bims-biprem 2024-11-10 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–11–10
thirteen papers selected by
Seerat Maqsood, University of Teramo

Simulating the in vivo tumor microenvironment-advances in building a vascularized model of hepatocellular carcinoma through 3D bioprinting.
Highly porous sildenafil loaded polylactic acid/polyvinylpyrrolidone based 3D printed scaffold containing forsterite nanoparticles for craniofacial reconstruction.
Leveraging solid solubility and miscibility of etoricoxib in Soluplus® towards manufacturing of 3D printed etoricoxib tablets by additive manufacturing.
Magnetic 3D bioprinting of skeletal muscle spheroid for a spheroid-based screening assay.
3D printed cell-free bilayer porous scaffold based on alginate with biomimetic microenvironment for osteochondral defect repair.
3D Bioprinting a Novel Skin Co-Culture Model Using Human Keratinocytes and Fibroblasts.
3D-Printed Polymeric Biomaterials for Health Applications.
FRESH 3D printing of zoledronic acid-loaded chitosan/alginate/hydroxyapatite composite thermosensitive hydrogel for promoting bone regeneration.
Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery.
3D printed gelatin/PTMC core/shell scaffolds with NIR laser-tuned drug/biomolecule release for cancer therapy and uterine regeneration.
4D printing of smart scaffolds for bone regeneration: a systematic review.
Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.
Incorporating Hydrogel (with Low Polymeric Content) into 3D-Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects.

Hepatobiliary Surg Nutr. 2024 Oct 01. 13(5): 882-884

Simulating the in vivo tumor microenvironment-advances in building a vascularized model of hepatocellular carcinoma through 3D bioprinting.

Liwei Du, Huayu Yang.



Keywords:  Three-dimensional bioprinting (3D bioprinting); hepatocellular carcinoma (HCC); individualized treatment; vascularized model

DOI:  https://doi.org/10.21037/hbsn-24-154
Int J Biol Macromol. 2024 Nov 03. pii: S0141-8130(24)08064-4. [Epub ahead of print]282(Pt 4): 137255

Highly porous sildenafil loaded polylactic acid/polyvinylpyrrolidone based 3D printed scaffold containing forsterite nanoparticles for craniofacial reconstruction.

Nafise Kazemi, S A Hassanzadeh-Tabrizi, Narjes Koupaei, Hamed Ghomi, Elahe Masaeli.

  Tissue engineering has emerged as a promising substitute for traditional tissue repair methods. Nowadays, advancements in 3D printing technology have enabled the fabrication of customized scaffolds to support tissue regeneration. In the present study, a polylactic acid-polyvinylpyrrolidone 3D-printed scaffold containing 10 % forsterite was fabricated. Subsequently, lyophilized fucoidan microstructures loaded with sildenafil were filled the channels of this 3D-printed scaffold. The fabricated scaffold loaded with sildenafil was thoroughly characterized, revealing that 97.46 % of the loaded sildenafil was released in a sustained manner over 28 days. Furthermore, the biocompatibility of MG63 was evaluated through cell viability and adhesion tests. The findings indicated a direct and favorable influence on cell behavior. Based on the chicken chorioallantoic membrane assay, the fabricated scaffold significantly increases angiogenesis due to the sustained release of sildenafil. Moreover, in-vivo studies conducted on a rat model demonstrated that the 3D-printed scaffold was able to stimulate and accelerate the repair of calvarial defects within 8 weeks, and the amount of new bone tissue formation was significantly higher than that of other experimental groups. Based on the comprehensive in-vitro and in-vivo assessments, the scaffold with a macro- and microporous structure combined with the ability to release sildenafil is suggested as a potential candidate for repairing bone tissue, especially in the context of skull defects.

Keywords:  3D printing; Forsterite; Fucoidan, sildenafil; Tissue engineering scaffold

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137255
Int J Pharm. 2024 Oct 26. pii: S0378-5173(24)01115-3. [Epub ahead of print] 124881

Leveraging solid solubility and miscibility of etoricoxib in Soluplus® towards manufacturing of 3D printed etoricoxib tablets by additive manufacturing.

Makka Krupali Ashokbhai, Shubham Ghatole, Ujjwal Gupta, Lohare Rahul Sanjay, Subhadeep Roy, Velayutham Ravichandiran, Santanu Kaity.

