The rs6427384 and rs6692977 Single Nucleotide Polymorphisms of the Fc Receptor-Like 5 (FCRL5) Gene and the Risk of Ankylosing Spondylitis: A Case Control Study in a Single Center in China.

BACKGROUND The study aimed to explore the genetic association of Fc receptor-like 5 (FCRL5) gene variants (rs6427384 and rs6692977) with ankylosing spondylitis risk in Chinese Han population. MATERIAL AND METHODS Genotyping for FCRL5 gene variations rs6427384 and rs6692977 was implemented among 130 ankylosing spondylitis cases and 135 healthy persons, through polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Frequency dissimilarity for 2 polymorphisms was compared between 2 groups using chi-square test. The association strength of FCRL5 gene polymorphism with ankylosing spondylitis risk was estimated by odds ratios with 95% confidence intervals. RESULTS The frequencies of rs6427384 CC genotype and C allele were significantly lower in the case group than that in the control group (P<0.05), which suggested that C allele of rs6427384 polymorphism might offer protection against ankylosing spondylitis onset. Whereas only 2 genotypes of rs6692977 were detected in the control group, and no significant association was found with ankylosing spondylitis susceptibility. CONCLUSIONS FCRL5 gene polymorphism rs6427384 was correlated to ankylosing spondylitis occurrence among Chinese Han population, while rs6692977 was not.

Superhydrophobic Polyhydroxyalkanoates: Preparation and Applications.

Poly( R-3-hydroxybutyrate- co- R-3-hydroxyhexanoate) (PHBHHx), a family member of microbial polyhydroxyalkanoates (PHA), is a biodegradable and biocompatible material with some hydrophobicity and reasonable strength for packaging and tissue engineering applications. In this study, superhydrophobic PHBHHx is fabricated via a simple nonsolvent-assisted process. The material can absorb all tested hydrophobic solvents and oil up to 6-fold of the material weights from water, permitting applications for cleaning environmental oil or solvent pollutions with convenience of disposal after the usage due to its biodegradability. With an excellent combination of biodegradability and biocompatibility, superhydrophobic PHBHHx films are evaluated for antibioadhesion properities to exploit possible implant usages. Up to 100% reductions for platelet adhesions on the superhydrophobic PHBHHx surfaces are observed compared with that on the control material surfaces. Superhydrophobic biodegradable and biocompatible PHBHHx films demonstrate promising low value and high volume or high value and low volume applications.

Highly Efficient Fluorescent Material Based on Rare-Earth-Modified Polyhydroxyalkanoates.

Fluorescent materials play an important role in biomedical fields. However, the main types of fluorescent materials suffer from several disadvantages especially the biotoxicity, which largely restrict its wider applications in biological fields. In this study, a highly efficient rare-earth-modified fluorescent material was successfully designed and fabricated based on polyhydroxyalkanoates, which are known as biodegradable and biocompatible materials. A new Functional-PHA polymer was microbially synthesized by engineered Halomonas bluephagenesis and was used as a basal matrix to generate the rare-earth-modified PHA. N-Acetyl-l-cysteine-grafted PHA (NAL-grafted-PHA) was first produced via a UV-initiated thiol-ene click reaction and the rare earth metal ions (Eu3+ and Tb3+) were subsequently chelated onto the NAL-grafted-PHA through the coordination effect. The composite material exhibited intense photoluminescence properties under UV laser excitation, indicating the excellent features as fluorescent material. The enhanced hydrophilicity and superior biocompatibility of rare-earth-chelated PHA were confirmed, suggesting its great potential application value in biomedical fields.

Synthesis, Characterization and Application of Thermoresponsive Polyhydroxyalkanoate-graft-Poly(N-isopropylacrylamide).

