Algae are a group of autotrophic eukaryotic organisms. They can be classified as microalgae and macroalgae, and are found in marine and freshwater environments ( Borghans et al., 2008; Wang et al., 2017; Khan, Shin, and Kim, 2018; Sharma, Kanchi, and Bisetty, 2019). Algal extracts, such as polysaccharides, are frequently used as polymer binding agents in bone tissue engineering to promote tissue growth and proliferation because of their immunomodulatory, anti-inflammatory, antibacterial, and antioxidant activities ( Raposo et al., 2015; Barua et al., 2019; Nour et al., 2019).

Macro- and microalgae are the latest sources of macromolecules and their alternative derivatives, such as carotenoid molecules found in the Chlorophyceae family, which includes microalgae Dunaliella, Chlorella, Muriellopsis, Haematococcus, and Chlamydomonas spp. ( Berthon et al., 2017; Sayin et al., 2020; El-Chaghaby and Rashad, 2021). Furthermore, cyanobacteria also contain phycobiliproteins, accounting for 40% of these phycobiliproteins’ overall dissolved protein content ( El-Chaghaby and Rashad, 2021). Macromolecule polysaccharide derivatives include chitin, fucoidans, carrageenans, and alginate, which are abundant (up to 76% of dry weight) in macroalgae species, including Ulva, Ascophyllum, Palmaria, and Porphyra sp. ( Mallik et al., 2020; El-Chaghaby and Rashad, 2021). Macromolecules, especially collagen, are derived from algae and are generally complex macroproteins that comprise 20%–30% of all proteins found in living organisms ( Coppola et al., 2020; Joyce et al., 2021) and represent the extracellular matrix’s main structural component in all connective and interstitial tissues of the parenchymal organs ( Kim et al., 2020; Srivastava, 2022).

Collagen is well known for its uniqueness as a structural support for biomedical applications such as skin implants, medicines, cosmetics, the leather and film industries, diagnostic imaging, and therapeutic delivery ( Coppola et al., 2020). Collagen can be used in various applications due to its excellent biocompatibility and degradability ( Zhao et al., 2013; Wahyudi et al., 2016; Felician et al., 2018). In addition, collagen and macromolecules derived from natural biomaterials have weak immunogenicity, reducing rejection risk when ingested or injected (implanted) into different body parts ( Coppola et al., 2020). Historically, most of the available collagen was extracted from the waste of the cattle and pig processing industries ( Matinong et al., 2022). Nevertheless, over recent decades, the use of macromolecules derived from these sources has been restricted and prohibited ( Gómez-Guillén et al., 2011; Coppola et al., 2020). This ban may be attributed to reasons such as the religious restrictions of Islam, Hindu, and Judaism, who account for 38.4% of the world’s population, and the possibility of being a disease transmission route ( Coppola et al., 2020).

The current needs of tissue engineering products have not been met as there is a challenge in developing ideal materials for bone and cardiovascular tissue regeneration. Therefore, this issue emphasizes the importance of using algae as a source of macromolecules used in the biomedical field, both now and in the future. With advances in biological science and cutting-edge technology, particularly in biosynthesis and synthetic biology, algal-derived macromolecules can be used in biomedical applications using synthetic biology, transforming their chitin derivatives into biomaterials ( Dyo and Purton, 2018). This natural biomaterial has been successfully used in biomedicine for various procedures (e.g., wound healing, bone repair, cell scaffolding, antimicrobial, hemostasis, and cartilage repair; Brovold et al., 2018), devices (e.g., composite heart valve material; Rastogi and Kandasubramanian, 2019), cardiovascular applications ( Benko et al., 2022), and biological processes (e.g., photoelectricity, electrocatalysis, and adsorption; Bi et al., 2021). In addition to examining the most recent advancements in the biosynthesis of algal-derived biomaterials, this review aims to interpret the most recent findings regarding its potential application in bone and cardiovascular tissue engineering. Furthermore, the topics in this review have not yet been covered extensively in the literature.

The stability and nondegradable properties of synthetic polymers have recently caused the deterioration of environmental quality and highlighted the need for developing bio-based polymers, especially for biomedical purposes ( Deng et al., 2021; Cywar et al., 2022). As stated in the Introduction, algae are a potential source of macromolecules and their derivatives are a potential use as biopolymers in biomedicine. The advantages of using algae over other feedstocks for sustainability and the environment are that they have a faster growth rate, resulting in more biomass, act as environmental bioremediators, and are valuable biofuel feedstocks ( Banerjee, Singh and Shukla, 2016; Nasr et al., 2020).

Bar-Shai et al. (2021) successfully analyzed the biocompatibility of cellulose derived from two macroalgae seaweeds, Cladophora sp . and Ulva sp. Sargassum cristaefolium (brown macroalgae; Giriwono et al., 2019; Prasedya et al., 2019). In addition, red ( Galaxaura oblongata, Corallina elongate, and Cystoseria compressa) and brown ( C. compressa and Sargassum vulgare) algae powders have been successfully used and incorporated into polyhydroxyalkanoates, polycaprolactone, and polylactide to make potential biomaterials for the biomedical field ( Sayin et al., 2020). They included Caulerpa racemosa, which has collagen properties, according to the latest study ( Permatasari et al., 2022). Interestingly, polysaccharide derivatives or potential biopolymers such as chitin, fucoidans, sulfated fucans, sulfated l-fucose polysaccharide, carrageenans, sulfated galactan, laminaran, and alginate are abundant, even reaching 76% of the dry weight contained in macroalgae, mainly the Ulva, Ascophyllum, Palmaria, and Porphyra species ( Zia et al., 2017; Azeem et al., 2017; El-Chaghaby and Rashad, 2021).