  This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form. This study's novelty lies in combining HME and 3D printing, aiming to improve drug incorporation, stability, and effectiveness in the final formulation. Comprehensive characterization techniques, including hot stage microscopy (HSM), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), florescence microscopy, optical microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), solubility studies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and aqueous solubility study were utilized to elucidate the physicochemical properties, thermal stability, and structural integrity for the extruded filaments (the printing ink), and 3D printed tablets made thereof. Furthermore, the in vitro drug release profile of the 3D printed tablet was systematically evaluated, revealing a controlled drug release pattern from the finished dosage form. The systematic investigation reported herein, starting from theoretical miscibility to the printing ink development through HME, detailed characterization of the extruded filaments, and further solid oral formulation development by additive manufacturing can be utilized as a platform technology or a pathway for the development of personalized medicine with drugs having similar physicochemical properties.

Keywords:  3D printed tablet; Additive manufacturing; Drug-polymer miscibility; Etoricoxib; Soluplus

DOI:  https://doi.org/10.1016/j.ijpharm.2024.124881
SLAS Discov. 2024 Oct 26. pii: S2472-5552(24)00052-2. [Epub ahead of print] 100190

Magnetic 3D bioprinting of skeletal muscle spheroid for a spheroid-based screening assay.

Chayanit Chaweewannakorn, Khin The Nu Aye, Joao N Ferreira.

  Over the past decade, there has been a rapid development in the use of magnetic three dimensional (3D) based cell culture systems. Concerning the skeletal muscle, 3D culture systems can provide biological insights for translational clinical research in the fields of muscle physiology and metabolism. These systems can enhance the cell culture environment by improving spatially-oriented cellular assemblies and morphological features closely mimicking the in vivo tissues/organs, since they promote strong interactions between cells and the extracellular matrix (ECM). However, the time-consuming and complex nature of 3D traditional culture techniques pose a challenge to the widespread adoption of 3D systems. Herein, a bench protocol is presented for creating an innovative, promptly assembled and user-friendly culture platform for the magnetic 3D bioprinting of skeletal muscle spheroids. Our protocol findings revealed consistent morphological outcomes and the functional development of skeletal muscle tissue, as evidenced by the expression of muscle-specific contractile proteins and myotubes and the responsiveness to stimulation with cholinergic neurotransmitters. This proof-of-concept protocol confirmed the future potential for further validation and application of spheroid-based assays in human skeletal muscle research.

Keywords:  3D cell culture; bioprinting; magnetic; nanoparticles; skeletal muscle

DOI:  https://doi.org/10.1016/j.slasd.2024.100190
Biomater Adv. 2024 Oct 31. pii: S2772-9508(24)00335-2. [Epub ahead of print]167 214092

3D printed cell-free bilayer porous scaffold based on alginate with biomimetic microenvironment for osteochondral defect repair.

Hui Wang, Jiaxin Zhang, Haotian Bai, Chenyu Wang, Zuhao Li, Zhonghan Wang, Qingping Liu, Zhenguo Wang, Xianggang Wang, Xiujie Zhu, Jiaqi Liu, Jincheng Wang, Xin Zhao, Luquan Ren, He Liu.

  Despite significant progress in repairing osteochondral injuries using 3D printing technology, most cartilage layer scaffolds are made of degradable materials, making it difficult to simultaneously provide extracellular matrix functionality while replicating the mechanical properties of natural cartilage layers. Additionally, their degradation rate is challenging to align with cartilage regeneration. Furthermore, double-layer scaffolds commonly used for repairing osteochondral often exhibit inadequate bonding between the cartilage layer scaffolds and bone layer scaffolds. To solve these problems, we presented a bilayer scaffold composed of a 3D printed non-degradable thermoplastic polyurethane (TPU) scaffold filled with hydrogel (Gel) made of gelatin and sodium alginate as the cartilage layer (noted as TPU/Gel), meanwhile, a 3D printed polylactic acid (PLA) scaffold containing 10 % hydroxyapatite (HA) as the bone layer (noted as PLA/HA). At the junction of the bone layer and cartilage layer, TPU tightly bonded with the bone layer scaffold under high temperatures. The hydrogel filling within the TPU layer of cartilage served not only to lubricate the joint surface but also aided in creating a 3D microenvironment. The non-degradable nature of TPU allowed the cartilage layer scaffold to seamlessly integrate with the surrounding regenerated cartilage, achieving permanent replacement and providing shock absorption and weight-bearing effects. This effectively addressed the mechanical challenges associated with cartilage regeneration and resolved the inconsistency between cartilage regeneration and material degradation rates.