A thermoresponsive graft copolymer polyhydroxyalkanoate-g-poly(N-isopropylacrylamide) or short as PHA-g-PNIPAm, was successfully synthesized via a three-step reaction. First, PNIPAm oligomer with a trithiocarbonate-based chain transfer agent (CTA), short as PNIPAm-CTA, with designed polymerization degree was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the PNIPAm-CTA was treated with n-butylamine for aminolysis in order to obtain a pendant thiol group at the end of the chain (PNIPAm-SH). Finally, the PNIPAm-SH was grafted onto unsaturated P(3HDD-co-3H10U), a random copolymer of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-10-undecylenate (3H10U), via a thiol-ene click reaction. Enhanced hydrophilicity and thermoresponsive property of the resulted PHA-g-PNIPAm were confirmed by water contact angle studies. The biocompatibility of PHA-g-PNIPAm was comparable to poly-3-hydroxybutyrate (PHB). The graft copolymer PHA-g-PNIPAm based on biopolyester PHA could be a promising material for biomedical applications.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles.

Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100-200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.

Recent advances of medical polyhydroxyalkanoates in musculoskeletal system.

Infection and rejection in musculoskeletal trauma often pose challenges for natural healing, prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution. Polyhydroxyalkanoates (PHAs) are a large family of biopolyesters synthesised in microorganism, demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery. With different monomer-combination and polymer-types, multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching, compression, twist in long time, especially in musculoskeletal tissue engineering. This review systematically summarises the applications of PHAs in multiple tissues repair and drug release, encompassing areas such as bone, cartilage, joint, skin, tendons, ligament, cardiovascular tissue, and nervous tissue. It also discusses challenges encountered in their application, including high production costs, potential cytotoxicity, and uncontrollable particle size distribution. In conclusion, PHAs offer a compelling avenue for musculoskeletal system applications, striking a balance between biocompatibility and mechanical performance. However, addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Transient embolization with microspheres of polyhydroxyalkanoate renders efficient adenoviral transduction of pancreatic capillary in vivo.

BACKGROUND: Our previous study showed an efficient targeting of islets of Langerhans by adenoviral injection via the celiac trunk. Unexpectedly, none of the endothelial cells was infected given the direct contact between adenoviruses and the capillary wall. The present study intended to provide an efficient approach for adenoviral targeting of the microcapillary endothelial cells in the pancreas. METHODS: We prepared microspheres of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with a size comparable to the diameter of capillary (5-10 µm). Scanning electron microscopy was applied to verify that adenoviruses carrying a green fluorescence protein gene were complexed with PHBHHx-microspheres after 30 min of co-incubation. The complexes were then injected into the pancreas of mice via the celiac trunk. RESULTS: Approximately 40% of endothelial cells in the pancreas were labeled 5 days after surgery. Islet cells were labeled occasionally, whereas labeling of the acinar and ductal tissues was barely detectable. Endothelium targeting was inefficient in other internal organs. Consistent with the reported superior tissue compatibility of PHBHHx, no discernable microspheres were found in all of the organs examined. Furthermore, splenocyte activation was dampened when adenoviruses were complexed with the microspheres. CONCLUSIONS: The present study has established an approach for efficient pancreatic capillary targeting by using microsphere-adenoviral complexes. This procedure could be invaluable for the treatment of capillary-related diseases.

Advances in modified hyaluronic acid-based hydrogels for skin wound healing.

Hyaluronic acid (HA) is a natural linear anionic polysaccharide with many unique characteristics such as excellent biocompatibility and biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity. HA plays crucial roles in numerous biological processes, including the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. All these properties and biological functions of HA make it an appealing material for the synthesis of biomedical hydrogels for skin wound healing. Since HA is not able to be gelate alone, it must be processed and functionalized through chemical modifications and crosslinking to generate versatile HA-based hydrogels. In recent years, different physical and chemical crosslinking strategies for HA-based hydrogels have been developed and designed, such as radical polymerization, Schiff-base crosslinking, enzymatic crosslinking, and dynamic covalent crosslinking, and they have broad and promising applications in skin wound healing and tissue engineering. In this review, we focus on chemical modification and crosslinking strategies for HA-based hydrogels, aiming to provide an overview of the latest advances in the development of HA-based hydrogels for skin wound healing. We summarize and propose feasible measures for the application of HA-based hydrogels for skin treatment, and discuss future application trends, which may ultimately promote HA-based hydrogels as a promising biomaterial for clinical applications.

Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant.

PhaP or phasin is an amphiphilic protein located on surfaces of microbial storage polyhydroxyalkanoates granules. This study aimed to explore amphiphilic properties of PhaP for possible application as a protein surfactant. Following agents were used to conduct this study as controls including bovine serum albumin, sodium dodecyl sulfate (SDS), Tween 20, sodium oleate, a commercial liquefied detergent together with the same amount of PhaP. Among all these tested control surfactants, PhaP showed the strongest effect to form emulsions with lubricating oil, diesel, and soybean oil, respectively. PhaP emulsion stability study compared with SDS revealed that PhaP had a stronger capability to maintain a very stable emulsion layer after 30 days while SDS lost half and two-thirds of its capacity after 2 and 30 days, respectively. When PhaP was more than 200 µg/ml in the water, all liquids started to exhibit stable emulsion layers. Similar to SDS, PhaP significantly reduced the water contact angles of water on a hydrophobic film of biaxially oriented polypropylene. PhaP was thermally very stable, it showed ability to form emulsion and to bind to the surface of polyhydroxybutyrate nanoparticles after a 60- min heating process at 95 °C. It is therefore concluded that PhaP is a protein with thermally stable property for application as natural and environmentally friendly surfactant for food, cosmetic, and pharmaceutical usages.

Fenton Reaction Induced by Fe-Based Nanoparticles for Tumor Therapy.

Fenton reaction, a typical inorganic reaction, is broadly utilized in the field of wastewater treatment. Recently In case of its ability to inhibit the growth of cancer cells, it has been frequently reported in cancer treatment. Using the unique tumor microenvironment in cancer cells, many iron-based nanoparticles have been developed to release iron ions in cancer cells to induce Fenton reaction. In this mini review, we outline several different types of iron-based nanoparticles and several main means to enhance Fenton reaction in cancer cells. Finally, we discussed the advantages and disadvantages of iron-based nanoparticles for cancer therapy, prospected the future development of iron-based nanoparticles. It is believed that iron-based nanoparticles can make certain contribution to the cause of human cancer in the future.

Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity.

An efficient long-term intracellular growth factor release system in simulated microgravity for osteogenic differentiation was prepared based on polylactic acid (PLA) and polyhydroxyalkanoate (PHA) nanoparticles (NPs) for loading of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 7 (BMP7) (defined as sB2-PLA-NPs and sB7-PHA-NPs), respectively, associated with osteogenic differentiation of human adipose derived stem cells (hADSCs). On account of soybean lecithin (SL) as biosurfactants, sB2-PLA-NPs and sB7-PHA-NPs had a high encapsulation efficiency (>80%) of BMPs and uniform small size (<100 nm), and showed a different slow-release to provide BMP2 in early stage and BMP7 in late stages of osteogenic differentiation within 20 d, due to degradation rate of PLA and PHA in cells. After uptake into hADSCs, by comparison with single sB2-PLA-NPs or sB7-PHA-NPs, the Mixture NPs compound of sB2-PLA-NP and sB7-PHA-NP with a mass ratio of 1:1, can well-promote ALP activity, expression of OPN and upregulated related osteo-genes. Directed osteo-differentiation of mixture NPs was similar to result of sustained free-BMP2 and BMP7-supplying (sFree-B2&B7) in simulated microgravity, which demonstrated the reliability and stability of Mixture NPs as a long-term osteogenic differentiation system in space medicine and biology in future.

Advances in the design and development of SARS-CoV-2 vaccines.

Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials.

Injectable, Intrinsically Antibacterial Conductive Hydrogels with Self-Healing and pH Stimulus Responsiveness for Epidermal Sensors and Wound Healing.

