen of Wistar rats to mimic IH repair. Rats with no implant (Sham) served as the control group, while others received PP mesh (Mesh), an acellularized matrix (Matrix), Cell/Matrix, and Cell/Matrix+Sec implants. At 2 months post-implantation, abdominal tissue samples extracted from the Cell/Matrix+Sec implant group exhibited the greatest biomechanical strength, accompanied by a higher collagen type I/III ratio, neovascularization count, α-smooth muscle actin-positive vessels, and formation of neuron bundles. Meanwhile, Sham and Mesh groups displayed the lowest values in all parameters, respectively. Despite having lower mechanical strength compared with PP mesh, implantation of the cellularized matrix resulted in better muscle tissue integrity and maturation. Hence, these findings highlight the potential of Cell/Matrix+Sec as a novel adjuvant implant to complement the present standard approach to hernia repair, which lacks regenerative capacities.

Akram Hoshyari, Reza Ahmadi, Mojgan Heydari, Mozhgan Bagheri, Nader Nezafati

doi:https://doi.org/10.12336/bmt.25.00020

Gelatin nanoparticles (GNPs) have been designed and characterized to enable the controlled release of tramadol, offering potential for improved drug delivery and sustained therapeutic effects. In this study, biocompatible GNPs for controlled release of water-soluble drug tramadol were prepared through the water-in-oil emulsion method using Yucca schidigera extract as an eco-friendly, natural green co-surfactant. The presence of an aldimine functional group in the structure of GNPs was confirmed using Fourier-transform infrared spectroscopy, indicating cross-linking of gelatin by glutaraldehyde. In addition, the NPs exhibited a uniform, spherical structure without cracks, and the average particle size increased from 70 to 350 nm as the percentage of the cross-linker agent decreased from 25% to 8% v/v. The ninhydrin test was used to study the degree of cross-linking, and the results showed that 8% and 25% v/v of glutaraldehyde were able to cross-link the gelatin structure. The swelling index of GNPs cross-linked with 25% v/v glutaraldehyde (798%) was lower than with 8% v/v glutaraldehyde (1,030%). The GNP-to-tramadol ratios and glutaraldehyde concentration were optimized for tramadol release, and the results showed that cross-linked gelatin with 25% v/v glutaraldehyde and a GNP-to-tramadol ratio of 1:5 exhibited the most optimal characteristics for controlled drug delivery. Drug release kinetics analysis revealed that the release mechanism is concentration-dependent and best described by a first-order model, indicating a non-Fickian, diffusion-controlled process. Moreover, tramadol released from GNPs showed controlled behavior compared to the commercial tablet. Furthermore, the use of Yucca extract with proven emulsifying and stabilizing properties enhanced NP formation, highlighting its potential as a sustainable alternative to synthetic surfactants. The results confirmed that the designed drug delivery system could be a potential candidate for the delivery and controlled release of drugs such as tramadol compared to available conventional tablets.

Rawia Khalil, Mohamed F. AbdelHameed, Shaymaa A. Ismail, Amira A. Hassan, Marwa E. Shabana, Wenli Zhang, Eman S. Shalaby

doi:https://doi.org/10.12336/bmt.25.00039

Wound management remains a global health concern due to its fatal complications, and cetrimide (CET) is an antimicrobial quaternary ammonium chemical used in wound healing. This study aimed to develop and assess the therapeutic potential of a CET-loaded nanoemulsion for treating methicillin-resistant Staphylococcus aureus-infected wounds. A high-speed homogenization method was used for preparing nanoemulsions containing CET, sesame oil, and linalool. Entrapment efficiency, droplet size, and zeta potential were evaluated to identify the optimal formulations. Further characterization included in vitro release studies, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and transmission electron microscopy. The selected formulations were subsequently evaluated for their in vivo wound healing efficacy in a full-thickness wound model. The formulated nanoemulsion demonstrated high entrapment efficiency (92.71– 98.57%), with droplet sizes of 150–399 nm and zeta potential of +10–+27.9 mV, suggesting favorable physical stability. The in vitro drug release followed a biphasic pattern. DSC peaks of the drug were diffused in the formulation, suggesting its presence in the amorphous form. FTIR study showed no new peaks, suggesting no chemical interaction between the drug and the formulation components. In vivo evaluation of wound healing efficacy revealed a marked reduction in wound size following treatment with selected CET-loaded nanoemulsions. In addition, a significant decrease in tumor necrosis factor-alpha levels, alongside increased expression of B-cell lymphoma 2 and collagen type I, was observed in treated rats. Histological analysis further supported these findings, revealing near-normal tissue architecture. Collectively, these results indicate that CET-loaded nanoemulsions represent a promising approach for enhancing topical wound healing outcomes.

Rittin Abraham Kurien, Gokul Kannan, Kasitpong Thanawut, Supakij Suttiruengwong, Pornsak Sriamornsak

doi:https://doi.org/10.12336/bmt.25.00043

Artificial intelligence (AI) and 3D printing are transforming pharmaceutical manufacturing by enabling the production of personalized medications. AI supports real-time decision-making in diagnostics and robotics, although its application in pharmaceutical research remains at an early stage. 3D printing, particularly additive manufacturing, provides precise control over drug formulation, allowing the design of patient-specific dosage forms with tailored release profiles. Machine learning and deep neural networks are used to predict formulation parameters, optimize processing conditions, and support the design of innovative drug delivery geometries. Technological platforms such as cloud computing and blockchain enhance data security, transparency, and scalability. Printable materials—including thermoplastic polymers, hydrogels, and bioinks—demonstrate utility in AI-assisted manufacturing systems. The integration of AI, smart materials, and 3D printing advances intelligent drug production technologies aligned with Industry 4.0 principles. Key considerations include regulatory compliance, data reliability, ethical implications, and pathways for clinical translation. Clinical medicine is rapidly advancing through the adoption of 3D printing and AI, enabling personalized prosthetics, accurate surgical planning, and bioprinted tissues. AI-driven segmentation and optimization enhance the accuracy and efficiency of 3D-printed anatomical models for pre-operative preparations and medical training. Cardiology, oncology, and orthopedics are increasingly adopting these technologies to improve patient outcomes and clinical workflows. Future directions include broader adoption across specialties, bioprinting for regenerative health care, and AI-optimized systems for targeted drug delivery. This review addresses the current challenges and limitations of AI and 3D-printed medicines, pharmaceutical manufacturing, case studies, ethical considerations, and future perspectives.