Keywords:  3D printing; And subchondral bone injuries; Bilayer scaffold; Cartilage; Osteochondral

DOI:  https://doi.org/10.1016/j.bioadv.2024.214092
J Biomed Mater Res A. 2024 Nov 02.

3D Bioprinting a Novel Skin Co-Culture Model Using Human Keratinocytes and Fibroblasts.

Thiago A M Andrade, Victor Allisson da Silva, Kali Scheck, Tania Garay, Ruchi Sharma, Stephanie M Willerth.

  3D bioprinting can generate the organized structures found in human skin for a variety of biological, medical, and pharmaceutical applications. Challenges in bioprinting skin include printing different types of cells in the same construct while maintaining their viability, which depends on the type of bioprinter and bioinks used. This study evaluated a novel 3D bioprinted skin model containing human keratinocytes (HEKa) and human dermal fibroblasts (HDF) in co-culture (CC) using a high-viscosity fibrin-based bioink produced using the BioX extrusion-based bioprinter. The constructs containing HEKa or HDF cells alone (control groups) and in CC were evaluated at 1, 10, and 20 days after bioprinting for viability, immunocytochemistry for specific markers (K5 and K10 for keratinocytes; vimentin and fibroblast specific protein [FSP] for fibroblasts). The storage, loss modulus, and viscosity properties of the constructs were also assessed to compare the effects of keratinocytes and fibroblasts individually and combined, providing important insights when bioprinting skin. Our findings revealed significantly higher cell viability in the CC group compared to individual keratinocyte and fibroblast groups, suggesting the combined cell presence enhanced survival rates. Additionally, proliferation rates of both cell types remained consistent over time, indicating non-competitive growth within the construct. Interestingly, keratinocytes exhibited a greater impact on the viscoelastic properties of the construct compared to fibroblasts, likely due to their larger size and arrangement. These insights contribute to optimizing bioprinting strategies for skin tissue engineering and emphasize the important role of different cell types in 3D skin models.

Keywords:  3D bioprinting; cell viability; co‐culture; human skin model; rheology; tissue engineering

DOI:  https://doi.org/10.1002/jbm.a.37831
Adv Healthc Mater. 2024 Nov 05. e2402571

3D-Printed Polymeric Biomaterials for Health Applications.

Yuxiang Zhu, Shenghan Guo, Dharneedar Ravichandran, Arunachalam Ramanathan, M Taylor Sobczak, Alaina F Sacco, Dhanush Patil, Sri Vaishnavi Thummalapalli, Tiffany V Pulido, Jessica N Lancaster, Johnny Yi, Jeffrey L Cornella, David G Lott, Xiangfan Chen, Xuan Mei, Yu Shrike Zhang, Linbing Wang, Xianqiao Wang, Yiping Zhao, Mohammad K Hassan, Lindsay B Chambers, Taylor G Theobald, Sui Yang, Liang Liang, Kenan Song.

  3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health-related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D-printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state-of-the-art in 3D-printed functional polymeric health-related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D-printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self-powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.

Keywords:  advanced manufacturing; biomedical; healthcare; pharmaceutical; regenerative medicine

DOI:  https://doi.org/10.1002/adhm.202402571
Int J Pharm. 2024 Nov 03. pii: S0378-5173(24)01132-3. [Epub ahead of print]667(Pt A): 124898

FRESH 3D printing of zoledronic acid-loaded chitosan/alginate/hydroxyapatite composite thermosensitive hydrogel for promoting bone regeneration.

Reem Khaled Wassif, Baher A Daihom, Mohammed Maniruzzaman.