Torealize intelligent and personalized medicine, it is a huge challenge to develop a hydrogel dressing that can be used as a sensor to monitor human health in real-time while promoting wound healing. Herein, an injectable, self-healing, and conductive chitosan-based (CPT) hydrogel with pH responsiveness and intrinsic antibacterial properties was fabricated via a Schiff base linkage and a hydrogen bond. Due to the introduction of Schiff base bonds, the injectable CPT hydrogel exhibits various excellent properties, such as pH responsiveness to sol-gel transition, self-healing properties, and broad-spectrum antibacterial properties even without additional antibacterial agents. In vitro experiments verify the excellent biocompatibility of the as-prepared hydrogel. An in vivo experiment in a mouse full-thickness skin-wound model was performed to confirm the outstanding effect on wound healing. Meanwhile, as epidermal sensors, the conductive hydrogel that perceives various human activities in real-time could provide the real-time analysis of the patient's healthcare information. Based on these excellent properties, the CPT hydrogel, as a biological dressing with a sensing function, lays a solid foundation for the further realization of personalized medicine.

3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration.

Hydrophilic bone morphogenetic protein 2 (BMP2) is easily degraded and difficult to load onto hydrophobic carrier materials, which limits the application of polyester materials in bone tissue engineering. Based on soybean-lecithin as an adjuvant biosurfactant, we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone) and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction, avoiding the use of exogenous cells. The optimized bioactive osteo-polyester scaffold (BOPSC), i.e. SBMP-10SC, had a high BMP2 entrapment efficiency of 95.35%. Due to its higher porosity of 83.42%, higher water uptake ratio of 850%, and sustained BMP2 release with polymer degradation, BOPSCs were demonstrated to support excellent in vitro capture, proliferation, migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells (mADSCs), and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds (10SCs). Furthermore, in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells, which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months. The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.

Marine-Derived Collagen as Biomaterials for Human Health.

Collagen is a kind of biocompatible protein material, which is widely used in medical tissue engineering, drug delivery, cosmetics, food and other fields. Because of its wide source, low extraction cost and good physical and chemical properties, it has attracted the attention of many researchers in recent years. However, the application of collagen derived from terrestrial organisms is limited due to the existence of diseases, religious beliefs and other problems. Therefore, exploring a wider range of sources of collagen has become one of the main topics for researchers. Marine-derived collagen (MDC) stands out because it comes from a variety of sources and avoids issues such as religion. On the one hand, this paper summarized the sources, extraction methods and characteristics of MDC, and on the other hand, it summarized the application of MDC in the above fields. And on the basis of the review, we found that MDC can not only be extracted from marine organisms, but also from the wastes of some marine organisms, such as fish scales. This makes further use of seafood resources and increases the application prospect of MDC.

An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells.

In contrast to the early acting bone morphogenetic protein 2, bone morphogenetic protein 7 (BMP7) plays a decisive role mainly in the late stages of bone formation. To overcome deactivation and degradation of expensive BMP7, we designed a novel long-acting BMP7 release system based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) nanoparticles to enable the induction of osteogenic differentiation in human adipose mesenchymal stem cells (ADSCs). In order to improve the encapsulation efficiency of BMP7 and avoid damage by organic solvents, BMP7 was modified and protected using the biosurfactant soybean lecithin. In an in vitro test, BMP7-soybean lecithin-P34HB nanoparticles (BMP7-SPNPs) showed a short initial burst of BMP7 release during the first 24h, followed by a steady increase to a cumulative 80% release in 20days. Compared with the rapid release of control P34HB nanoparticles without soybean phospholipids loaded with BMP7 without soybean lecithin, BMP7-SPNPs significantly reduced the initial burst of BMP7 release and stabilized the content of BMP7 to allow long-term osteogenic differentiation during the late phase of bone development. Human ADSCs treated with BMP7-SPNPs showed higher alkaline phosphatase activity and higher expression levels of genetic markers of osteogenic differentiation compared with the control group. Thus, the results indicate that BMP7-SPNPs can be used as a rapid and long-acting BMP7 delivery system for osteogenic differentiation.

A Micro-Ark for Cells: Highly Open Porous Polyhydroxyalkanoate Microspheres as Injectable Scaffolds for Tissue Regeneration.

To avoid large open surgery using scaffold transplants, small-sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300-360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10-60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast-regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier-free hMSCs in an ectopic bone-formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro-Noah's Ark to safely transport cells to a defect tissue.