In addition to macroalgae, microalgae have great potential as a source of macromolecules and their derivatives, albeit to a lesser extent. Among the microalgae known as superfoods, Spirulina sp. contains type II collagen ( Darvin et al., 2015; Elbialy et al., 2021; Sonawane et al., 2022) and nanostructured or nanofiber scaffold properties ( Morais et al., 2014; Moreira et al., 2021; McCauley et al., 2022). In addition, microalgae of the Chlorophyceae family, such as Dunaliella, Chlorella, Muriellopsis, Haematococcus, and Chlamydomonas spp., contain abundant carotenoid derivatives ( Berthon et al., 2017; Sayin et al., 2020; El-Chaghaby and Rashad, 2021). Spirulina also contains phycobiliproteins, which comprise 40% of these phycobiliproteins’ overall dissolved protein content ( El-Chaghaby and Rashad, 2021), with promising potential as multifunctional biomaterial scaffolds ( Pereira and Rodrigues, 2021). The following section elaborates on using algal-derived biomaterials.

The exciting potential of biomaterials from algae macromolecules and their derivatives has been previously shown. Furthermore, the upcoming section discusses their potential applications in the biomedical field, especially in bone and cardiovascular tissue ( Table 1). Tissue engineering is a biomedical engineering discipline that uses the appropriate combination of cells, techniques, material methods, and biochemical and physicochemical factors to restore, maintain, enhance, or replace various biological tissue types through biosynthesis or synthetic biology ( Li et al., 2018).

The multipotentiality of algae as biomaterials in bone and cardiovascular tissue engineering will face many challenges. First, plant-based molecules or natural macromolecules (mainly algae) encourage body tissues to synthesize macromolecules by providing the required substances. However, the question arises about algal macromolecule bioavailability and yield. Gao et al. (2013) highlighted the crucial roles of nanotechnology and nanocomposite applications in modifying macromolecules. Using nanotechnology with its improved surface-to-area volume ratio may address the low quantity of collagen extracted from algae ( Mokhena et al., 2020; Lo and Fauzi, 2021). Using in vitro models or bioreactors was encouraged for research translation since the variables, composition, and target populations can be controlled and adjusted before continuing to preclinical or clinical trials ( Stassen et al., 2017; Mobini et al., 2019). However, the fabrication processes significantly impact the properties of marine macromolecule-based structures, such as mechanical properties, internal pore size and structure, cell encapsulation, degradation rate, and incorporation of bio-additives into the scaffolds ( Liu et al., 2022). The lower denaturation temperature of marine collagen, especially from algae, is a significant drawback since it impacts both the processing environment and the scaffold properties in vitro and in vivo ( Shahidi et al., 2019; Akita et al., 2020). Iravani and Soufi (2021) also mentioned that the clinical use of scaffolds for tissue engineering applications still faces many complex problems, such as donor-site morbidity, a lack of resilience and mechanical strength, consistent volume loss, and fibrous capsular structure.

In addition, using algae as natural biomaterials also faces several challenges due to limited available studies. To fully benefit from algae in emergency medicine fields, such as orthopedic trauma and cardiovascular damage, a solid guideline regarding the use and manufacture of these products needs to be established ( Vunjak-Novakovic et al., 2010; Lee and Mooney, 2012; Łabowska et al., 2020). The establishment of the guidelines is a crucial step so that the other factors in using algae, such as the products’ optical features, emission color control, and other standards, can be met to maximize their benefits ( Deng, Ngo, and Guo, 2022; Fernandes et al., 2022). In the face of such challenges, more clinical trials are needed to gather sufficient data to identify the optimal method for manufacturing algae-derived macromolecules for biomedical field applications. After such guidelines have been established, more experiments in clinical settings must be conducted. Most studies in this field have presented laboratory-level evidence, with only a few performed in clinical settings ( Ewers, 2005; Taemeh et al., 2020; Wang, Chen, and Zhang, 2021; Akimoto et al., 2022). Since existing technologies, such as magnetic resonance imaging and other modalities, could be used to monitor new tissue development from algal-derived macromolecules, the successes of such experiments will contribute little to forming conclusions about the benefit of such therapies due to the nature of in vivo studies using experimental animals instead of human subjects ( Kotecha et al., 2017).

Moreover, adverse algal-derived macromolecule effects must also be considered and researched thoroughly to identify potential failures of such use ( Hickman et al., 2018; Iravani and Varma, 2022). There is no doubt about the functions and benefits of macroalgae and microalgae, even though research is still needed to determine their usefulness and safety in human-based settings. However, this does not reduce the possible use of algal-derived macromolecules in biomedical settings, especially tissue dressings ( McCauley et al., 2022). All limitations exist mainly due to the lack of proper techniques and guidelines, human research, and funding. Such studies will increase in frequency and quality provided the benefit of micro- and macro-algae continues to be researched thoroughly ( De Anda-Flores et al., 2022).

Previous reports have used synthetic biology to show that algae rich in macromolecules and their derivatives have potential biomedical applications in bone and cardiovascular tissue engineering ( Figure 1). Algae use benefits from lower immunogenicity, reducing rejection risk when ingested (implanted) into different body parts ( Coppola et al., 2020). As illustrated in Figure 1, biomaterials derived from algae macromolecules have been successfully used in various biomedical fields, such as wound healing, bone repair, cell scaffolding, cartilage repair, heart valve composite materials, and other cardiovascular uses ( Bi et al., 2021).

The problems in using such products arise from the lack of effective guidelines, human trials, and funding to perform the required research. Therefore, we encourage more studies on algal-derived macromolecules with a broader biomedical scope that can provide the latest innovations in their use. More in-depth research using a nanotechnology approach is needed to explore the potential of algae macromolecules as natural biomaterial scaffolds for medical applications due to their properties and benefits that will bring future developments in the medical field.