  The aim of this study was to develop a composite thermosensitive hydrogel for bone regeneration applications. This hydrogel consisted of chitosan, alginate and hydroxyapatite, and was loaded with zoledronic acid as a model drug. The feasibility of three-dimensional (3D) printing of the thermosensitive hydrogel using the extrusion based technique was investigated. The 3D printing technique called Freeform Reversible Embedded Suspended Hydrogel (FRESH) printing was employed for this purpose. To characterize the composite hydrogels, several tests were conducted. The gelation time, rheological properties, and in vitro drug release were analyzed. Additionally, the cell viability test on human osteosarcoma MG-63 cells for the composite hydrogel was assessed using an MTT assay. The results of the study showed that the zoledronic acid-loaded composite thermosensitive hydrogel was successfully printed using the FRESH 3D printing technique which was not possible otherwise i.e., by using traditional 3D printing techniques. Further examination of the printed constructs using a Scanning Electron Microscope revealed the presence of porous and layered structures. The gelation times of the composite thermosensitive hydrogel was determined to be 10 and 20 min, respectively for scaffolds with and without HA, indicating the successful formation of the gel within a reasonable time to the FRESH technique. The flow behavior of the hydrogel was found to be pseudoplastic, following a non-Newtonian flow pattern with Farrow's constant (N) values of 1.708 and 1.853 for scaffolds with and without hydroxyapatite, respectively. In terms of drug release, scaffolds prepared with and without hydroxyapatite reached nearly 100% of zoledronic acid release in 360 h and 48 h, respectively. The cell viability test on human osteosarcoma MG-63 cells using MTT assay has shown increased cell viability % in the case of composite hydrogel, indicating biocompatibility of the scaffold. Overall, this study successfully developed a composite thermosensitive hydrogel loaded with zoledronic acid for bone regeneration applications and was 3D printed using the FRESH 3D printing technique. The results of this study provide valuable insights into the potential use of this composite hydrogel for future biomedical applications.

Keywords:  3D printing; Bone regeneration; FRESH Printing; Hydroxyapatite; Thermosensitive hydrogel; Zoledronic acid

DOI:  https://doi.org/10.1016/j.ijpharm.2024.124898
Colloids Surf B Biointerfaces. 2024 Oct 23. pii: S0927-7765(24)00596-4. [Epub ahead of print]245 114337

Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery.

Yiqian Zhu, Xuezhe Liu, Keyi Zhang, Mohamed El-Newehy, Meera Moydeen Abdulhameed, Xiumei Mo, Lei Cao, Yongfei Wang.

  Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

Keywords:  3D-printing; Electrospinning; Skull base reconstruction; Tissue engineering; Transnasal

DOI:  https://doi.org/10.1016/j.colsurfb.2024.114337
Int J Biol Macromol. 2024 Nov 03. pii: S0141-8130(24)08002-4. [Epub ahead of print]283(Pt 1): 137193

3D printed gelatin/PTMC core/shell scaffolds with NIR laser-tuned drug/biomolecule release for cancer therapy and uterine regeneration.

Shangsi Chen, Jiahui Lai, Jizhuo Chen, Liwu Zheng, Min Wang.

  Surgical resection is an efficient treatment for cancerous tissues and uterine fibroids in the women uterus. However, the insufficiency of clinical interventions could result in tumor recurrence, and the defective tissues remained would cause intrauterine adhesions (IUAs) and further affect reproduction capacity. In this study, 3D printed hydrogel/poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PTMC" in short) core/shell scaffolds with NIR-tuned doxorubicin hydrochloride (DOX) and estradiol (E2) dual release were designed and fabricated for cancer therapy and uterine regeneration. Gelatin (Gel) and DOX were homogeneously mixed and then 3D printed to form Gel-DOX scaffolds. Gel-DOX scaffolds were then immersed in PTMC-PDA@E2 solution to fabricate Gel-DOX/PTMC-PDA@E2 core/shell scaffolds. Consequently, Gel-DOX/PTMC-PDA@E2 scaffolds could release DOX and E2 in a chronological manner, firstly delivering DOX assisted by phototherapy (PTT) to effectively kill Hela cells and then sustainably releasing E2 to promote uterine tissue regeneration. In vitro experiments showed that core/shell scaffolds exhibited excellent anticancer efficiency through the synergy of DOX release and hyperthermia ablation. Moreover, E2 could be sustainably released for over 28 days in vitro to promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). The novel Gel-DOX/PTMC-PDA@E2 core/shell scaffolds have therefore exhibited potential promise for the treatment of cancer therapy and uterine regeneration.

Keywords:  3D printing; Cancer therapy; Core/shell scaffolds; Dual release; Uterine regeneration

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.137193
Biomed Mater. 2024 Nov 06.

4D printing of smart scaffolds for bone regeneration: a systematic review.

Niusha Gharehdaghi, Hanieh Nokhbatolfoghahaei, Arash Khojasteh.

   OBJECTIVE: As a novel emerging technology, four-dimensional (4D) printing allows 3D-printed materials to change over time. This systematic review is conducted to evaluate the purpose, materials, physiomechanical, and biological properties of 4D-printed scaffolds used for bone tissue engineering.Method and materials:An electronic search was conducted following the PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and Google Scholar online databases limited to English articles until April 2024. Studies in which scaffolds were fabricated through 3D printing methods responding to external stimulation were included. The quality of in vitro and in vivo studies was evaluated through the modified CONSORT checklist and SYRCLE's risk of bias tool.Results:The full text of 57 studies were reviewed, and 15 studies met the inclusion criteria. According to the analyzed studies, most scaffolds responded to temperature changes showing shape memory effect. Polyurethane (PU) and poly(lactic acid) (PLA) were the most common shape memory polymers, and the most common fabrication method used was Fused Deposition Modeling (FDM).Conclusion:A comprehensive systematic review of the studies from the past 10 years demonstrated several findings: 1) Shape memory, drug delivery, and shape morphing are three general purposes of 4D printing for bone regeneration. 2) Smart materials used for 4D printing mostly consist of shape memory polymers. 3) Temperature changes account for the majority of stimulation used for 4D printing. 4) incorporating 4D printing principles does not have a negative impact on the physiomechanical properties of the designed scaffold. 5) The 4D-printed scaffolds show a higher osteogenic differentiation capacity than their identical 3D-printed structures in terms of bone regeneration.&#xD.

Keywords:  4D printing; bone regeneration; drug delivery; shape memory; shape morphing; smart scaffold

DOI:  https://doi.org/10.1088/1748-605X/ad8f80
ACS Biomater Sci Eng. 2024 Nov 04.

Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.

Yunyang Li, Jingwen Wu, Peilin Ye, Yilin Cai, Mingfei Shao, Tong Zhang, Yanchuan Guo, Sujuan Zeng, Janak L Pathak.

  Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.

Keywords:  Biological materials; Bone tissue engineering; Decellularization extracellular matrix; Regenerative medicine

DOI:  https://doi.org/10.1021/acsbiomaterials.4c01764
Adv Healthc Mater. 2024 Nov 03. e2403613

Incorporating Hydrogel (with Low Polymeric Content) into 3D-Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects.

Rongpeng Dong, Mingyang Kang, Yang Qu, Tingting Hou, Jianwu Zhao, Xueliang Cheng.

  Treating large bone defects remains a considerable challenge for clinicians: bone repair requires scaffolds with mechanical properties and bioactivities. Herein, based on crosslinking o-phthalaldehyde (OPA) with amine groups, 4-arm polyethylene glycol (4armPEG)-OPA/Gelatin hydrogel loaded with bone morphogenetic protein 2 (BMP2) is prepared and a three dimensional (3D)-printed poly (lactic-co-glycolic acid) (PLGA) porous scaffold is filled with the hydrogel solution. The composite scaffold, with a compression modulus of 0.68 ± 0.097 GPa similar to the cancellous bone, has a porosity of 56.67 ± 4.72% and a pore size of about 380 µm, promoting bone growth. The hydrogel forms a porous network at low concentrations, aiding protein release and cell migration. The hydrogel degrades in approximately three weeks, and the scaffold takes five months, matching bone repair timelines. BMP2 release experiment shows a sustained BMP2 release with a 72.4 ± 0.53% release ratio. The ALP activity test and alizarin red staining shows effective osteogenic promotion, while RT-PCR confirms BMP2@Gel enhanced COL-1 and OPN expression. Animal experiments further validate the composite scaffold's bone repair efficacy. This study demonstrates the effectiveness of the hydrogel in releasing BMP2 and the mechanical support of the 3D-printed PLGA porous scaffold, providing a new treatment for bone defects.

Keywords:  BMP2; PLGA scaffold; bone repair; gelatin; o‐phthalaldehyde

DOI:  https://doi.org/10.1002/adhm.202403613